Dept of Paediatrics & Adolescent Med

DEPT OF PAEDIATRICS & ADOLESCENT MED

Researcher : Au KY

List of Research Outputs

Au K.Y., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV TAT modulation of IFN-g induced expression of autophagy-associated genes in primary human blood macrophages., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV Tat modulation of IFN- γ-induction of autophagy-associated genes in primary human blood macrophages., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. December 2-3. 2009.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV Tat modulation of IFN-γ-induced expression of autophagy-associated genes in primary human blood macrophages., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-095]. 2009.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., Travel Award, 2010 Annual General Meeting and Scientific Meeting, Hong Kong Society for Immunology, Hong Kong, April 17, 2010 . 2010.

Researcher : Bhatia I

List of Research Outputs

Bhatia I., Tsim K.W. and Cheung P.T., Methyl mercury induced epigenetic dysregulation of BDNF gene in NG108 cells in vitro – a possible mechanism of environment-epigenome interactions underlying neuropsychiatric and neurodevelopmental disorders., 4th Asian Epigenomics Meeting. Singapore Augst 24th -25th, 2009.. 2009.

Researcher : But BWM

List of Research Outputs

Huen K.F., Low L.C.K., Cheung P.T., Wong G.W.K., But B.W.M., Kwan E.Y.W., Lam Y.Y., Lee C.Y., Wong L.M., Ng K.L., Cheng A.W.F., Tong C.T. and Wong W.H.S., An Update on the Epidemiology of Childhood Diabetes in Hong Kong , Hong Kong Journal of Paediatrics . 2009, 14: 252-259.

Researcher : Chan GCF

Project Title:	Review of local experience in the management of childhood myelodysplastic syndrome
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/2001

Abstract:

To study the local incidence and outcome of this rare type of childhood maliquancy.

Project Title:	Treatment protocol for childhood medulloblastoma in Hong Kong
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/2001

Abstract:

To study the treatment outcome of this most common form of childhood brain tumour in Hong Kong.

Project Title:	Survey on the prevalence on use of alternative medical treatment in paediatric patients
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	09/2001

Abstract:

To study the prevalence, pattern of usage and the underlying predisposing factors on the use of alternative medicine in children.

Project Title:	Direct generation and functional characterization of human dendritic cells derived from bone marrow cells of leukemic origins
Investigator(s):	Chan GCF, Chiu CSW, Ma ESK, Huang F
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	07/2002

Abstract:

To determine the implication of dentritic cells generated from leukaemic cellls on the host immune system.

Project Title:	The In-vitro Effect of SDF-1 & IFN-gamma on Migration and Survival of Mesenchymal Stem Cells
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2009
Completion Date:	03/2010

Abstract:

Mesenchymal stem cells (MSCs) are multi-potent cells which under appropriate conditions can differentiate into a variety of tissues. MSCs differ from other types of stem cells by their unique immuno-modulatory property which may suppress cellular immune response to dendritic cells, T cells and NK cells. MSCs are also immunologically neutral towards HLA histocompatibility and therefore can be introduced as heterologous graft without eliciting rejection or host versus graft response. Presently, human MSCs has been used as an adjunct to cell/tissue transplantation (e.g. bone marrow cells) to suppress graft vs host reaction or short-term treatment of refractory autoimmune disorders. It has been shown that both human and murine MSCs can migrate to site of inflammation and exert immunosuppressive action even though if it is given intravenously. However, the life span of these MSCs appears to be short. What accounts for the unique migratory or chemotactic behavior and reduced life span in-vivo remained uncertain. The current postulation is that the migration is induced by certain soluble factors such as growth factors or chemokines. Among different factors possibly involved, stromal cell derived factor (SDF-1) is one of the possible candidates. SDF-1 plays a key role in the migration of both hematopoietic and non-hematopoietic cells via a receptor CXCR4. SDF-1 can protect the migrating cells against the apoptosis induced by “anoikis” stress. Anoikis is a kind of apoptosis which occurs when adherent cells are detached from their extracellular matrix. On the other hand, some data suggested that the expression of CXCR4 can be down-regulated by interferon gamma (IFN-r), an inflammatory cytokines. How these soluble factors interact with each other, especially on the migration and survival of MSCs, remains unknown. Objective: We would like to delineate the regulatory mechanisms involved in human MSCs migration and survival during systemic administration, in particularly related to the actions of SDF-1 & IFN-r. The findings can guide our clinical applications of MSCs in the area of tissue repair and immuno-modulation for autoimmune diseases. Hypothesis: We postulate that SDF-1 & IFN-r interacts with each other in a counter-balancing manner in regulating the migration and survival of non-adherent MSCs. IFN-r will suppress both the SDF-1 driven migration and survival against anoikis stress. Such changes will subsequently result in shorter survival of MSCs in inflammatory environment. We will perform our experiments following the order below: • Aim 1: SDF-1 can enhance human MSCs’ migration and survival under anoikis stress • Aim 2: IFN-r can suppress the effect of SDF-1 in hMSCs leading to poorer migration and survival under anoikis stress

Project Title:	King's/HKU Fellowship Awards 2009-10
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	King's/HKU Fellowship Awards
Start Date:	09/2009

Abstract:

To visit the Department of Medical and Molecular Genetics in King's College London to acquire knowledge and technique in inducing conditionally immortalized clonal stem cell lines under the ex-vivo culture environment, and to learn about the latest progress on gene therapy for beta-thalassaemia and other monogenic disorders.

Project Title:	41th Congress of the International Society of Paediatric Oncology (SIOP) Vincristine but not imatinib could suppress mesenchymal niche's support to acute lymphoid leukemic (ALL) cells Treatment outcome of metastatic neuroblastoma with antiganglioside 2 monoclonal antibody (3F8): the Hong Kong experience
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2009
Completion Date:	10/2009

Abstract:

N/A

Project Title:	Suppression on Mesenchymal Stromal Cells Function Can Reduce the Migration & Invasion Potentials of the Neuroblastoma Cells
Investigator(s):	Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	01/2010

Abstract:

Objective: We will test the hypothesis that with effective suppression of hMSCs, we can reduce the metastatic potential of neuroblstoma cells. Hypothesis: We postulate that MSCs can enhance the migration and invasion of neuroblastoma cells. By effectively suppress the hMSCs function, we can reduce the metastatic potential of neuroblastoma cells. We will perform our experiments following the order below: • Aim 1: hMSCs can enhance the migration and invasion of neuroblastoma cells • Aim 2: Inhibitors of hMSCs can overcome the enhancing effects of hMSCs on neuroblastoma

List of Research Outputs

Chan B.P., Hui T.Y., Wong M.Y. and Chan G.C.F., Formation of injectable and osteoinductive bone-like microparticles using mesenchymal stem cell-collagen microspheres., 7th Annual Meeting of International Society for Stem Cell Research, Jul 8-11, 2009. Barcelona, Spain.. 2009, 1263.

Chan B.P., Wong H.L., Wong M.Y., Chan G.C.F. and Yang Z., Methods to Enhance Mesenchymal Stem Cell Migration, Provisional Patent Application (filed on 15 June 2010) (Application No. 61/354,871). 2010.

Chan G.C.F., 兒童腦腫瘤非不治之症, 2nd Health Education Booklet with Metro Daily, LKS Faculty of Medicine, HKU. 2010.

Chan G.C.F., Shing M.M.K., Luk C.W., Li R.C.H., Ling S.C., Li C.K. and Ha S.Y., Characteristics and outcome of metastatic infant neuroblastoma. (oral presentation), Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association Ltd. 28 November . 2009.

Chan G.C.F., Childhood brain tumors: The puzzles, pitfalls and doubts., Scientific Meeting of Macau Pediatric Society, Macau. December 12. 2009.

Chan G.C.F., Childhood brain tumors: Challenge beyond the cure., HK Child Neurology and Developmental Paediatrics Bimonthly Meeting. May 13, . 2010.

Chan G.C.F., Classification and management of childhhod haemangioma. , Paediatric Haematology & Oncology Workshop, Princess Margaret Hospital. June 14, . 2010.

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (Deferoxamine, deferiprone and deferasirox) on the growth of klebsiella pneumoniae and aeromonas hydrophila isolated from transfusion-dependent thalassaemia patients., Hemoglobin (Proceedings of the 17th International Conference on Chelation (ICOC), Shenzhen, PR China 23-27 November 2007). 2009, 33(5): 352-360.

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (Desferal, Deferiprone & Deferaairox) on the growth of klebsiella and aeromonas isolated from transfusion dependent thalassaemia patients., Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association Ltd. 28 November. 2009.

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (desferal, deferiprone & deferasirox) on the growth of Klebsiella and Aeromonas isolated from transfusion dependent thalassemia patients., Hemoglobin. 2009, 33(5): 352-360.

Chan G.C.F., Effects of iron overload on dendritic cells differentiation and function. (oral presentation), Asia-Pacific Iron Academy Conference-2009 (APIA), Chiang Mai, Thailand, 27-29 November . 2009.

Chan G.C.F., Shing M.M.K., Yuen H.L., Lee A.C.W., Li C.K., Luk C.W., Ha S.Y. and Li C.K., Epidemiology & treatment outcome of childhood ependymoma in Hong Kong: Report from the Hong Kong Pediatric Hematology Oncology Study Group., Joint Annual Scientific meeting of the Hong Kong Paediatric Society & Hong Kong Paediatric Nurses Association Ltd. Nov 13, . 2009.

Chan G.C.F., Evaluation of iron contents in the brain of beta-thalassaemia major patients by susceptibility weighted imaging (SWI). (oral presentation), Asia-Pacific Iron Academy Conference-2009 (APIA), Chiang Mai, Thailand, 27-29 November . 2009.

Chan G.C.F., Long term survivors of AML/ALL. , The 39th Philippines Society of Hematology and Blood Transfusion Annual Convention, Manila, Philippines, Sept 14-16, 2009.. 2009.

Chan G.C.F., Managing terminal symptoms in children with cancers., The Annual Scientific Meeting of the Hong Kong Palliative Medicine Society. July 12, 2009 (Symposium Lecture) . 2009.

Chan G.C.F., Managing terminal symptoms of children with cancer., 6th Hong Kong Palliative Care Symposium. July 4, 2009. (Plenary Lecture). 2009.

Chan G.C.F., Medical treatment of childhood haemangioma. , Joint Annual Scientific Meeting of Hong Kong Dermatology Society & Hong Kong Plastic Surgery Society 2010. May 16, . 2010.

Chan G.C.F., Mesenchymal stem cell and cancer., The 5th Workshop of Asian Hematology, November 24. 2009.

Chan G.C.F., Molecular cytogenetics for diagnosis and risk classification of leukemia., The 39th Philippines Society of Hematology and Blood Transfusion Annual Convention, Manila, Philippines, Sept 14-16, 2009. . 2009.

Chan G.C.F., Palliative care: management of difficult symptoms., The 39th Philippines Society of Hematology and Blood Transfusion Annual Convention, Manila, Philippines, Sept 14-16, 2009.. 2009.

Chan G.C.F., Recent advances in the management of childhood neuroblastoma, The 6th Chinese Conference on Oncology & 9th Cross Strait Academic Conference on Oncology. Shanghai, China. May 20-23, 2010. (Plenary Lecture). 2010.

Chan G.C.F., Recent advances in the management of pediatric brain tumours., Annual Workshop on Pediatric Oncology, Shanghai, China. Oct 13, 2009 (Symposium Lecture). 2009.

Chan G.C.F., SIOP Award, International Society of Pediatric Oncology. 2009.

Chan G.C.F., Stem Cells Therapy Update: Diseases & Disabilities It Can Treat, CME Lecture of the 40th UERMMMC Alumni Homecoming. Manila, Philippines. Feb 2-5, . 2010.

Chan G.C.F., Supplement for immune enhancement in hematologic malignancies., American Society of Hematology (ASH) Annual Meeting 2009, New Orleans, USA, Dec 5-8, 2009. (Education Program). 2009.

Chan G.C.F., The Role of Traditional Chinese Medicine (TCM) in Immunology & Cancer., International Seminar on Herbal Drug Research, Present & Future Prospects. Tamlinadu, India, Dec 4-5, 2009 (Plenary Lecture). 2009.

Chan G.C.F., The effect of herbal extracts/-glucan on immune and cancer cells.b, International Seminar on Herbal Drug Research: Present and Future Prospects, Rocklands, Ooty, Tamil Nnadu, India. Oct 4-5. 2009.

Chan G.C.F., The good and bad effects of lingzhi related products in cancer., 靈芝產品治癌效用兩面睇, Public Lecture on the theme of Chinese Medicine Treatment for Cancer: Evidence and Practice, LKS Faculty of Medicine, HKU.. 中醫藥治癌: 剖證與實踐, 2010.

Chan G.C.F., The scientific approach of studying the effects of herbal extracts in medicine., National Hematology Society Meeting, Manila, Philippines, Sept 13, 2009. (Asia Brewery Medical Scholar Lecture).. 2009.

Chan G.C.F., Shing M.M.K., Yuen H.L., Lee A.C.W., Li C.K., Luk C.W. and Li C.K., Treatment Outcome of Metastatic Neuroblastoma with Antiganglioside 2 Monoclonal Antibody (3F8): the Hong Kong Experience. , Society of International Pediatric Oncology (SIOP) Annual Meeting, San Paolo, Brazil, Oct 10-14, 2009. (Awarded Presentation Session) . 2009.

Chan G.C.F., Treatment of Relapsed or Refractory Childhood Solid Tumors, Where are We Now?, Education Workshop of Sun Hua Children’s Hospital. Shanghai, China. May 23, . 2010.

Chan G.C.F., Shing M.M.K., Luk C.W., Lee A.C.W., Ling A.S.C., Li C.K. and Ha S.Y., Treatment outcome of metastatic neuroblastoma with antiganglioside 2 monoclonal antibody (3F8): The Hong Kong experience., 41th Congress of the International Society of Paediatric Oncology, Sao Paulo, Brazil, 5 – 9 October 2009. (Award Presentation Session). 2009.

Chan G.C.F., Fung K.L. and Liang R.H.S., Vincristine but not imatinib could suppress mesenchymal niche’s support to acute lymphoid leukemic (ALL) cells., 41th Congress of the International Society of Paediatric Oncology, Sao Paulo, Brazil, 5 – 9 October 2009.. 2009.

Chan G.C.F., 腦腫瘤治療新曙光, In: LKS Faculty of Medicine, HKU, 育醫造才探索醫學世界, 2010.

Chan I.H.Y., Wong K.K.Y., Chan G.C.F. and Tam P.K.H., Surgical outcomes of patients with neuroblastoma in a tertiary centre in Hong Kong: a 12-year experience, Hong Kong Journal of Paediatrics (New Series). 2009, 14(3): 186-193.

Chen J., Chan G.C.F. and Yang M., Human cytomegalovirus inhibited megakaryocytic differentiation, maturation and induced apoptosis in vitro., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Chen J., Chan G.C.F., Ye J., He Z.X., Wang Q.W., Pan S.N., Li X.F., Deng R.X. and Yang M., Human cytomegalovirus inhibited megakaryocytic differentiation, maturation and induced apoptosis in vitro, Blood [Abstract in 2009 American Society of Hematology], 22 November 2009. 114: 2413.

Chen M., Chan S., Yang M., Chan G.C.F. and Cheung Y.F., Travel Award (supervisor of MMed Sc student; Chen Meipian): Iron overload induced apoptosis in HL-1 cardiomyocytes via mitochondria-mediated caspase-3 dependent pathways, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association. Taipei, Taiwan, PR China 2010. . 2010.

Chen W., Wong V.C.N., Yang M. and Chan G.C.F., Calcium Channel blockers can reduce iron-induced apoptosis in neuroal stem cells, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Cheuk D.K.L., Chiang A.K.S., Chan G.C.F. and Ha S.Y., Urate oxidase for the prevention and treatment of tumor lysis syndrome in children with cancer, Cochrane Database Syst Rev. 2010;6:CD006945. 2010, 6: 1-48.

Cheung K.W., Sze D.M.Y., Koo M.W.L. and Chan G.C.F., Artepillin C could suppress allogeneic human CD4T cells proliferation as brazilian green propolis but with different mechanisms., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. (oral presentation) Dec 2-3. 2009.

Cheung Y.F., Hong W., Chan G.C.F., Wong S.J. and Ha S.Y., Left ventricular myocardial deformation and mechanical dyssychrony in chidlren with normal ventricular shortening fraction after anthracyline therapy , The 6th Korea-Japan-China Pediatric Heart Forum, March 26-27, Seoul, Korea. 2010.

Cheung Y.F., Liang X., Chan G.C.F., Wong S.J. and Ha S.Y., Myocardial deformation in patients with beta-thalassemia major: a speckle tracking echocardiographic study , Echocardiography. 2010, 27: 253-259.

Deng R., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui Buxue Tang (DBT) and its major components on hematopoiesis., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Deng R.X., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui and its component Ferulic Acid on haematopoiesis and platelet production, Blood [Abstract in 2009 American Society of Hematology], 20 November 2009. 114.

Fung K.L., Liang R.H.S. and Chan G.C.F., Vincristine But Not Imatinib Could Suppress Mesenchymal Niche’s Support to Lymphoid Leukemic Cells, Leukemia Lymphoma. 2010, 51(3): 515-522.

Ha S.Y., Mok S.P., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*. , Hemoglobin. 2009, 33(5): 323-331.

Ha S.Y., Mok S.P., Chu W.C.W., Rasalkar D.D., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*., Hemoglobin (Proceedings of the 17th International Conference on Chelation (ICOC), Shenzhen, PR China 23-27 November 2007).. 2009, 33(5): 323-331.

Lam C.L.K., Chan G.C.F., Lam T.H., Lee P.P.W., Leung A.Y.M., Leung G.K.K. and Tsao G.S.W., 育醫造才: 探索醫學世界, 2010.

Lee D.C.W., Yang L.H., Chik S.C.C., Li J., Rong J., Chan G.C.F. and Lau A.S.Y., Immunomodualtory effect of Panax ginseng on human promonocytic U937 cells, Journal of Translational Medicine. 2009, 7: 34-40.

Ma M. and Chan G.C.F., Human mesenchymal stromal cells derived chemokines with potential involvement in neuroblastoma metastasis., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Ngan E.S.W., Lau C.S.T., Wo Y.H., Chan W.K., Chan G.C.F., Wang Y., Kaplan D. and Tam P.K.H., Endocrine-gland vascular endothelial growth factor (EG-VEGF) in neuroblastoma tumor initiating cells, Advances in Neuroblastoma Research 2010, Stockham, Sweden, 21-24 June 2010.

Nie Y., Lau W.C.S., Lie A.K.W., Chan G.C.F. and Mok T.M.Y., Defective phenotype of mesenchymal stem cells in patients with systemic lupus erythematosus, Lupus. 2010, 19: 850-9.

Nie Y., Mok T.M.Y., Chan G.C.F., Chan W.K., Jin O., Kavikondala S., Lie A.K.W. and Lau W.C.S., Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus, Arthritis Res Ther . 2010, 12: R91.

Nie Y.J., Mok M.Y., Chan G.C.F., Chan A., Jin O., Kavikondala S. and Lau C.S., Deficiencies of bone marrow-derived dendritic cells in systemic lupus erythematosus., Artritis Research and Theraphy 2010;18;12(3):R91. 2009.

Qiu D., Chan G.C.F., Chan Q., Ha S.Y. and Khong P.L., Susceptibility weighted imaging (SWI) for the assessment of iron loading in the brain of beta-thalassemia major patients., 1st meeting of the Asia-Pacific Iron Academy, Chiang Mai, 23-26 Nov 2009.

Sze D.M.Y. and Chan G.C.F., Supplement for immune enhancement in hematologic malignancies, Haematology 2009 (in press). 2009.

Sze D.M.Y. and Chan G.C.F., Supplements for immune enhancement in hematologic malignancies., American Society of Hematology 2009; 303-9.. 2009, 303-309.

Tso H.W., Law H.K.W., Tu W., Chan G.C.F. and Lau Y.L., Phagocytosis of apoptotic cells modulates mesenchymal stem cells osteogenic differentiation to enhance IL-17 and RANKL expression on CD4+ T cells, Stem Cells. 2010, 28: 939-954.

Wong H.L., Wong M.Y., Chan G.C.F., Yang Z. and Chan B.P., Functionally selecting human mesenchymal stem cell subpopulations with better migratory activities using a collagen barrier. , 7th Annual Meeting of International Society for Stem Cell Research, Jul 8-11, 2009. Barcelona, Spain.. 2009, 1265.

Ye J., Chan G.C.F. and Yang M., Effect of recombinant PDGF-BB on thrombopoiesis in a mouse model., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Yu J., Chan G.C.F. and Yang M., Platelet-derived growth factor enhances platelet recovery in a radiation-induced thrombocytopenic mouse model and reduces apoptosis in megakaryocytes via its receptors and PI3- k/Akt pathway, Haematologica. 2010, 95: 1745-1753.

Zhou L., Hou J., Chan G.C.F. and Sze D.M.Y., Arsenic trioxide for non-acute promyelocytic leukemia hematological malignancies: a new frontier. , Current Cancer Drug Target 2009 (in press). 2009.

Researcher : Chan KW

List of Research Outputs

Lee P.P.W., Chen T.X., Jiang L.P., Chan K.W., Yang W., Lee B.W., Chiang W.C., Chen X.Y., Fok S.F.S., Lee T.L., Ho M.H.K., Yang X.Q. and Lau Y.L., Clinical Characteristics and Genotype-phenotype Correlation in 62 patients with X-linked Agammaglobulinemia, Journal of Clinical Immunology. 2010, 30: 121-131.

Lee P.P.W., Lee T.L., Ho M.H.K., Zeng H.S., Chen X.Y., Chan K.W., Tu W. and Lau Y.L., Invasive Penicillium marneffel Infection in Children without Acquired Immunodeficiency Syndrome (AIDS) - An Indicator Disease for Primary Immunodeficiency?, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W., Chan K.W., Chen T.X., Jiang L.P., Wang X.C., Zeng H.S., Chen X.Y., Lee B.W., Shek L., Liew W.K., Lee C.W., Yu H.H., Latiff Z.A., Ho M.H.K., Lee T.L. and Lau Y.L., Molecular diagnosis of severe combined immunodeficiency - Identification of IL2RG, JAK3, IL7R, DCLRE1C and RAG2 mutations in a cohort of Chinese and Southeast Asian children, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W., Lau Y.L., Ho M.H.K., Lee T.L. and Chan K.W., Primary Immunodeficiency Referral Network in Asia: Database Review 2001 – 2009, Young Investigator Award, 6th Congress of Asian Society for Pediatric Research . 2010.

Lee P.P.W., Chan K.W., Wong W.H.S., Ho M.H.K., Lee T.L. and Lau Y.L., Primary Immunodeficiency Referral Network in Asia: Database Review 2001-2009, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Researcher : Chan KY

List of Research Outputs

Mak C.M., Lam C.W., Siu T.S., Chan K.Y., Siu C.W.K., Yeung W.L., Hui J., Wong V.C.N., Low L.C.K., Ko C.H., Tam S. and Chan Y.W., Biochemical and molecular characterization of tyrosine hydroxylase deficiency in Hong Kong Chinese, Molecular Genetics and Metabolism. 2010, 99(4): 431-433.

Researcher : Chan LLY

List of Research Outputs

Chan L.L.Y., Cheung B.K.W., Li C.B. and Lau A.S.Y., A role for STAT3 and cathepsin S in IL-10 down-regulation of IFN-γ-induced MHC class II molecule on primary human blood macrophages., Journal of Leukocyte Biology. 2010, 88: 1-9.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., A role for STAT3 in IL-10 downregulation of IFN-g-induced MHC class II molecule expression on primary human blood macrophages., Third Annual Scientific Meeting, The Hong Kong Society for Paediatric Immunology and Infectious Diseases Saturday, March 20, . 2010.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., A role for STAT3 in IL-10 downregulation of IFN-γ-induced MHC class II molecule expression on primary human blood macrophages., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. December 2-3. 2009.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., A role for STAT3 in IL-10 downregulation of IFN-γ-induced MHC class II molecule expression on primary human blood macrophages., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-0100]. 2009.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., Mechanisms underlying mycobacterial and HIV dysregulations of the immune system: a role for IL-10 and Stat3 dependent pathways in the suppression of interferon-g reglated cellular responses., Invited plenary session presentation for Asia Pacific Inflammation Research 2010.. 2010.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., Runner-up oral presentation Award, Third Annual Scientific Meeting, The Hong Kong Society for Paediatric Immunology and Infectious Diseases Saturday, 20th March 2010. 2010.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., Seymour and Vivian Milstein Travel Awards, Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009. 2009.

Researcher : Chan PL

List of Research Outputs

Mao H., Tu W., Qin G., Law H.K., Sia S.F., Chan P.L., Liu Y., Lam K.T., Zheng J., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, J Virol. 2009, 83(18): 9215-22.

Mao H., Tu W., Qin G., Lau H.K.W., Chan P.L., Liu Y., Lam K.T., Zhang Y., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, Journal of Virology. 2009, 83: 9215-9222.

Mao H., Tu W., Liu Y., Qin G., Zheng J., Chan P.L., Lam K.T., Peiris J.S.M. and Lau Y.L., Inhibition of human natural killer cell activity by influenza virions and hemagglutinin, J Virol. 2010, 84(9): 4148-57.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded Human Gammadelta T Cells Display Potent Cytotoxicities Towards Human and Avian Influenza Virus-infected Monocyte-derived Macrophages, clinical immunology. 2009, 131: s91-s92.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Lam K.T., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses, J Infect Dis. 2009, 200(6): 858-65.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., lewis D.B., Lau Y.L. and Tu W., Efficient Induction and Expansion of Human Alloantigen-Specific CD8 Regulatory T Cells from Naive Precursors by CD40-Activated B Cells. , Journal of Immunology. U.S.A., 2009, 2009 Aug 14.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., Lewis D.B., Lau Y.L. and Tu W., Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells, J Immunol. 2009, 183(6): 3742-50.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H.W., Lewis D.B., Lau Y.L. and Tu W., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, Clinical Immunology. 2009, 131: S163-S163.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lewis D.B. and Lau Y.L., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, clinical immunology. 2009.

Researcher : Chan PL

List of Research Outputs

Researcher : Chan S

List of Research Outputs

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (Deferoxamine, deferiprone and deferasirox) on the growth of klebsiella pneumoniae and aeromonas hydrophila isolated from transfusion-dependent thalassaemia patients., Hemoglobin (Proceedings of the 17th International Conference on Chelation (ICOC), Shenzhen, PR China 23-27 November 2007). 2009, 33(5): 352-360.

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (Desferal, Deferiprone & Deferaairox) on the growth of klebsiella and aeromonas isolated from transfusion dependent thalassaemia patients., Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association Ltd. 28 November. 2009.

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (desferal, deferiprone & deferasirox) on the growth of Klebsiella and Aeromonas isolated from transfusion dependent thalassemia patients., Hemoglobin. 2009, 33(5): 352-360.

Chen M., Chan S., Yang M., Chan G.C.F. and Cheung Y.F., Travel Award (supervisor of MMed Sc student; Chen Meipian): Iron overload induced apoptosis in HL-1 cardiomyocytes via mitochondria-mediated caspase-3 dependent pathways, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association. Taipei, Taiwan, PR China 2010. . 2010.

Researcher : Chan SHS

List of Research Outputs

Chan S.H.S., Mak W. and Wong V.C.N., A girl with atypical chronic inflammatory demyelinating polyneuropathy, 11^th International Child Neurology Congress, Cairo, Egypt, 2-7 May 2010. The International Journal of Child Neuropsychiatry (poster presentaion). 2010, 90.

Chan S.H.S., Mak W. and Wong V.C.N., A girl with atypical chronic inflammatory demyelinating polyneuropathy, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Chan S.H.S., Fung C.W., Yung A.W.Y., Lee S.L., Wong V.C.N., Dale R.C. and Vincent A.C., Anti-NMDA-R encephalitis - an encephalitis lerthargica-like illness, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Chan S.H.S., Wong V.C.N., Fung C.W., Dale R.C., Vincent A., Yung A.W.Y. and Lee S.L., Anti-NMDAR encephalitis - An encephalitis lethargica like illness, 11^th International Child Neurology Congress, Cairo, Egypt, 2-7 May 2010. The International Journal of Child Neuropsychiatry (poster presentaion). 2010, 184.

Researcher : Chan SY

Project Title:	Characterisation of NAP79 transgenic mice
Investigator(s):	Chan SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2006
Completion Date:	10/2009

Abstract:

Objective: To determine the function of NAP79 in cardiomyocyte proliferation by analysing transgenic mice with prolonged expression of NAP79. Key issues and problems being addressed: Our group has identified a novel 79 kDa nucleosome assembly protein, NAP79, from human heart cDNAs [1]. Nucleosome assembly proteins (NAPs) deposit histones onto DNA, which is important in nucleosome remodelling during DNA replication and gene transcription, and in controlling mitotic events. In mice, we found that Nap79 transcripts are mainly expressed in the neonatal heart and brain. We have raised antibodies against NAP79 and found that the cardiac expression of NAP79 decreases dramatically during the neonatal period. This is of great interest since cardiomyocytes permanently withdraw from the cell cycle within the first 2 weeks in mice and within 3-6 months in humans, and so the number of proliferating cardiomyocytes gradually decline during these periods. Is NAP79 expressed only in proliferating cardiomyocytes and switched off once the cells exit the cell cycle? Our preliminary experiments to knock down Nap79 expression by siRNA in the myoblast cell line C2C12 have shown an effect on the rate of cell proliferation and the cells can no longer undergo terminal differentiation. Based on its domain structure, expression pattern and the effect of siRNA, we hypothesize that NAP79 plays a role in regulating the proliferation/ terminal differentiation of cardiomyocytes. There are two possible mechanisms of how NAP79 may fuction in controlling cardiomyocyte proliferation: 1. Expression of NAP79 is required to keep cardiomyocyte in the cell cycle. 2. The peak cardiac expression of NAP79 during the neonatal period is a signal for cell cycle exit/ terminal differentiation. If the first situation is correct, then prolonging the expression of NAP79 may delay cell cycle exit of cardiomyocytes. By contrast, increasing the level of NAP79 may cause earlier exit of cardiomyocytes from the cell cycle if the second mechanism is correct. To test our hypothesis, we have generated transgenic mice with a HA-tagged human NAP79 cDNA driven by cardiomyocyte specific promoters. This can both increase and prolong the cardiac expression of NAP79. We have obtained two transgenic lines which express the transgene as measured by RT-PCR in the neonatal and adult heart samples. Given the complex nature of cell cycle control in vivo, it is not surprising that our transgenic mice do not show an overt change in heart to body weight ratio. As in other reports on transgenic mice of cell cycle regulators (eg. cyclin D1, D2 and A2), expression of positive cell cycle regulators or even mitosis may be increased in the postnatal myocardium. This proposal aims at analysing cardiomyocyte proliferation in the neonatal period of our transgenic animals. We shall perform immunostaining and analyse the percentage of proliferating cardiomyocytes at around day 2 and day 10 after birth. Reference: 1. Sun G et al. Isolation of differentially expressed genes in human heart tissues (2002) Biochimica et Biophysica Acta - Mechanisms of disease 1588, 241 -246.

Project Title:	Validation of protein interacting partners of NAP79 and the biological significance
Investigator(s):	Chan SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	01/2008
Completion Date:	12/2009

Abstract:

Objective: To understand the function of NAP79 through identification of its protein interacting partners Key issues and problems being addressed: Our group has identified a novel 79 kDa nucleosome assembly protein, NAP79, from human heart cDNAs. Nucleosome assembly proteins (NAPs) deposit histones onto DNA, which is important in nucleosome remodelling during DNA replication and gene transcription. From northern analysis, nap79 is specifically expressed in the mouse brain, heart and gonads. We have successfully raised specific antibodies against NAP79. With this reagent we found that the nuclear expression of NAP79 in cardiomyocytes decreases dramatically during the neonatal period when cardiomyocytes stop proliferation. Based on its domain structure and expression pattern, we hypothesize that NAP79 plays a role in regulating the proliferation and/or terminal differentiation of cardiomyocytes. In support of this hypothesis, knockdown of NAP79 in C2C12 myoblast cell line perturbed its differentiation into myotubes. A better understanding on how NAP79 functions in cardiomyocyte proliferation and differentiation may be achieved with knowledge of the interacting proteins. For example, the interaction between B-type cyclins and NAP1 or SET, two other members of the NAP family, readily gives insights into how NAP1 and SET regultate mitotic activity. The most widely used approach for this purpose is yeast two-hybrid screening. Our group has performed yeast two-hybrid screening for identifying potential protein interacting partners of NAP79. Several nuclear proteins have came up in the pilot screen and we are in the process of sequencing the remaining positive clones. A second independent test, such as co-immunoprecipitation, pull down assay or FRET assay, is required for validation of the positive clones as true protein interacting partners of NAP79. For selecting the candidates for validation, priority will be given to nuclear proteins. So far we have selected four candidates for validation, which will be followed by functional studies based on the functions already annotated to these interacting proteins. More candidates are expected as we are completing the yeast two-hybrid screen. We are especially interested in one of the candidates, namely four-and-a-half-LIM only protein FHL2. FHL2 is a muscle-specific repressor of LEF/TCF target genes and promotes myogenic differentiation by interacting with ß-catenin. The gene encoding FHL2 has been disrupted by homologous recombination, and knockout mice devoid of FHL2 were found to undergo normal cardiovascular development. In the absence of FHL2, however, cardiac hypertrophy resulting from chronic infusion of isoproterenol is exaggerated (1). Furthermore, FHL2 interacts with a variety of transcription factor known to be involved in tumor development (2). Lastly, FHL2 is implicated in splicing as it interacts with the splicing factor NP220 (3). Interestingly, we have also identified a small protein involved in splicing as a candidate protein interacting partner of NAP79. 1. Kong Y et al. Cardiac-specific LIM protein FHL2 modifies the hypertrophic response to beta-adrenergic stimulation. Circulation (2001) 103: 2731-2738. 2. Kleiber K et al. The biological relevance of FHL2 in tumor cells and its role as a putative cancer target. Anticancer Research (2007) 27:55-61. 3. Ng EK et al. Interaction of the heart-specific LIM domain protein, FHL2, with DNA-binding nuclear protein, hNP220. Journal of Cellular Biochemistry (2002) 84: 556-566.

Project Title:	Phenotype analysis of Tspyl2/Nap79 knockout mice
Investigator(s):	Chan SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2009

Abstract:

The reversible assembly of DNA and histones into chromatin is important in cell proliferation and regulation of gene expression. Nucleosome assembly proteins (NAPs) are involved in this process but so far reports are mainly on in vitro biochemical studies. These studies show that some NAPs can interact with cell cycle proteins. The physiological functions of NAPs are poorly understood. We previously identified a novel nucleosome assembly protein NAP79, recently coined TSPYL2 in the NCBI database, which is highly expressed in the human brain and heart. To dissect the physiological functions of Tspyl2, we have generated mice deficient in Tspyl2. Interestingly, these Tspyl2 ‘knockout’ mice are viable and fertile, although with subtle defects in brain function as revealed by electro-physiological studies. The viable and fertile mutant mice have provided us a unique opportunity to dissect the in vivo functions of Tspyl2. Based on the literature reporters on Tspyl2 and on other NAPs, I hypothesize that Tspyl2 has a dual role in cell cycle control upon DNA damage and in transcriptional regulation. The proposal for external funding will focus on one of these two areas depending on the pilot results obtained with the present seed grant proposal. Key issue: Is Tspyl2 involved in preventing unwanted cell proliferation when cells are under stress, such as DNA damage? Objective 1: In this proposal, we aim to determine the role of Tspyl2 in cell cycle regulation in response to DNA damage. Primary fibroblasts are derived from the knockout and wildtype embryos. We shall induce DNA damage in these culture cells by ionization radiation to determine the importance of Tspyl2 in cell cycle checkpoint responses. Key issue: Is Tspyl2 involved in transcriptional regulation in neurons? Objective 2: To identify the potential transcriptional targets of Tspyl2 by comparing the expression of selected genes in brain samples collected from wildtype and knockout mice. The selected genes include those known to be involved in learning and memory, as our mutant mice show a defect in long term potential in electrophysiological study. Long term potentiation is related to learning and memory.

Project Title:	The effect of Tspyl2, a Novel Nucleosome Assembly Protein, on gene expression profile in the hippocampus
Investigator(s):	Chan SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	12/2009

Abstract:

Background: The reversible assembly of DNA and histones into chromatin is important in regulation of gene expression. Nucleosome assembly proteins (NAPs) are involved in this process. So far reports on NAPs are mainly in vitro biochemical studies, such as their preference for binding various histone proteins, and the identification of other interacting partners. Although their ability to assemble DNA and histones into chromatin has also been shown, the physiological functions of NAPs remain poorly understood. We previously identified from heart biopsies a novel nucleosome assembly protein NAP79 [1], recently coined TSPY-like 2 (Tspyl2) due to the homology of its NAP domain to that in testis-specific protein, Y-encoded (TSPY). Tspyl2 is highly expressed in the human brain and heart. To dissect the physiological functions of Tspyl2, we have generated mice deficient in Tspyl2. Interestingly, these Tspyl2 ‘knockout’ mice are viable and fertile, although with defects in brain function as revealed by electro-physiological and behavioural studies. The viable and fertile mutant mice have provided us a unique opportunity to dissect the in vivo functions of Tspyl2. Objective: To identify genes which are deregulated in the hippocampus of Tspyl2 knockout mice NAPs are believed to regulate the expression of multiple target genes through its effect on the compactness of chromatin. I hypothesize that Tspyl2 plays important roles in brain functions through regulating transcription of multiple genes in neurons. Also these target genes should be specific. This is supported by the finding that mice with a mutation in genes involved in epigenetic regulation of gene transcription have consistent phenotype [2, 3] This suggests that the chromatin remodelling is targeted at specific genes. This is substantiated by microarray analysis [3, 4]. To establish a role of Tspyl2 in regulating gene expression, we first compare the gene expression in corresponding brain regions in wildtype mice and their knockout littermates by RT-PCR and western blotting. Given the normal neuroanatomy of our mutant mice, as revealed by the commonly used Nissl stain, we are in a good position to compare gene expression with the wildtype. Based on our positive findings on the electro-physiological and behavioural studies, we collected RNA and protein samples from the hippocampus and cortex and tested a few genes which are involved in learning and memory. As a circumstantial evidence that Tspyl2 regulates neuronal gene transcription, we consistently demonstrate a reduction, although not statistically significant, in the expression of the components for excitatory glutamergic transmission, governed by the NMDA receptors (Nr). For example, Nr2A is the major isoform in the adult brain and its expression is reduced in the mutant (Fig. 1, attached). Key issue: What are the deregulated genes in Tspyl2 knockout mice which could lead to the abnormal behavioural phenotype? The abnormal phenotype in our mutant mice includes impaired long term potentiation, which is often implicated in the strengthening of synapses for learning and memory; impairment of prepulse inhibition of startle, which is found in several behavioural disorders in humans including attention deficit hyperactive disorder and schizophrenia. The deregulated expression of multiple genes is likely to be the cause of the behavioural defects both in our mouse mutant and in humans. The deregulated expression can either be a direct effect of Tspyl2 on gene transcription; or a secondary effect due to neuron dysfunction. As a first step to identify the target genes of Tspyl2 in neurons, I shall address its potential gene targets by gene expression profiling in brain RNA samples with and without Tspyl2 using microarray technology in the current proposal. The results will be verified by reverse transcription-quantitative PCR. This will open up follow up projects on sorting out the direct gene targets of Tspyl2 versus those which change their expression levels due to secondary effects. The ultimate goal is to dissect how Tspyl2 regulates neuron function. References: 1. Sun, G., et al., Isolation of differentially expressed genes in human heart tissues. Biochim Biophys Acta, 2002. 1588(3): p. 241-6. 2. Alarcon, J.M., et al., Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron, 2004. 42(6): p. 947-59. 3. Ben-Shachar, S., et al., Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus. Hum Mol Genet, 2009. 18(13): p. 2431-42. 4. Jordan, C., et al., Cerebellar gene expression profiles of mouse models for Rett syndrome reveal novel MeCP2 targets. BMC Med Genet, 2007. 8: p. 36.

Project Title:	43rd Annual Meeting for the Japanese Society of Developmental Biologists The Nucleosome Assembly Protein Tspyl2 Represses Transcription
Investigator(s):	Chan SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	06/2010
Completion Date:	06/2010

Abstract:

N/A

List of Research Outputs

Chan S.Y., Chairman, Frontiers in Biomedical Research, HKU 2009, 4 December 2009. 2009.

Chan S.Y., Chairman, Genetic Disorders in Reproduction and Fetal Development - From Science to Clinical Practice, HKU 2009, 25 Octobe 2009. 2009.

Chan S.Y., Facilitator, Workshop on Animal Research Ethics, HKU 2009, 12 January 2010. 2010.

Chan S.Y., Making Transgenic and Knockout Mice, International Brain Research Organization. 2010.

Chan S.Y., Moderator, 14^th Research Postgraduate Symposium, HKU, 2-3 December 2009. 2009.

Chan S.Y., Wong H.T. and Tsang K.H., The nucleosome assembly protein TSPYL2 represses transcription, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010.

Lee P.P.W., Chung B.H.Y., Chan S.Y. and Lau Y.L., Teaching and Learning Medical Genetics - An Interactive Genetics Workshop for Paediatric Clerkship Students, First Runner-up,, Best Poster Presentation: 7^th Asia Pacific Medical Education Conference (APMEC): Excellence in Medical Education - Quality in Healthcare (Trends, Issues, Priorities, Strategies), Medical Education Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 4-8 Februray 2010.

Lee P.P.W., Chung B.H.Y., Chan S.Y. and Lau Y.L., Teaching and Learning Medical Genetics - An Interactive Workshop for Undergraduate Medical Students, 7th Asia Pacific Medical Education Conference, Runner up Poster presenter. 2010.

Tao K.P. and Chan S.Y., Functional analysis of Tspyl2 in cell proliferation, The British Association for Cancer Research/The European Association for Cancer Research, Chromatin and Cancer Symposium, Cambrigde, UK, 6-8 Julyy 2009.

Tao K.P., Lai S.K., Chan Y.S., Sham M.H. and Chan S.Y., Tspyl2 is involved in Cellular Stress Response and Brain Function, 14^th Research Postgraduate Symposium, HKU, 2-3 December 2009.

Tsang K.H., Lai S.K., Chan Y.S. and Chan S.Y., Testis-specific Protein Y-linked-Like 2 (Tspyl2) Regulates Hippocampal Long-term Potentiation via NMDA Receptors Expression and p38MAPK Activity, 14^th Research Postgraduate Symposium, HKU, 2-3 December 2009.

Tsang K.H., Tao K.P., Lai S.K., Chan Y.S. and Chan S.Y., Tspy 12 regulates hippocampal long-term potentiation via NMDA receptor subunits Nr2a and Nr2b expression, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010. 2010.

Tsang K.H., Tao K.P., Lai S.K., Chan Y.S. and Chan S.Y., Tspy12 regulates hippocampal long-term potentiation via NMDA receptor subunits Nr2a and Nr2b expression, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010.

Wong H.T., Chiu R.P.H. and Chan S.Y., A role of TSPYL2, a novel nucleosome assembly protein, in transcriptional regulation, The British Association for Cancer Research/The European Association for Cancer Research, Chromatin and Cancer Symposium, Cambrigde, UK, 6-8 Julyy 2009.

Researcher : Chan WK

List of Research Outputs

Ngan E.S.W., Lau C.S.T., Wo Y.H., Chan W.K., Chan G.C.F., Wang Y., Kaplan D. and Tam P.K.H., Endocrine-gland vascular endothelial growth factor (EG-VEGF) in neuroblastoma tumor initiating cells, Advances in Neuroblastoma Research 2010, Stockham, Sweden, 21-24 June 2010.

Researcher : Chau AKT

List of Research Outputs

Ko L.Y., Chau A.K.T., Yung T.C., Cheung Y.F. and Lun K.S., Retrospective Review on Anomalous Left Coronary Artery from Pulmonary Artery , Hong Kong Journal of Paediatrics . 2010, 15: 12-18.

Li X., Cheng L.C., Cheung Y.F., Lun K.S., Chau A.K.T. and Chiu S.W., Management of symptomatic congenital tracheal stenosis in neonates and infants by slide tracheoplasty: a 7-year single institution experience, European Journal of Cardio-thoracic Surgery. 2010, Epub ahead of print.

Lun K.S., Fan K., Yung T.C., Wong K.T., Cheung Y.F., Chau A.K.T. and Cheng L.C., Experience of pediatric heart transplantation in Hong Kong, International Congress of Cardiology, Hong Kong, 26-28 February 2010.

Lun K.S., Fan K., Wong C.F., Yung T.C., Chow P.C., Wong K.T., Cheung Y.F., Chow W.H., Chau A.K.T., Chiu S.W. and Cheng L.C., Outcome of thoracic organ transplantation for adults with congenital heart disease, 18^th Annual Scientific Congress, Hong Kong College of Cardiology, Hong Kong, 14-16 May 2010.

Tsang F.H.F., Li X., Cheung Y.F., Chau A.K.T. and Cheng L.C., Pulmonary valve replacement after surgical repair of Tetralogy of Fallot, Hong Kong Medical Journal . 2010, 16: 26-30.

Researcher : Chen J

List of Research Outputs

Chen J., Chan G.C.F. and Yang M., Human cytomegalovirus inhibited megakaryocytic differentiation, maturation and induced apoptosis in vitro., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Chen J., Chan G.C.F., Ye J., He Z.X., Wang Q.W., Pan S.N., Li X.F., Deng R.X. and Yang M., Human cytomegalovirus inhibited megakaryocytic differentiation, maturation and induced apoptosis in vitro, Blood [Abstract in 2009 American Society of Hematology], 22 November 2009. 114: 2413.

Deng R., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui Buxue Tang (DBT) and its major components on hematopoiesis., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Deng R.X., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui and its component Ferulic Acid on haematopoiesis and platelet production, Blood [Abstract in 2009 American Society of Hematology], 20 November 2009. 114.

Researcher : Chen M

List of Research Outputs

Chen M., Chan S., Yang M., Chan G.C.F. and Cheung Y.F., Travel Award (supervisor of MMed Sc student; Chen Meipian): Iron overload induced apoptosis in HL-1 cardiomyocytes via mitochondria-mediated caspase-3 dependent pathways, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association. Taipei, Taiwan, PR China 2010. . 2010.

Researcher : Chen W

List of Research Outputs

Chen W., Wong V.C.N., Yang M. and Chan G.C.F., Calcium Channel blockers can reduce iron-induced apoptosis in neuroal stem cells, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Chen W., Wong V.C.N. and Liu W.L., Double Blind Randomized Control Trial of Acupuncture for Autistic Spectrum Disorder, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Chen W., Liu W.L. and Wong V.C.N., Electroacupuncture for children with autism spectrum disorder: pilot study of 2 cases. , Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November, 2009.. 2009.

Researcher : Chen W

List of Research Outputs

Researcher : Cheng M

List of Research Outputs

Li C.B., Cheng M., Yim H.C.H., Lee D.C.W. and Lau A.S.Y., Mechanisms underlying HIV-1 suppression of IFN-γ signaling pathways: A role for transactivator Tat in the induction of SOCS-2 in primary human blood monocytes., Tri-Society Annual Conference, Lisbon, Portugal, October 18-21. 2009.

Researcher : Cheuk DKL

List of Research Outputs

Cheuk D.K.L., Chiang A.K.S., Chan G.C.F. and Ha S.Y., Urate oxidase for the prevention and treatment of tumor lysis syndrome in children with cancer, Cochrane Database Syst Rev. 2010;6:CD006945. 2010, 6: 1-48.

Ha S.Y., Mok S.P., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*. , Hemoglobin. 2009, 33(5): 323-331.

Ha S.Y., Mok S.P., Chu W.C.W., Rasalkar D.D., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*., Hemoglobin (Proceedings of the 17th International Conference on Chelation (ICOC), Shenzhen, PR China 23-27 November 2007).. 2009, 33(5): 323-331.

Mak K.K., Ho D.S.Y., Thomas G.N., Lo W.S., Cheuk D.K.L., Lai Y.K. and Lam T.H., Smoking and sleep disorders in Chinese adolescents, Sleep Medicine. 2010, 11(3): 268-273.

Researcher : Cheung BKW

List of Research Outputs

Chan L.L.Y., Cheung B.K.W., Li C.B. and Lau A.S.Y., A role for STAT3 and cathepsin S in IL-10 down-regulation of IFN-γ-induced MHC class II molecule on primary human blood macrophages., Journal of Leukocyte Biology. 2010, 88: 1-9.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., Mechanisms underlying mycobacterial and HIV dysregulations of the immune system: a role for IL-10 and Stat3 dependent pathways in the suppression of interferon-g reglated cellular responses., Invited plenary session presentation for Asia Pacific Inflammation Research 2010.. 2010.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., Runner-up oral presentation Award, Third Annual Scientific Meeting, The Hong Kong Society for Paediatric Immunology and Infectious Diseases Saturday, 20th March 2010. 2010.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., Seymour and Vivian Milstein Travel Awards, Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009. 2009.

Or C.T., Yang L.H., Cheung B.K.W. and Lau A.S.Y., Mechanisms of Ligusticum chuanxiong (LCX) extracts in the suppression of proinflammatory cytokine expression in blood macrophages, 9^th World Congress on Inflammation 2009, Tokyo, Japan, 8 July. 2009.

Researcher : Cheung EWY

List of Research Outputs

Cheung E.W.Y., Liang X., Lam W.W.M. and Cheung Y.F., Impact of right ventricular dilation on left ventricular myocardial deformation in patients after surgical repair of Tetralogy of Fallot, American Journal of Cardiology. 2009, 104: 1264-1270.

Cheung E.W.Y., Wong W.H.S. and Cheung Y.F., Systematic review and meta-analysis of pulmonary valve replacement in children and adults after surgical repair of tetralogy of Fallot, The 6th Korea-Japan-China Pediatric Heart Forum, March 26-27, 2010, Seoul, Korea . 2010.

Cheung Y.F., Cheung E.W.Y. and Wong W.H.S., Systematic review and meta-analysis of pulmonary valve replacement in children and adults after surgical repair of tetralogy of Fallot, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association. Taipei, Taiwan, China 2010. . 2010.

Liang X., Lam W.W.M., Cheung E.W.Y., Wu A.K.P., Wong S.J. and Cheung Y.F., Restrictive Right Ventricular Physiology and Right Ventricular Fibrosis as Assessed by Cardiac Magnetic Resonance and Exercise Capacity After Biventricular Repair of Pulmonary Atresia and Intact Ventricular Septum , Clinical Cardiology . 2010, 33: 104-110.

Researcher : Cheung KW

List of Research Outputs

Cheung K.W., Sze D.M.Y., Koo M.W.L. and Chan G.C.F., Artepillin C could suppress allogeneic human CD4T cells proliferation as brazilian green propolis but with different mechanisms., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. (oral presentation) Dec 2-3. 2009.

Researcher : Cheung PT

Project Title:	The Endocrine Society 83rd Annual Meeting Mutations of the CYP11B2 Gene in a Patient with Corticosterone Methyl Oxidase Type II Deficiency
Investigator(s):	Cheung PT
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	06/2001

Abstract:

N/A

Project Title:	International Perinatal Collegium 2005 Meeting New Approaches in Old Models - Identification of Novel Molecular Alterations in Neonatal Mouse Hypoxic-Ischaemic Brain Damage
Investigator(s):	Cheung PT
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	07/2005

Abstract:

N/A

Project Title:	4th Asian Epigenomics Meeting Methyl mercury induced epigenetic dysregulation of BDNF gene in NG108 cells in vitro – a possible mechanism of environment-epigenome interactions underlying neuropsychiatric and neurodevelopmental disorders.
Investigator(s):	Cheung PT
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	08/2009

Abstract:

N/A

List of Research Outputs

Bhatia I., Tsim K.W. and Cheung P.T., Methyl mercury induced epigenetic dysregulation of BDNF gene in NG108 cells in vitro – a possible mechanism of environment-epigenome interactions underlying neuropsychiatric and neurodevelopmental disorders., 4th Asian Epigenomics Meeting. Singapore Augst 24th -25th, 2009.. 2009.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Siu S., Mak C.M., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitter assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD)(Diamond Prize). 2010.

Fung C.W., Siu S., Blau N., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November, 2009.. 2009.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Blau N., Siu S., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S., Siu S. and Wong V.C.N., Spectrum of mitochondrial diseases in a tertiary referral centre in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Huen K.F., Low L.C.K., Cheung P.T., Wong G.W.K., But B.W.M., Kwan E.Y.W., Lam Y.Y., Lee C.Y., Wong L.M., Ng K.L., Cheng A.W.F., Tong C.T. and Wong W.H.S., An Update on the Epidemiology of Childhood Diabetes in Hong Kong , Hong Kong Journal of Paediatrics . 2009, 14: 252-259.

Poon G.W.K., Kwok A.M.K., Cheung P.T., Yung T.C., Ng Y.K., Tsoi N.S., Wong K.Y. and Low L.C.K., Variable Response to Enzyme Replacement Therapy in Two Chinese Children with Infantile-onset Pompe Disease in Hong Kong , Hong Kong Journal of Paediatrics. 2009, 14: 243-251.

Wang S., Wu E.X., Cai K., Lau H.F., Cheung P.T. and Khong P.L., Mild hypoxic-ischemic injury in the neonatal rat brain: longitudinal valuation of white matter using diffusion tensor MR imaging, American Journal of Neuroradiology. 2009, 30: 1907-1913.

Wu E.X., Chan C.W., Khong P.L., Lau H.F. and Cheung P.T., Late measures of microstructural alterations in severe neonatal hypoxic-ischemic encephalopathy by MR diffusion tensor imaging, International Journal Developmental Neuroscience. 2009, 27: 607-615.

Researcher : Cheung PY

List of Research Outputs

Ting J.Y. and Cheung P.Y., [Letters to the Editor] Cerebral blood flow velocities in extremely low birth weight infants, The Journal of Pediatrics. 2009, 155(6): 944.

Researcher : Cheung YF

Project Title:	CSX/NKX2.5 mutations in patients with pulmonary atresia and intact ventricular septum
Investigator(s):	Cheung YF, Chan SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To determine the possible genetic cause of PAIVS, which is a relatively common cyanotic congenital heart disease in this locality.

Project Title:	Development of a multimedia tool for teaching of paediatric cardiology
Investigator(s):	Cheung YF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Run Run Shaw Research and Teaching Endowment Fund - Teaching Grants
Start Date:	04/2004

Abstract:

To improve the knowledge on congenital heart disease of medical students; thier skills in the evaluation of children with congenital heart disease, and their skills in counseling of parents of paediatric cardiac patients.

Project Title:	Novel real-time 3-dimensional echocardiographic assessment of right and left ventricular function in anthracycline-treated survivors of childhood malignancies
Investigator(s):	Cheung YF, Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	01/2008
Completion Date:	05/2010

Abstract:

Anthracyclines are widely used for the treatment of solid tumours and haematological malignancies in children. While the introduction of anthracyclines has significantly improved the survival rates of childhood cancer, the long-term side effect of cardiotoxicity remains an issue of concern. The pathogenesis of cardiotoxicity is proposed to be related to free radical generation and disruption of myocyte calcium regulation. Damage and myocardial edema within both the left and right ventricles have been identified using magnetic resonance imaging. Importantly, no safe dose of anthracyclines free of cardiotoxicity has been found. Serial monitoring of cardiac function has therefore been advocated for early identification of myocardial damage and timely institution of medical therapy. Furthermore, limited data suggest potential usefulness of exercise echocardiography for unmasking latent cardiac dysfunction in anthracycline-treated survivors of childhood cancer. The most widely used imaging modality for the assessment of cardiac function and diagnosis of cardiotoxicity in these patients is two-dimensional echocardiography given its non-invasive nature. The function of the left ventricle, in particular, has been the focus of attention. The most commonly used echocardiographic parameters to assess left ventricular (LV) function in these patients are LV shortening fraction and LV ejection fraction, the latter calculated from 2-dimensional images based on geometric assumptions. Nonetheless, the major limitations of 2-dimensional echocardiography include the need to make assumptions of the LV geometry and a large inter-observer variability. Assessment of right ventricular (RV) function is even more difficult due to the complex geometry and asymmetry of the right ventricle. Not surprisingly, data on RV function in long-term survivors of childhood malignancies are extremely limited. In an attempt to overcome these limitations, alternative techniques for 3-dimensional reconstruction of the left and right ventricles using multiple echocardiographic planes have been developed, albeit time-consuming and prone to movement artifacts. Furthermore, geometric modeling to translate these multiplanar measurements into volumes is still required. Recently, real-time 3-dimensional (RT3D) or so-called 4-dimensional (4D) echocardiographic technology that allows fast acquisition of data sets encompassing the entire left ventricle and direct quantification of LV volumes and ejection fraction, but without the need for multiplane tracing or geometric modeling, has been introduced. Studies that compared the 2-dimensional and RT3D echocardiographically derived LV volumes in adult cardiac patients with those obtained from cardiac magnetic resonance have shown that RT3D echocardiography allows rapid (<2 minute/patients for data analysis), accurate (correlation coefficient: 0.96, 0.97, and 0.93 for end-diastolic volume, end-systolic volume, and ejection fraction, respectively) and reproducible measurement of LV volumes. Furthermore, RT3D-derived indices of LV volume and function have been validated against reference values obtained from radial long-axis cardiac magnetic resonance images. Apart from derivation of LV volume and function, RT3D echocardiographic technology in the determination of right ventricular (RV) volume and ejection fraction has also recently been validated using cardiac magnetic resonance. While cardiac magnetic resonance is currently considered the reference technique for measuring ventricular volumes and ejection fraction, it remains limited by cost and availability. Serial assessment of ventricular function with radionuclide ventriculography using multigated acquisition is similarly elaborate and expensive. Given the encouraging validation results in adult cardiac patients, we hypothesize that the novel RT3D echocardiographic imaging is useful for the assessment of LV and RV function in long-term survivors of childhood malignancies. To test this hypothesis, the following issues would be addressed in this study: i) feasibility and reproducibility of using RT3D echocardiography in assessing right and left ventricular volumes and systolic function, ii) effect of exercise stress on RT3D-derived right and left ventricular ejection fraction, as compared to age- and sex-matched control subjects, iii) significant determinants of LV and RV systolic function, and iv) relation of arterial dysfunction, demonstrated recently to occur in this patient cohort, on LV systolic function.

Project Title:	Impact of Iron Overload on Left Ventricular Torsion in Patients with β-Thalassaemia Major
Investigator(s):	Cheung YF, Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2008
Completion Date:	12/2009

Abstract:

To test the hypothesis that iron-overloading in patients with beta-thalassaemia major has a negative impact on LV torsional mechanics both at rest and during exercise stress.

Project Title:	Circulating Endothelial and Endothelial Progenitor Cells, Arterial Function, and Ventriculo-Arterial Interaction in Patients with Beta-Thalassaemia Major
Investigator(s):	Cheung YF, Ha SY, Chan GCF, Yang M
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	09/2008

Abstract:

While ventricular dysfunction secondary to iron overload in patients with beta-thalassaemia major is well documented, accumulating evidence suggests coexistence of systemic arterial dysfunction. In these patients, we and others have demonstrated endothelial dysfunction and arterial stiffening as evidenced by reduced brachial arterial flow-mediated dilation, increased stiffness of the carotid artery, ascending aorta, and abdominal aorta, and reduced strain and distensibility of the ascending aorta. Importantly, endothelial dysfunction contributes to arterial stiffening through alteration of the vasomotor tone by reducing availability of endothelium-derived vasodilating substances. With regard to the integrity and functioning of the vascular endothelium, a current theory is that increased number of circulating endothelial cells (CECs) reflects severe endothelial damage and that therefore areas of the denuded subendothelium predisposes to disease processes as atherosclerosis. In parallel is the hypothesis that endothelial progenitor cells (EPCs) are restorative cells that possibly destined to replace or renew damaged areas of the intima. In patients with beta-thalassaemia major, the relationships between circulating endothelial and endothelial progenitor cells, arterial function, and ventriculo-arterial interaction, are hitherto unknown. In vitro studies have provided direct evidence that angiotensin II accelerates onset of EPC senescence via reactive oxygen species production. In a rodent model of iron overload, increased generation of reactive oxygen species within the arterial wall has been similarly demonstrated. Taken together, iron overload in patients with beta-thalassaemia major may potentially lead to disequilibrium between vascular injury and repair. The proposed study is, to the best of our knowledge, the first to quantify both CECs and EPCs simultaneously in patients with beta-thalassaemia major and to determine their relationships with functional indices of arterial and cardiac function. Furthermore, to address the issue of iron overload on levels of CECs and EPCs, these parameters would be compared to those of healthy controls and beta thalassaemia major patients who had undergone bone marrow transplantation and iron depletion therapy. This would also be the first study to use the novel techniques for assessment of endothelial injury, repair, and function in thalassaemia patients after successful bone marrow transplantation. The objectives of the present study are to determine in patients with beta-thalassaemia major: A) the effect of iron overload on quantities of CECs and EPCs and function of EPCs, B) the relationships between levels of CECs and EPCs and indices of arterial function in vivo C) the relationships between indices of left ventricular function and arterial parameters, and D) the impact of bone marrow transplantation followed by phlebotomy on quantities of CECs and EPCs, function of EPCs, and arterial function in vivo

Project Title:	Impact of right ventricular volume overload on left ventricular strain and torsion in patients after surgical repair of tetralogy of Fallot: analysis by novel 3-dimensional speckle tracking echocardiography
Investigator(s):	Cheung YF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	12/2009

Abstract:

Right ventricular dilation occurs commonly after surgical repair of tetralogy of Fallot (TOF) as a result of chronic pulmonary regurgitation. Importantly, significant right ventricular dilation in association with severe chronic pulmonary regurgitation has been shown to be associated with systolic and diastolic dysfunction, ventricular arrhythmias, and impairment of exercise capacity. Although right ventricular dilation and dysfunction have been shown to contribute significantly to long-term morbidity and mortality, left ventricular dysfunction has been found to be independently associated with adverse outcomes in the long-term. While the cause of left ventricular dysfunction is unclear, abnormal ventricular-ventricular interaction has been speculated to be a potential mechanism. Systolic deformation, as quantified by strain, and twisting motion of the left ventricle has been shown to be strong indicators of ventricular performance. In TOF patients, the potential importance of altered left ventricular systolic deformation is suggested by previous finding of delayed systolic myocardial deformation of the septum compared with the lateral wall. Nonetheless, previous assessment of myocardial deformation in these patients was limited to one-dimensional analysis by tissue Doppler imaging, namely the longitudinal dimension, while deformation in the circumferential and radial dimensions was not determined. Indeed, the more sensitive nature of circumferential deformation has been shown recently in adults with myocardial ischaemia. Apart from systolic strain, twisting motion of the left ventricle, so-called torsion, is also known to play an important role with respect to left ventricular ejection and filling and shown to be sensitive to changes to regional and global left ventricular function. Torsional deformation of left ventricle is characterized by systolic twisting and diastolic untwisting along its long axis as a result of the opposite rotation of the cardiac apex and base. Tagged magnetic resonance imaging studies have revealed left ventricular torsion to be a relatively load-independent index of contractility. However, the clinical application of magnetic resonance imaging in the assessment of ventricular torsion has been limited by cost and complexity. The newly introduced three-dimensional speckle tracking echocardiography (STE) enables simultaneous imaging of all segments of the left ventricle and tracking of motion vectors of the speckles in three dimensions from the volume dataset, hence providing complete angle-independent analysis of left ventricular myocardial deformation beyond the two-dimensional scan plane. Additionally, as segments of the left ventricular apex and base are imaged simultaneously, left ventricular torsion can be accurately assessed from one single acquisition. Another advantage of this technique is simultaneous calculation of three-dimensional volumes and ejection fraction. This technique has recently been validated against sonomicrometry in animal models. While ventricular-ventricular interaction has been proposed as a cause of left ventricular dysfunction in patients after surgical repair of TOF, the exact mechanism remains unclear. Advances in three-dimensional echocardiography provide an opportunity to interrogate potentially abnormal ventricular-ventricular interaction from the new perspective of cardiac mechanics. Our recent findings in these patients of relationships between left ventricular mechanical dyssynchrony and severity of pulmonary regurgitation and right ventricular dilation suggest that abnormal myocardial deformation may play a pivotal role mediating abnormal ventricular-ventricular interaction. We therefore hypothesize that right ventricular volume overload is associated with abnormal left ventricular deformation and twisting in patients after surgical repair of TOF. The proposed study is, to our knowledge, the first to quantify left ventricular three-dimensional strain and torsion in patients after TOF repair and to determine the impact of right ventricular volume overload on these indices of deformation. The primary objective of the study is to test the hypothesis that right ventricular volume overload is associated with abnormal left ventricular deformation and twisting in patients after surgical repair of TOF. The issues to be addressed include the followings: i) the effect of right ventricular dilation on left ventricular three-dimensional systolic strain, ii) the effect of right ventricular dilation on left ventricular torsion, iii) the functional implications of abnormal three-dimensional strain and left ventricular torsion in terms of their effects on left ventricular global function and exercise capacity, and iv) the impact of pulmonary valve replacement with reduction of right ventricular volume overload on left ventricular deformation and torsion

Project Title:	Right and Left Ventricular Mechanical Dyssynchrony in Iron Loaded Patients with Beta-Thalassaemia Major
Investigator(s):	Cheung YF, Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2010

Abstract:

1) To test the hypothesis that right ventricular (RV) and LV mechanical dysynchrony occurs in iron loaded patients with beta-thalassaemia major at rest and amplifies during exercise stress; 2) To determine associations between RV and LV mechanical dyssynchrony and global ventricular function as assessed by cardiac magnetic resonance-derived ventricular ejection fraction, myocardial fibrosis, and iron load.

List of Research Outputs

Chen M., Chan S., Yang M., Chan G.C.F. and Cheung Y.F., Travel Award (supervisor of MMed Sc student; Chen Meipian): Iron overload induced apoptosis in HL-1 cardiomyocytes via mitochondria-mediated caspase-3 dependent pathways, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association. Taipei, Taiwan, PR China 2010. . 2010.

Cheung E.W.Y., Liang X., Lam W.W.M. and Cheung Y.F., Impact of right ventricular dilation on left ventricular myocardial deformation in patients after surgical repair of Tetralogy of Fallot, American Journal of Cardiology. 2009, 104: 1264-1270.

Cheung E.W.Y., Wong W.H.S. and Cheung Y.F., Systematic review and meta-analysis of pulmonary valve replacement in children and adults after surgical repair of tetralogy of Fallot, The 6th Korea-Japan-China Pediatric Heart Forum, March 26-27, 2010, Seoul, Korea . 2010.

Cheung Y.F., 'Vascular Failure' in Kawasaki Disease , The 5th China-Korea-Japan Pediatric Heart Forum, Sept 10 - 11, 2009, Beijing, China . 2009.

Cheung Y.F., Arterial function in the young: assessment, determinants and implications, Chinese Paediatric Cardiology Conference. Chongqing, China 2010. 2010.

Cheung Y.F., Arterial stiffness in the young:assessment, determinants, and implications, Korean Circ J . 2010, 40: 153-162.

Cheung Y.F., Cardiovascular health in patients with Thalassaemia and Kawasaki Disease, the 5th Workshop of Asian Hematology NRCT-JSPS Asian Core Program, Queen Mary Hospital, Hong Kong . 2009.

Cheung Y.F., Effect of Iron Chelation Therapy on Arterial Function and Carotid Stiffness, Asian Pacific Iron Academy Conference, Chiang Mai, Thailand . 2009.

Cheung Y.F., International Editorial Board member, Second Editorial Committee, World Journal of Pediatrics , 2010.

Cheung Y.F., Hong W., Chan G.C.F., Wong S.J. and Ha S.Y., Left ventricular myocardial deformation and mechanical dyssychrony in chidlren with normal ventricular shortening fraction after anthracyline therapy , The 6th Korea-Japan-China Pediatric Heart Forum, March 26-27, Seoul, Korea. 2010.

Cheung Y.F., Management of Pulmonary Atresia with Intact Ventricular Septum , International Congress of Cardiology, Hong Kong . 2010.

Cheung Y.F., Liang X., Chan G.C.F., Wong S.J. and Ha S.Y., Myocardial deformation in patients with beta-thalassemia major: a speckle tracking echocardiographic study , Echocardiography. 2010, 27: 253-259.

Cheung Y.F., Paediatric Clinical Research in Hong Kong - Opportunities and Challenges - presented to the meeting of Editorial Board Member of Chinese Journal of Evidence-based Pediatrics. Children's Hospital of Fudan University, Shanghai, China, 2010, 2010.

Cheung Y.F., Public lecture series: 'Minimally Invasive Catheter Interventions for Congenital Heart' - presented to Hong Kong, Hong Kong Central Library , 2009.

Cheung Y.F., Cheung E.W.Y. and Wong W.H.S., Systematic review and meta-analysis of pulmonary valve replacement in children and adults after surgical repair of tetralogy of Fallot, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association. Taipei, Taiwan, China 2010. . 2010.

Cheung Y.F., Systemic Circulation. In Anderson, Baker, Penny, Redington, Rigby, Wernovsky (Eds). Paediatric Cardiology. , Elsevier, 2009, 91-116.

Cheung Y.F., Ventricular-Ventricular Interaction in Patients After Repair of Tetralogy of Fallot , The 12th South China International Congress of Cardiology, Guangzhou, PR China, 8 - 11 April 2010 . 2010.

Cheung Y.F., Workshop for new academic staff: “How to get my first GRF grant” – presented to Li Ka Shing Faculty of Medicine, Hong Kong, 2010., 2010.

Cheung Y.F., 張耀輝. 川崎病 (Kawasaki Disease). 第十三章第三節冠狀動脈及全身動脈功能障礙及與早發動脈粥樣硬化的關係. , 科學技術文獻出版社, 2009, 214-227.

Hong W., Yung T.C., Lun K.S., Wong S.J. and Cheung Y.F., Impact of right ventricular pacing on three-dimensional global left ventricular dyssynchrony in children and young adults with congenital and acquired heart block associated with congenital heart disease , The American Journal of Cardiology. 2009, 104: 700-706.

Hong W., Yung T.C., Lun K.S., Wong S.J. and Cheung Y.F., Impact of temporary interruption of right ventricular pacing for heart block on left ventricular function and dyssynchrony. , Pacing and Clinical Electrophysiology. 2010, 33: 41-48.

Ko L.Y., Chau A.K.T., Yung T.C., Cheung Y.F. and Lun K.S., Retrospective Review on Anomalous Left Coronary Artery from Pulmonary Artery , Hong Kong Journal of Paediatrics . 2010, 15: 12-18.

Koh C., Lee P.P.W., Yung T.C., Lun K.S. and Cheung Y.F., Left ventricular noncompaction in children, Cogenital Heart Disease. 2009, 4: 288-294.

Li X., Cheng L.C., Cheung Y.F., Lun K.S., Chau A.K.T. and Chiu S.W., Management of symptomatic congenital tracheal stenosis in neonates and infants by slide tracheoplasty: a 7-year single institution experience, European Journal of Cardio-thoracic Surgery. 2010, Epub ahead of print.

Liang X., Lam W.W.M., Cheung E.W.Y., Wu A.K.P., Wong S.J. and Cheung Y.F., Restrictive Right Ventricular Physiology and Right Ventricular Fibrosis as Assessed by Cardiac Magnetic Resonance and Exercise Capacity After Biventricular Repair of Pulmonary Atresia and Intact Ventricular Septum , Clinical Cardiology . 2010, 33: 104-110.

Lun K.S., Fan K., Yung T.C., Wong K.T., Cheung Y.F., Chau A.K.T. and Cheng L.C., Experience of pediatric heart transplantation in Hong Kong, International Congress of Cardiology, Hong Kong, 26-28 February 2010.

Lun K.S., Fan K., Wong C.F., Yung T.C., Chow P.C., Wong K.T., Cheung Y.F., Chow W.H., Chau A.K.T., Chiu S.W. and Cheng L.C., Outcome of thoracic organ transplantation for adults with congenital heart disease, 18^th Annual Scientific Congress, Hong Kong College of Cardiology, Hong Kong, 14-16 May 2010.

Tsang F.H.F., Li X., Cheung Y.F., Chau A.K.T. and Cheng L.C., Pulmonary valve replacement after surgical repair of Tetralogy of Fallot, Hong Kong Medical Journal . 2010, 16: 26-30.

Researcher : Chiang AKS

Project Title:	Genetic studies of tubercubosis
Investigator(s):	Chiang AKS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	03/2002

Abstract:

To host susceptibility genes in tubercubosis; to study pharmacogenomics in anti-tubercubosis drug metabolism.

Project Title:	Prospective study of virologic and immunologic parameters of primary Epstein-Barr virus infection in Chinese children
Investigator(s):	Chiang AKS, Chan KH
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2003

Abstract:

An unresolved issue in EBV immunology concerns the relationship between clinical IM-like symtoms, virus DNA load and CD8+ T cell lymphocytosis; Acute IM in adolescents is associated with large expansions of EBV lytic epitope reactivities which are followed by a later expansion of latent epitope responses. The magnitude of the EBV lytic and latent epitope reactivities would be studied and compared in both IM and non-IM patients; likewise, is there a difference in the rate of emergence of latent epitope responses bewteen the IM and non -IM patients? The kinetics and evolution of the EBV epitope-specific cytotoxic T-lymphocyte (CTL) responses from primary to persistent phases of EBV infection would be compared between the two groups of children.

Project Title:	Prospective study of Epstein-Barr virus (EBV) strains in primary EBV infection
Investigator(s):	Chiang AKS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To study the occurrence of Epstein-Barr virus (EBV) diversity and coinfection in a prospective study of primary Epstein-Barr virus infection in Chinese children.

Project Title:	Longitudinal study of Epstein-Barr virus specific antibody responses in childhood infectious mononucleosis
Investigator(s):	Chiang AKS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	12/2005

Abstract:

The purpose of the proposed study is to compare the evolution of Epstein-Barr virus (EBV) specific antibody responses in a longitudinal followup study of symptomatic and asymptomatic primary EBV infection. What is known about EBV antibody responses in the literature? Epstein-Barr virus (EBV) infects greater than 90% of all human populations and establishes a lifelong persistence within the host. Primary infections by EBV may remain silent or induce a self-limiting lymphoproliferative disorder, infectious mononucleosis (IM). EBV-encoded antigens are divided into those expressed in the viral replicative cycle, i.e., the viral capsid antigen (VCA) and the early amtigens (EA) of the diffuse (D) and the restricted (R) varieties and those expressed in the viral latent cycle, the EBV-determined nuclear antigen (EBNA). The different timing of emergence between the antibodies to VCA and EA and those to EBNA indicates that the two sets of antigens are likely expressed on separate types of cells which become available to stimulate antibody responses under different circumstances. The laboratory diagnosis of EBV infection is based on serological tests to detect both specific antibodies to EBV antigens (1, 2) and heterophile antibodies (3, 4). At the onset of symptoms of IM, the humoral response to EBV infection is characterized by the presence of VCA IgM antibodies and the concurrent rise of VCA IgG antibodies (5). Antibodies to diffuse early antigen (anti-EA-D) are transitory and are detected in about 80% of infected persons. Antibodies to EA-R may become detectable in protracted cases of the disease after the anti-D titres have subsided. Anti-EBNA IgG can usually be detected at a later stage at several weeks to months after the the onset of symptoms. The majority of adult IM patients also develop IgM heterophile antibodies of the Paul-Bunnell type but the reason for their transient emergence is unknown. However, these heterophile antibodies are absent in the majority of children under 4 years of age (6). The antibody responses in silent primary EBV infections (more frequently occurred in children than adults) largely conform to those seen in IM except that antibodies to the EA complex are directed against R instead of D (7, 8). The early EBV-specific IgG antibody response after primary infection is made up of low avidity antibodies. The avidity increases in the few weeks to several months after the infection (9, 10). This property of the humoral IgG response has been employed in serological assays to distinguish between primary and re-infection or reactivation of different viruses such as rubella, CMV and parvovirus (11, 12, 13). Key issues: The pattern of antibody responses and the antibody levels to EBV-encoded antigens are largely derived from cross sectional studies of large number of individuals. Longitudinal serology data of persons recovering from IM is seldom available and information on the humoral response in asymptomatic EBV infection is scanty. I have followed a large number of Chinese children presenting with infectious mononucleosis and some children who are found to have asymptomatic primary EBV infection from the time of onset of infection through convalescence to persistence. It offers an opportunity to compare the natural evolution of antibody responses against EBV in symptomatic and asymptomatic infections. Project objectives: 1. To define the evolution of the humoral response against a human persistent virus. 2. To study the maturation of the humoral response against a persistent virus in terms of antibody avidity. 3. To compare the magnitude and the quality of the humoral response against viral lytic and latent EBV antigens from acute phase through convalescent to persistent phase in symptomatic and asymptomatic infections. References: 1.Henle W and Henle G: Epstein-Barr virus specific serology in immunologically compromized individuals. Cancer Res 41: 4222-4225, 1981 2.Henle W and Henle G: Immunology of Epstein-Barr virus. In: B, Roizman (Ed.), The Herpsesviruses, Vol. 1. Plenum Publishing Corp., Ne York, pp 209-252, 1982 3.Paul JR and Bunnell WW: The presence of heterophile antibodies in infecetious mononucleosis. Am J Med Sci 183: 90-104, 1932 4.Davidsohn I and Lee CL: The clinical serology of infectious mononucleosis. In: RL Carter and HG Penman (Eds.), Infectious Mononucleosis. Blackwell Scientific Publications, Ltd., Oxford, pp 177-200, 1969 5.Okano M, Thiele GM, Davis JR, Grierson HL, Purtilo DT: Epstein-Barr virus and human diseases: recent advances in disgnosis. Clin Microbiol Rev 1: 300-312, 1988 6.Sumaya CV: Infectious mononucleosis and other EBV infections: diagnostic factors. Lab Manag 24: 37-45, 1986 7.Biggar RJ, Henle G, Bocker J, Lennette ET, Fleisher G, Henle W: Primary Epstein-Barr virus infections in African infacnts. II. Clinical and serological obsevations during seroconversion. Int J cancer 22: 244-250, 1978 8.Fleisher G, Henle W, Henle G, Lennette ET, Biggar RJ: Primary Epstein-Barr virus infection in American infants: clinical and serological observations. J Infect Dis 139: 553-558, 1979 9.Inouye S, Hasegawa A, MAtsuno S, Katwo S: Changes in antibody avidity after virus infections: detection by an immunosorbent assay in which a mild protein-denaturing agent is employed. J Clin Microbiol 20: 525-529, 1984 10.Kocks C and Rajewsky K: Stepwise intracloncal maturation of antibody affinity through somatic hypermutation. Proc Nat Acad Sci USA 85: 8206-8210, 1988 11.Thomas HIJ and Morgan-Capner P: Rubella-specific IgG subclass avidity and its role in differenetiation between primary rubella and rubella reinfection. Epidemiol Infect 101: 591-598, 1988 12.Lutz E, Ward KN, Gray JJ: Maturation of antibody avidity after primary human cytomegalovirus infection is delayed in immunosuppressed solid organ transplant patients. J Med Virol 44: 317-322, 1994 13.Gray JJ, Cohen BJ, Dresselberger U: Detection of human parvirus B19-specific IgM and IgG sntibodies using a recombinant viral VP1 antigen expressed in insect cells and estimation of time of infection by testing for antibody avidity. J Virol Methods 44: 11-24, 1993

Project Title:	Longitudinal study of phenotypic changes and functionality of Epstein-Barr virus (EBV)-specific CD8+ T cell responses in symptomatic and asymptomatic EBV infection
Investigator(s):	Chiang AKS, Chan KH
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2007

Abstract:

To study: (1)characterization of EBV-specific CD8+ T cell phenotypes in IM and AS patients over time. (2)characterization of EBV-specific CD8+ T cell functions in IM and AS patients over time. (3)correlation of phenotype, functionality and viral loads in IM and AS patients over time.

Project Title:	Activation of Epstein-Barr virus (EBV) in EBV-associated malignancy
Investigator(s):	Chiang AKS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	01/2008
Completion Date:	01/2010

Abstract:

Background: Finding agents that specifically affect cancer cells without damaging normal cells has long been an important goal in cancer treatment. About 15% of all human cancers are virally associated. In Epstein-Barr virus (EBV)-associated cancers, every tumor cell was latently infected with EBV. However, very few viral proteins are expressed and anti-viral drugs do not kill the virally infected tumour cells. Our basic premise is to find novel ways to reactivate EBV within the tumour cells into lytic cycle where many more viral proteins will be expressed and hence provide new treatment targets. Different patterns of latent EBV gene expression are observed. In latency III (e.g. post-transplant lymphoprolifeartive disease [PTLD]), nine latent viral proteins and two small RNAs (the EBER RNAs) are expressed. In latency II (e.g. Hodgkin disease and nasopharyngeal cancer [NPC]), only EBNA-1, LMP-1, LMP2A and the EBER RNAs are expressed. In latency I (e.g. Burkitt lymphoma), only EBNA-1 and the EBER RNAs are expressed. The viral gene expression in lytic cycle follows a sequential order. The immediate early genes are first expressed, followed by the early genes and then the late genes. BZLF expression is commonly used as an indicator of induction of EBV lytic cycle (1). Certain chemotherapeutic agents were shown to have the ability to induce lytic viral gene expression in various cell lines. For instance, 5-fluorouracil (5-FU), cisplatinum, and methotrexate induced lytic gene expression in EBV-positive epithelial cell tumors; gemcitabine, doxorubin, and methotrexate induced lytic gene expression in EBV-positive B cell (2). The mechanism of lytic viral genes expression induced by these chemotherapy drugs is still unclear. The effect of lytic cycle induction by chemotherapy is very weak. However, stronger chemotherapy killing of EBV-transformed B cells was achieved by co-administrating the chemotherapy with ganciclovir (3). The lytic cycle of EBV in Burkitt lymphoma (BL) cell line can be induced by cross-linking the surface immunoglobulin (B cell receptor) by an anti-Ig antibody, so as to mimic the binding of antigen to the BCR. This is the most effective way to induce the lytic cycle of EBV in vitro. The lack of expression of LMP2A in latency I is important for reactivation of EBV via BCR, since the expression of LMP2A protein in latency II and latency III was shown to block the signal transduction via the BCR (4). Histone deacetylase inhibitors (HDACI) such as n-butyrate and trichostatin A (TSA) can induce the lytic cycle of EBV in a BL cell line but not in a lymphoblastoid cell line (LCL). In contrast, a phorbol ester tetradecanoyl phorbol acetate (TPA) can induce the lytic cycle of EBV in the LCL but not the BL cell line (5). HDAC inhibitors cause accumulation of acetylation. The positive charge on histones is neutralized by acetylation resulting in a more open conformation of chromatin, which enhances access of the transcription apparatus to promoter regions of DNA (6). The mechanism of how the HDAC inhibitors work is largely unknown. It is possible to combine antiviral drugs (e.g. gancyclovir) to kill the EBV+ cells following lytic cycle induction by the HDAC inhibitors, without affecting the normal cells. This is because the virally encoded kinases (thymidine kinase and BGLF4), which are expressed only during the lytic cycle of EBV, can convert the antiviral drugs into their cytotoxic form. An effective method to induce the lytic cycle of EBV in tumour cells is still lacking. Moreover, the molecular mechanism underlying the HDACI-induced EBV reactivation remains unclear. It is interesting to characterize the effects of a panel of HDACI on EBV positive tumor cells and to investigate the combined effect with antiviral drugs. Project objectives: 1. Establishing cell culture models of EBV-associated malignancy: Some background work has already been carried out by Dr. Alan Chiang (Paediatrics) in establishing stable transfectants of EBV-positive cancer cell lines of latency I, II and III (three forms of latency found in EBV-related cancers). The transfected lines harbour a luciferase reporter plasmid containing a critical EBV lytic gene promoter. 2. Induction of lytic cycle of EBV by histone deactylase inhibitors (HDACI): HDACI de-repress genes that can mediate growth inhibition and apoptosis of cancer cells. Combination of different classes of HDAC inhibitors, some of which are already in clinical use, will be tested on EBV-positive cell lines of latency I, II and III for induction of EBV lytic cycle. Optimal testing conditions in 96-well format are established. 3. Development of novel therapeutic strategies: Our research strategy is to identify combination of HDACI which can be used in clinically relevant concentrations to effectively switch on critical EBV lytic gene regulator. We aim at effecting progression to late lytic gene products such as EBV thymidine kinase which can phosphorylate anti-viral drug, such as ganciclovir, mediating specific tumour cell killing. Mechanisms of viral gene induction by interesting compounds will be intensely studied in terms of EBV gene function and signaling. References: 1. Wolfgang Amon and Paul J. Farrell*. 2004. Reactivation of Epstein-Barr virus from latency. Rev. Med. Virol. 15. p. 149–156. 2. Wen-hai Feng and Shannon C. Kenney. 2006. Valproic Acid Enhances the Efficacy of Chemotherapy in EBV-Positive Tumors by Increasing Lytic Viral Gene Expression. Cancer Res, p. 8762–8769 3. Feng W-H, Hong G, Delecluse HJ, Kenney SC. 2004. Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas. J Virol, 78, p. 1893–902. 4. Takada K. 1984. Cross-linking of cell surface immunoglobulins induces Epstein-Barr virus in Burkitt lymphomalines. Int J Cancer. 33. p. 27–32. 5. Lyndle Gradoville, David Kwa, Ayman El-Guindy and George Miller. 2002. Protein Kinase C-Independent Activation of the Epstein-Barr Virus Lytic Cycle. Virology, p. 5612–5626 6. David M Vigushin and R Charles Coombes. 2002. Histone deacetylase inhibitors in cancer treatment. Anti-Cancer Drugs, 13, p. 1–13

Project Title:	Sequence analysis of Epstein-Barr virus strains in nasopharyngeal carcinoma
Investigator(s):	Chiang AKS, Kwong DLW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	12/2008

Abstract:

(1) Characterization of EBV strains in NPC tumours and matched non-tumour tissues (PBMC, plasma and saliva) using an extended panel of polymorphic markers; (2) Characterization of EBV strains in PBMC, plasma and saliva of children with primary EBV infection and long term carriers of the same geographic and ethnic population; (3) Sequence analysis of whole genome of NPC-specific EBV strains to identify genetic differences between NPC and prototype strains.

Project Title:	Tracking CD4 and CD8 positive virus-specific polyfunctional T cells in Epstein-Barr virus infection
Investigator(s):	Chiang AKS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	12/2009

Abstract:

Background: Activated T lymphocytes are the most important effector cells to control viral infection through secretion of functional cytokines, chemokines and cytotoxic molecules, such as IFN-γ, TNF-α, IL-2, granzyme B and perforin. Recently, increasing evidence points to the correlation of polyfunctional T cells (PFCs), which are capable of producing multiple cytokines and chemokines or having cytotoxic function or proliferative capability, to protective immunity [1]. With the advent of polychromatic flow cytometry technology, it is now possible to perform multi-color staining [2-4]. To date, PFCs have been detected in HIV [5, 6], cytomegalovirus (CMV) [7], hepatitis B virus (HBV) [8], hepatitis C virus (HCV) [5, 9] and after smallpox vaccinations [10]. PFCs seem to have more important roles in controlling viral infections than those of single functional T cells. One landmark study tested five functions, CD107a, IFN-γ, TNF-α, IL-2, and MIP-1β, simultaneously in HIV specific T cells [6]. The study showed that HIV non-progressors have more PFCs than those of progressors, and high frequency of PFCs is significantly related to lower viral loads in non-progressors [11]. Epstein-Barr virus (EBV) is a herpes virus which infects and persists in the majority of human populations. The primary infection may cause no symptoms or a self-limiting condition known as infectious mononucleosis. In Hong Kong, most of the primary infections occur in children [12]. T cells play key roles in controlling EBV at both acute and persistent phases of infection [13-15] and both CD4 and CD8 T cells are thought to be important. In primary infection, both lytic and latent EBV-specific CD4 and CD8 T cells are detectable in blood [15]. Among the lytic proteins, CD8 T cells have strongest response to BZLF1 protein [15, 16] whilst CD4 T cells can recognize late lytic proteins [17, 18]. Among the latent proteins, the hierarchical order of CD8 T cell responses is to EBNA3 and LMP2 proteins whilst that of CD4 T cell response is to EBNA1 and EBNA3 proteins. In contrast to HBV, HCV and HIV, EBV-specific T cells seem to have greater ability to control the virus. Little work is performed to characterize EBV-specific polyfunctional T cells, how they develop and their roles in primary and persistent infection. In a previous study, by using single EBV protein derived peptide stimulation, we have confirmed EBV specific polyfunctional CD8 T cells are detectable in primary infection, and these polyfunctional CD8 T cells have stable proportion in memory pool over time. Furthermore, EBV specific CD8 polyfunctional T cells have 3-5 fold higher IFN-γ secretion than those of non-polyfunctional CD8 T cells. However, there are still important gaps in the understanding of PFCs in EBV infection and this study hopes to address these areas in greater detail. Specific aims of this study: 1. Individual epitope-specific CD8 T cells do not represent total immune response derived from that protein. In this project, we are using overlapping peptides of the entire protein which will cover all the immuno-genetic peptides of that protein and may yield potent responses both from CD4 and CD8 positive T cells. The following latent proteins (EBNA1, LMP2, EBNA3A) and lytic protein (BZLF1) will be investigated. 2. We are investigating cytotoxic and proliferative functions by CD107a and CFSE staining, respectively, in addition to cytokine and chemokine (IFN-γ, MIP-1α, TNF-α, IL-2) production. This will give us a more robust definition of the polyfunctional T cells (both CD4 and CD8) as those that secrete three of four cytokines and are cytotoxic and proliferative. 3. We can perform a longitudinal study tracking the changes in CD4 and CD8 positive T cells during acute and persistent phases of EBV infection in our unique cohort of patients. References: 1. Betts MR, Harari, A: Phenotype and function of protective T cell immune responses in HIV [Immune correlates of protection, activation and exhaustion: Edited by Richard Koup and Giuseppe Pantaleo]. Current Opinion in HIV and AIDS 2008, 3(3):349-355. 2. Chattopadhyay PK, Price DA, Harper TF, Betts MR, Yu J, Gostick E, Perfetto SP, Goepfert P, Koup RA, De Rosa SC et al: Quantum dot semiconductor nanocrystals for immunophenotyping by polychromatic flow cytometry. Nat Med 2006, 12(8):972-977. 3. Mahnke YD, Roederer M: Optimizing a multicolor immunophenotyping assay. Clin Lab Med 2007, 27(3):469-485, v. 4. Perfetto SP, Chattopadhyay PK, Roederer M: Seventeen-colour flow cytometry: unravelling the immune system. Nat Rev Immunol 2004, 4(8):648-655. 5. Rehr M, Cahenzli J, Haas A, Price DA, Gostick E, Huber M, Karrer U, Oxenius A: Emergence of polyfunctional CD8+ T cells after prolonged suppression of human immunodeficiency virus replication by antiretroviral therapy. J Virol 2008, 82(7):3391-3404. 6. Betts MR, Nason MC, West SM, De Rosa SC, Migueles SA, Abraham J, Lederman MM, Benito JM, Goepfert PA, Connors M et al: HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 2006, 107(12):4781-4789. 7. Casazza JP, Betts MR, Price DA, Precopio ML, Ruff LE, Brenchley JM, Hill BJ, Roederer M, Douek DC, Koup RA: Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation. J Exp Med 2006, 203(13):2865-2877. 8. De Rosa SC, Lu FX, Yu J, Perfetto SP, Falloon J, Moser S, Evans TG, Koup R, Miller CJ, Roederer M: Vaccination in humans generates broad T cell cytokine responses. J Immunol 2004, 173(9):5372-5380. 9. Ciuffreda D, Comte D, Cavassini M, Giostra E, Buhler L, Perruchoud M, Heim MH, Battegay M, Genne D, Mulhaupt B et al: Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication. Eur J Immunol 2008, 38(10):2665-2677. 10. Precopio ML, Betts MR, Parrino J, Price DA, Gostick E, Ambrozak DR, Asher TE, Douek DC, Harari A, Pantaleo G et al: Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T cell responses. J Exp Med 2007, 204(6):1405-1416. 11. Duvall MG, Precopio ML, Ambrozak DA, Jaye A, McMichael AJ, Whittle HC, Roederer M, Rowland-Jones SL, Koup RA: Polyfunctional T cell responses are a hallmark of HIV-2 infection. Eur J Immunol 2008, 38(2):350-363. 12. Chan CW, Chiang AK, Chan KH, Lau AS: Epstein-Barr virus-associated infectious mononucleosis in Chinese children. Pediatr Infect Dis J 2003, 22(11):974-978. 13. Callan MF, Annels N, Steven N, Tan L, Wilson J, McMichael AJ, Rickinson AB: T cell selection during the evolution of CD8+ T cell memory in vivo. Eur J Immunol 1998, 28(12):4382-4390. 14. Callan MF, Steven N, Krausa P, Wilson JD, Moss PA, Gillespie GM, Bell JI, Rickinson AB, McMichael AJ: Large clonal expansions of CD8+ T cells in acute infectious mononucleosis. Nat Med 1996, 2(8):906-911. 15. Precopio ML, Sullivan JL, Willard C, Somasundaran M, Luzuriaga K: Differential kinetics and specificity of EBV-specific CD4+ and CD8+ T cells during primary infection. J Immunol 2003, 170(5):2590-2598. 16. Callan MF: The evolution of antigen-specific CD8+ T cell responses after natural primary infection of humans with Epstein-Barr virus. Viral Immunol 2003, 16(1):3-16. 17. Neuhierl B, Feederle R, Adhikary D, Hub B, Geletneky K, Mautner J, Delecluse HJ: Primary B-cell infection with a deltaBALF4 Epstein-Barr virus comes to a halt in the endosomal compartment yet still elicits a potent CD4-positive cytotoxic T-cell response. J Virol 2009, 83(9):4616-4623. 18. Amyes E, Hatton C, Montamat-Sicotte D, Gudgeon N, Rickinson AB, McMichael AJ, Callan MF: Characterization of the CD4+ T cell response to Epstein-Barr virus during primary and persistent infection. J Exp Med 2003, 198(6):903-911.

List of Research Outputs

Cheuk D.K.L., Chiang A.K.S., Chan G.C.F. and Ha S.Y., Urate oxidase for the prevention and treatment of tumor lysis syndrome in children with cancer, Cochrane Database Syst Rev. 2010;6:CD006945. 2010, 6: 1-48.

Chiang A.K.S., Clinical experience with clofarabine in management of leukaemia in Hong Kong children., Evoltra China Hematology AB Meeting, Changsha, Hunan, China, 16 May. 中國血液學專家顧問會議, 2010.

Chiang A.K.S., Clinical spectrum of post-transplant lymphoproliferative disorder., HM Lui Memorial Fund Liver Lecture series, University of Hong Kong, Hong Kong, 12 January, 2010. 2010.

Chiang A.K.S., Diagnosis and treatment of paediatric solid tumours (香港兒童實體腫瘤的診斷和治療), 香港兒童實體腫瘤的診斷和治療, The National Continuing Medical Education Class—Hot-points and Difficulties in the Clinical Research of Pediatric Hematology/Oncology Disease, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China (兒童血液/腫瘤疾病臨床研究熱點及難點, 上海交通大學醫學院附屬新華醫院兒童血液/腫瘤科, 上海中國) 23-24 May. 兒童血液/腫瘤疾病臨床研究熱點及難點, 上海交通大學醫學院附屬新華醫院兒童血液/腫瘤科, 上海中國, 2010.

Chiang A.K.S., EBV and lymphoma., The 5th Workshop of Asian Hematology, National Research Council of Thailand, Japan Society for the Promotion of Science and Dept of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, November 24, 2009. 2009.

Chiang A.K.S., Epstein-Barr virus and lymphoma., 5th Worrkshop of Asian Hematology, National Research Council of Thailand and Japan Society for the Promotion of Science, Hong Kong, 24 November. 2009.

Chiang A.K.S., Post-transplant lymphoproliferative disease , Grand Round, Dept of Ophthalmology, The University of Hong Kong on 26 April. 2010.

Chiang A.K.S., 小兒淋巴瘤知多少, 小兒淋巴瘤知多少, Highlight of the day, Apple Daily (蘋果日報健康與醫療-兒時故事) January 6. 蘋果日報健康與醫療-兒時故事, 2010.

Ha S.Y., Mok S.P., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*. , Hemoglobin. 2009, 33(5): 323-331.

Ha S.Y., Mok S.P., Chu W.C.W., Rasalkar D.D., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*., Hemoglobin (Proceedings of the 17th International Conference on Chelation (ICOC), Shenzhen, PR China 23-27 November 2007).. 2009, 33(5): 323-331.

Hui K.F. and Chiang A.K.S., Suberoylanilide hydroxamic acid (SAHA) induces viral lytic cycle in Epstein-Barr Virus-positive epithelial malignancies and mediates enhanced cell death, 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong, 2-3 December. 2009.

Hui K.F. and Chiang A.K.S., Suberoylanilide hydroxamic acid (SAHA) induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death, 6th Hong Kong International Cancer Congress, LKS Faculty of Medicine, The University of Hong Kong, 4-6 November. 2009.

Hui K.F., Tsao G.S.W. and Chiang A.K.S., Suberoylanilide hydroxamic acid induces Epstein-Barr virus lytic cycle and enhanced apoptosis in nasopharyngeal carcinoma, 101st Annual Meeting of American Association for Cancer Research, Washington, DC, USA, 17-21 April. 2010.

Hui K.F. and Chiang A.K.S., Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death., International Journal of Cancer 126:2479-2489. 2010.

Researcher : Chik SCC

List of Research Outputs

Lee D.C.W., Yang L.H., Chik S.C.C., Li C.B. and Lau A.S.Y., Bioactivity-guided identification and cell signaling analysis to investigate the immunomodulatory effects of ginseng on U937 cells., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP2-046]. 2009.

Lee D.C.W., Yang L.H., Chik S.C.C., Li J., Rong J., Chan G.C.F. and Lau A.S.Y., Immunomodualtory effect of Panax ginseng on human promonocytic U937 cells, Journal of Translational Medicine. 2009, 7: 34-40.

Yang L.H., Wang L., Or C.T., Chik S.C.C., Li C.B. and Lau A.S.Y., Anti-inflammatory compounds from medicinal herbs capable of modulating cytokines expression in human primary blood macrophages, Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-088]. 2009.

Yang L.H., Chik S.C.C., Li C.B., Cheung B.K.W. and Lau A.S.Y., Anti-inflammatory mechanisms of black cohosh on human primary blood macrophages via its downregulation of signal transduction and transcription factor activation., 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM), Nottingham, UK, August 26-28, . 2009.

Researcher : Chim S

List of Research Outputs

Wong S.N., Chan W.K.Y., Hui J., Chim S., Lee T.L., Lee K.P., Leung L.C.K., Tse N.K.C. and So Y.F., Membranous lupus nephritis in Chinese children - a case series and review of the literature, Pediatric Nephrology. 2009, 24: 1989-1996.

Researcher : Chiu RPH

List of Research Outputs

Wong H.T., Chiu R.P.H. and Chan S.Y., A role of TSPYL2, a novel nucleosome assembly protein, in transcriptional regulation, The British Association for Cancer Research/The European Association for Cancer Research, Chromatin and Cancer Symposium, Cambrigde, UK, 6-8 Julyy 2009.

Researcher : Chiu SSS

Project Title:	Streptococcus pneumoniae carriage in young children in Hong Kong
Investigator(s):	Chiu SSS, Ho PL
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Health Services Research Fund - Full Grants
Start Date:	10/1999

Abstract:

To study the serotypes and the incidence of antibiotic resistant Streptococcus pneumoniae in young children in the community.

Project Title:	A comparison study of humoral and cellular immune responses in very young infants after intradermal versus intramuscular injection of influenza vaccine
Investigator(s):	Chiu SSS, Lau YL, Peiris JSM, Tu W
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	07/2007

Abstract:

To determine serum influenza haemagglutinin inhibition and neutralization antibody responses in young infants after administrations of intradermal versus intramuscular vaccination. We hypothesize that intradermal influenza vaccination elicits a better hemagglutination antibody (HAI) titer and microneutralization (NI) antibody response when compared to intramuscular vaccination. Specifically, we hypothesize that intradermal vaccination results in at least 30% improved immunogenicity over that of intramuscular of the same vaccine at the same dose in infants; to determine the primary influenza virus-specific CD4 and CD8 T cell responses in young infants after administrations of intradermal versus intramuscular vaccination. We hypothesize that young infants will have a delayed and reduced appearance of influenza virus-specific CD4 T cells capable of producing Th1 cytokines (IFN-gamma and TNF-alpha) and expressing CD154, but have a robust influenza A virus-specific CD8 T cells. We further hypothesize that intradermal vaccination will induce better primary influenza virus-specific CD4 and CD8 T cell responses than intramuscular vaccination; to determine the number, phenotype and functions of influenza virus-specific memory/ effector CD4 and CD8 T cells in young infants after administrations of intradermal versus intramuscular vaccination. We hypothesize that young infants have detectable influenza virus-specific memory and effector CD4 and CD8 T cell responses as defined by multiple phenotypic markers and effector functions, and intradermal vaccination induces better influenza virus-specific memory and effector CD4 and CD8 T cells responses 3 weeks after the 2nd dose of vaccination.

List of Research Outputs

Chiu S.S.S., 17^th Infection Control Course for Health Care Professionals 2010, Asia Pacific Society of Infection Control, World Health Organization Collaborating Centre for Infection Control, Infectious Disease Centre of Hospital Authority and the Squina International Centre for Infection Control of the HK Polytechnic University, HK, 15-27 March 2010.

Chiu S.S.S., Chan K.H., Tu W., Lau Y.L. and Peiris J.S.M., Immunogenicity and safety of intradermal versus intramuscular route of influenza immunization in infants less than 6 months of age: a randomized controlled trial, Vaccine. 2009, 27(35): 4834-9.

Chiu S.S.S., Reviewer, Journal of Medical Virology. 2010.

Chiu S.S.S., Chan K.H., Chen H., Young B.W., Lim W., Wong W.H.S., Lau Y.L. and Peiris J.S.M., Virologically confirmed population-based burden of hospitalization caused by influenza A and B among children in Hong Kong, Clinical Infectious Diseases. 2009, 49: 1016-1021.

Chiu S.S.S., 兒童流感面面觀, 育醫造才:探索醫學世界, 香港大學李嘉誠醫學院, 2010, 43-45.

Cowling B.J., Leung G.M., Riley S., Ip D.K.M., Chiu S.S.S., Peiris J.S.M. and Chan K.H., A randomized controlled trial of the effectiveness of FluMist® vaccine in school aged children to reduce infection and transmission of influenza in children and their households (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 21.

Cowling B.J., Chiu S.S.S., Chan K.H., Peiris J.S.M. and Leung G.M., A randomized controlled trial of the effectiveness of vaccinating children to reduce household transmission of influenza (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong. Hong Kong, School of Public Health/HKU, 2009, 20.

Garcia J., Pepin S., Lagarde N.J.C., Ma S.K., vogel F.R., Chan K.H., Chiu S.S.S. and Peiris J.S.M., Heterosubtype neutralizing responses to influenza A (H5N1) viruses are mediated by antibodies to virus haemagglutinin, PLoS One. 2009, 4(11): e7918.

Lo W.U., Ho P.L., Chow K.H., Lai E.L.Y., Yeung F. and Chiu S.S.S., Fecal carriage of CTXM type extended-spectrum beta-lactamase-producing organizms by children and their household contacts, Journal of Infection. 2010, 60: 286-292.

Ng S., Cowling B.J., Chan K.H., Chiu S.S.S., Peiris J.S.M. and Leung G.M., A randomized controlled trial of the effectiveness of vaccinating children to reduce household transmission of influenza (Poster presentation), 14th Research Postgraduate Symposium, 2-3 December 2009, Hong Kong. Hong Kong, LKS Faculty of Medicine, HKU, 2009, 86.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Wong C.M., Chiu S.S.S., Yang L., Wong T.W., Ma S., He J.F., Chen P., Chan K.P., Chan K.H., Wong W.H.S. and Peiris J.S.M., The burden of seasonal influenza in Hong Kong: A model-based approach with validation and comparison with other tropical/subtropical cities (poster presentation), MISMS Oceania Regional Meeting and Workshop, 15-19 March 2010, Melbourne. Melbourne, National Institutes of Health, 2010.

Researcher : Chong WP

List of Research Outputs

Chong W.P., Zhou J., Law H.K.W., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells., European Journal of Immunology.. 2010, 40: 1718-1727.

Chong W.P., Zhou J., Law H.K., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells, Eur J Immunol. 2010, 40(6): 1718-27.

Chong W.P., Zhou J., Law H.K.W., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells, European Journal of Immunology. 2010, 40: 1-10.

Researcher : Chow PC

List of Research Outputs

Lun K.S., Fan K., Wong C.F., Yung T.C., Chow P.C., Wong K.T., Cheung Y.F., Chow W.H., Chau A.K.T., Chiu S.W. and Cheng L.C., Outcome of thoracic organ transplantation for adults with congenital heart disease, 18^th Annual Scientific Congress, Hong Kong College of Cardiology, Hong Kong, 14-16 May 2010.

Researcher : Chu VLY

List of Research Outputs

Lam S.S., Li L., Chu V.L.Y. and Wong V.C.N., Pilot project of integratin of Chinese medicine (acupuncture) and western medicine for neurohabilitation of children with acquired brain injury - a study of 2 cases, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Wong V.C.N. and Chu V.L.Y., Autism spectrum disorder and traditional Chinese medicine (acupuncture). , In: In: Garralda E, & Raynaud, J-P. (Eds.), ed. , Increasing awareness of child and adolescent mental health. New York: Jason Aronson; 2010.. 2010.

Wong V.C.N., Li L., Lam S.S., Wong C.L. and Chu V.L.Y., Pilot project of integration of Chinese medicine (acupuncture) and western medicine for neurohabilitation of children with acquired brain injury - a study of 2 cases, 19th World Congress of Neurology, Bangkok, Thailand, 24-30 October 2009.

Wong V.C.N. and Chu V.L.Y., Role of Complementary & Alternative Medicine (CAM) Using Acupuncture for Autism Spectrum Disorder (ASD) (poster presentation) , International Meeting for Autism Research, IMFAR meeting, Philadelphia, USA, May 20-22, 2010.

Researcher : Chung BHY

Project Title:	Genetic studies on a multiplex Autism family in Hong Kong
Investigator(s):	Chung BHY, Yang W, Fung CW, Wong VCN
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	01/2009

Abstract:

Autism is the most common neuro-developmental disorder and classically consists of the triad of impairments in social interaction, communication and repetitive stereotypic behaviors. It is heterogeneous and there is a continuum of related disorders, i.e. Autism Spectrum Disorders (ASD). It is estimated to affect 15-20 in 10,000 children, while all ASDs combined affect about 60 in 10,000 children. Study in Hong Kong showed that it has a prevalence of 16.1 per 10,000 children under 15 years old [1]. Autism is a disease with strong genetic component. Twin studies show a concordance of 60-92% for monozygotic twins and 0-10% for dizygotic pairs, depending on phenotypic definitions [2-4]. Despite a strong genetic load, the search for mutations and susceptibility genes for autism has generated mixed and sometimes controversial results. This could be caused by two reasons: one is that the disease may be caused by a combination of many common genetic variations and each with a small contribution to the disease susceptibility, or rare mutations with high penetrance but affecting only small number of families. Secondly, there is probably a strong phenotypic heterogeneity for the disease that confounds the effort in finding the genetic factors involved in the disease. Subpopulation stratification and the possibility that certain genes affecting the disease etiology in one population but not the other could also affect study results. To overcome these obstacles, dramatically increased sample size in an association study or a linkage study using affected sibpairs is essential, although it is often difficult to do. Alternatively, single families of big enough size with multiple affected individuals can be used for linkage studies, thus drastically reduce the possibility of both genetic and phenotypic heterogeneity. For example, it has been reported that a 2-base-pair in Neuroligin 4 gene (NLGN4) in Xp22.33 is responsible for X-linked mental retardation and autism[5], demonstrating the possibility that a complex disease like Autism could be caused by high penetrating mutations in certain families. We have identified a family with 4 affected individuals in Hong Kong that showed a strong indication in both disease homogeneity and involvement of a strong shared genetic factor(s) involved. All the 4 patients are boys and they meet the DSM-IV criteria for autism. Clinical assessment did not reveal any obvious features suggestive of known genetic disorders associated with autism. See attachment for a diagram showing the pedigree and significance of the research proposal References 1. Wong VCN et al. Epidemiological study of autism spectrum disorder in China. J Child Neurol 2008, 23(1): 67-72. 2. Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 2008, 9:341-355. 3. Gupta AR, State MW. Recent advances in the genetics of autism. Biol Psychiatry 2007, 61:429-437. 4. Muhle R et al. The genetics of autism. Pediatrics 2004, 113:e472-486. 5. Laumonnier F, et al. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet 2004, 74:552-557.

Project Title:	30th Annual David W. Smith Workshop on Malformations and Morphogenesis From Heterotaxy to VACTER-H Syndrome - The clinical variability of ZIC3-related disorders
Investigator(s):	Chung BHY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	08/2009
Completion Date:	08/2009

Abstract:

N/A

List of Research Outputs

Andelfinger G., Hitz M.P., Keating S., Mercier J., Teitelbaum R., Richter A., Chung B.H.Y. and Chitayat D., Situs inversus totalis in a fetus with a deletion at 7q36.2 detected on microarray analysis, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Brenner G., Chung B.H.Y., Shannon P., toi A., Shaffer L. and Chitayat D., The first reported case of the DRAGON gene deletion in human. A case with a de-novo interstitial deletion of chromosome 5q15-21.1, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Chitayat D., Chung B.H.Y., Shannon P., Brenner G.J., Toi A. and Shaffer L., The first reported case of the dragon gene deletion in human. A case with a de-novo interstitial deletion of chromosome 5Q15-21.1, David W. Smith 30th Annual Workshop on Malformations and Morphogenesis, The Children's Hospital of Philadelphia, USA, 6-9 August 2009.

Chung B.H.Y., Stavropoulos D.J., Weksberg R. and Yoon G., 2q23.1 microdeletion involving the MBD5 gene - large deletion associated with a relatively mild phenotype, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Chung B.H.Y., Uster-Friedberg T., Pentaz S., Blaser S., Murphy K. and Chitayat D., Enlarged parietal foramina: findings on prenatal ultrasound and mangnetic resonance imaging, Ultrasound in Obstetrics and Gynecology. 2010, 36: 521-524.

Chung B.H.Y., Shaffer L., Keating S. and Chitayat D., From Heterotaxy to VACTERL-H Syndrome - The Clinical Variability of ZiC3-Relatated Disorders, David W. Smith 30th Annual Workshop on Malformations and Morphogenesis, The Children's Hospital of Philadelphia, USA, 6-9 August 2009.

Chung B.H.Y., Genetic and Epigenetic Factors Contributing to Autism Spectrum Disorders, Hong Kong Society of Medical Genetics (Newsletter). 2009, 4: 1-4.

Chung B.H.Y., Genetics of Autism Spectrum Disorders, 13^th Asian Pacific Congress of Pediatrics and 3^rd Asian Congress of Pediatric Nursing, Shanghai, PR China, 14-18 October 2009.

Fernandez B.A., Turner L., MacKay S., Weksberg R., Chung B.H.Y., Roberts W., Vardy C., Whitten K., Marshal C. and Scherer S.W., Dysmorphology assessment on a population basesd cohort of 150 newfoundland children with autism spectrum disorder, David W. Smith 30th Annual Workshop on Malformations and Morphogenesis, The Children's Hospital of Philadelphia, USA, 6-9 August 2009.

Fernandez B.A., Roberts W., Chung B.H.Y., Weksberg R., Meyn S., Szatmari P., Joseph-George A.M., MacKay S., Whitten K., Noble B., Vardy C., Crosbie V., Luscombe S., Tucker E., Turner L., Marshall C.R. and Scherer S.W., Phenotypic Spectrum Associated with De Novo and Inherited Deletions and Duplications at 16p11.2 in Individuals Ascertained for Diagnosis of Autism Spectrum Disorder, Journal of Medical Genetics. 2010, 47: 195-203.

Forrest C., Chung B.H.Y., Silver R., Toi A., Blaser S., Taylor G., Viero S. and Chitayat D., Prenatal diagnosis of scalp congenital hemangiopericytoma, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Fung C.W., Chung B.H.Y., Ng P., Zhao M., Yang W. and Wong V.C.N., Infantile Convulsion Choreoathetosis Syndrome in a Hong Kong Chinese Family, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Hinek A., Chung B.H.Y., Shannon P., Teitelbaum R. and Chitayat D., Restrictive dermopathy with massive thrombosis - a previously uncreognized finding, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Keating S., Chung B.H.Y., Shaffer L. and Chitayat D., From Heterotaxy to VACTER-H syndrome: The clinical variability of ZIC3-related disorders, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Lee P.P.W., Chung B.H.Y., Chan S.Y. and Lau Y.L., Teaching and Learning Medical Genetics - An Interactive Genetics Workshop for Paediatric Clerkship Students, First Runner-up,, Best Poster Presentation: 7^th Asia Pacific Medical Education Conference (APMEC): Excellence in Medical Education - Quality in Healthcare (Trends, Issues, Priorities, Strategies), Medical Education Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 4-8 Februray 2010.

Lee P.P.W., Chung B.H.Y., Chan S.Y. and Lau Y.L., Teaching and Learning Medical Genetics - An Interactive Workshop for Undergraduate Medical Students, 7th Asia Pacific Medical Education Conference, Runner up Poster presenter. 2010.

Lehman A.M., Eydoux P., Doherty D., Glass I.A., Chitayat D., Chung B.H.Y., Langlois S., Yong S.L., Lowry R.B., Hildebrandt F. and Trnka P., Co-Occurrence of Joubert Syndrome and Jeune Asphyxiating Thoracic Dystrophy, American Journal of Medical Genetics (Part A). 2010, 152A: 1411-1419.

Pinto D., Pagnamenta A.T., Klei L., Anney R., Merico D., Regan R., Conroy J., Magalhaes T.R., Correia C., Abrahams B.S., Almeida J., Bacchelli E., Badeer G.D., Bailey A.J., Baird G., Battaglia A., Berney T., Bolshakova N., Bolte S., Bolton P.F., Bourgeron T., Brennan S., Brian J., Bryson S.E., Carson A.R., Casallo G., Casey J., Chung B.H.Y., Cochrane L., Corsello C., Crawford E.L., Crossett A., Cytrynbaum C., Dawson G., de Jonge M., Delorme R., Drmic I., Duketis E., Duque F., Estes A., Farrar P., Fernandez B.A., Folstein S.E., Fombonne E., Freitag C.M., Gilbert J., Gillberg C., Glessner J.T., Goldberg J., Green A., Green J., Guter S.J., Hakonarson H., Heron E.A., Hill M., Holt R., Howe J.L., Hughes G., Hus V., Igliozzi R., Kim C., Klauck S.M., Kolevzon A., Korvatska O., Kustanovich V., Lajonchere C.M., Lamb J.A., Laskawiec M., Leboyer M., Le Couteur A., Leventhal B.L., Lionel A.C., Liu X.Q., Lord C., Lotspeich L., Lund S.C., Maestrini E., Mahoney W., Mantoulan C., Marshall C.R., McConachie H., McDougle C.J., McGrath J., McMahon W.M., Merikangas A., Migita O., Minshew N.J., Mirza G.K., Munson J., Nelson S.F., Noakes C., Noor A., Nygren G., Oliveira G., Papanikolaou K., Parr J.R., Parrini B., Paton T. and Pickles A., Functional impact of global rare copy number variation in autism spectrum disorders, Nature (doi:10.1038/nature09146). 2010, 466: 368-372.

Researcher : Fang JW

List of Research Outputs

Au K.Y., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV TAT modulation of IFN-g induced expression of autophagy-associated genes in primary human blood macrophages., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV Tat modulation of IFN- γ-induction of autophagy-associated genes in primary human blood macrophages., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. December 2-3. 2009.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV Tat modulation of IFN-γ-induced expression of autophagy-associated genes in primary human blood macrophages., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-095]. 2009.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., Travel Award, 2010 Annual General Meeting and Scientific Meeting, Hong Kong Society for Immunology, Hong Kong, April 17, 2010 . 2010.

Fang J.W., Yim H.C.H. and Lau A.S.Y., Interleukin-17A differentially modulates mycobacterial-induction of cytokines in human blood macrophage., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Fang J.W., Li C.B., Yim H.C.H. and Lau A.S.Y., Modulation of mycobacterium bovis (BCG)-induced cytokine response by IL-17., 9th World Congress on Inflammation 2009, Tokyo, Japan, July 8,. 2009.

Lin S.S., Lee D.C.W., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., A role for protein kinase PKR in the medication of Epstien-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression., Cytokine. 2010, 50(2): 210-9.

Lin S.S., Lee D.C.W., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., Best Poster Presentation Award, 2010 Annual General Meeting and Scientific Meeting, Society for Immunology, Hong Kong, April 17, 2010. 2010.

Researcher : Fok SFS

List of Research Outputs

Lee P.P.W., Chen T.X., Jiang L.P., Chan K.W., Yang W., Lee B.W., Chiang W.C., Chen X.Y., Fok S.F.S., Lee T.L., Ho M.H.K., Yang X.Q. and Lau Y.L., Clinical Characteristics and Genotype-phenotype Correlation in 62 patients with X-linked Agammaglobulinemia, Journal of Clinical Immunology. 2010, 30: 121-131.

Researcher : Fung CW

List of Research Outputs

Chan S.H.S., Fung C.W., Yung A.W.Y., Lee S.L., Wong V.C.N., Dale R.C. and Vincent A.C., Anti-NMDA-R encephalitis - an encephalitis lerthargica-like illness, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Chan S.H.S., Wong V.C.N., Fung C.W., Dale R.C., Vincent A., Yung A.W.Y. and Lee S.L., Anti-NMDAR encephalitis - An encephalitis lethargica like illness, 11^th International Child Neurology Congress, Cairo, Egypt, 2-7 May 2010. The International Journal of Child Neuropsychiatry (poster presentaion). 2010, 184.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Siu S., Mak C.M., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitter assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD)(Diamond Prize). 2010.

Fung C.W., Siu S., Blau N., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November, 2009.. 2009.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Blau N., Siu S., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Fung C.W., Chung B.H.Y., Ng P., Zhao M., Yang W. and Wong V.C.N., Infantile Convulsion Choreoathetosis Syndrome in a Hong Kong Chinese Family, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S., Siu S. and Wong V.C.N., Spectrum of mitochondrial diseases in a tertiary referral centre in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Researcher : Fung KL

List of Research Outputs

Chan G.C.F., Fung K.L. and Liang R.H.S., Vincristine but not imatinib could suppress mesenchymal niche’s support to acute lymphoid leukemic (ALL) cells., 41th Congress of the International Society of Paediatric Oncology, Sao Paulo, Brazil, 5 – 9 October 2009.. 2009.

Fung K.L., Liang R.H.S. and Chan G.C.F., Vincristine But Not Imatinib Could Suppress Mesenchymal Niche’s Support to Lymphoid Leukemic Cells, Leukemia Lymphoma. 2010, 51(3): 515-522.

Researcher : Guan J

List of Research Outputs

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Researcher : Ha SY

List of Research Outputs

Chan G.C.F., Shing M.M.K., Luk C.W., Li R.C.H., Ling S.C., Li C.K. and Ha S.Y., Characteristics and outcome of metastatic infant neuroblastoma. (oral presentation), Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association Ltd. 28 November . 2009.

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (Deferoxamine, deferiprone and deferasirox) on the growth of klebsiella pneumoniae and aeromonas hydrophila isolated from transfusion-dependent thalassaemia patients., Hemoglobin (Proceedings of the 17th International Conference on Chelation (ICOC), Shenzhen, PR China 23-27 November 2007). 2009, 33(5): 352-360.

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (Desferal, Deferiprone & Deferaairox) on the growth of klebsiella and aeromonas isolated from transfusion dependent thalassaemia patients., Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association Ltd. 28 November. 2009.

Chan G.C.F., Chan S., Ho P.L. and Ha S.Y., Effects of chelators (desferal, deferiprone & deferasirox) on the growth of Klebsiella and Aeromonas isolated from transfusion dependent thalassemia patients., Hemoglobin. 2009, 33(5): 352-360.

Chan G.C.F., Shing M.M.K., Yuen H.L., Lee A.C.W., Li C.K., Luk C.W., Ha S.Y. and Li C.K., Epidemiology & treatment outcome of childhood ependymoma in Hong Kong: Report from the Hong Kong Pediatric Hematology Oncology Study Group., Joint Annual Scientific meeting of the Hong Kong Paediatric Society & Hong Kong Paediatric Nurses Association Ltd. Nov 13, . 2009.

Chan G.C.F., Shing M.M.K., Luk C.W., Lee A.C.W., Ling A.S.C., Li C.K. and Ha S.Y., Treatment outcome of metastatic neuroblastoma with antiganglioside 2 monoclonal antibody (3F8): The Hong Kong experience., 41th Congress of the International Society of Paediatric Oncology, Sao Paulo, Brazil, 5 – 9 October 2009. (Award Presentation Session). 2009.

Cheuk D.K.L., Chiang A.K.S., Chan G.C.F. and Ha S.Y., Urate oxidase for the prevention and treatment of tumor lysis syndrome in children with cancer, Cochrane Database Syst Rev. 2010;6:CD006945. 2010, 6: 1-48.

Cheung J., Au W.Y., Ha S.Y., Jensen J., Kim D., Ding A., Zhou I., Guo H., Brown T., Chu W., Rasalkar D. and Khong P.L., Monitoring iron chelation effect in hearts of thalassaemia patients with improved sensitivity using reduced transverse relaxation rate (RR2), Joint ISMRM-ESMRMB Annual Scientific Meeting, Stockholm, Sweden, 1-7 May 2010.

Cheung Y.F., Hong W., Chan G.C.F., Wong S.J. and Ha S.Y., Left ventricular myocardial deformation and mechanical dyssychrony in chidlren with normal ventricular shortening fraction after anthracyline therapy , The 6th Korea-Japan-China Pediatric Heart Forum, March 26-27, Seoul, Korea. 2010.

Cheung Y.F., Liang X., Chan G.C.F., Wong S.J. and Ha S.Y., Myocardial deformation in patients with beta-thalassemia major: a speckle tracking echocardiographic study , Echocardiography. 2010, 27: 253-259.

Guo H., Au W.Y., Cheung J.S., Kim D., Jensen J.H., Khong P.L., Chan Q., Chan K.C., Tosti C., Tang H., Brown T.R., Lam W.W.M., Ha S.Y., Brittenham G.M. and Wu E.X., Myocardial T2 quantitation in patients with iron overload at 3 tesla, Journal of Magnetic Resonance Imaging . 2009, 30: 394-400.

Ha S.Y., Mok S.P., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*. , Hemoglobin. 2009, 33(5): 323-331.

Ha S.Y., Mok S.P., Chu W.C.W., Rasalkar D.D., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*., Hemoglobin (Proceedings of the 17th International Conference on Chelation (ICOC), Shenzhen, PR China 23-27 November 2007).. 2009, 33(5): 323-331.

Qiu D., Chan G.C.F., Chan Q., Ha S.Y. and Khong P.L., Susceptibility weighted imaging (SWI) for the assessment of iron loading in the brain of beta-thalassemia major patients., 1st meeting of the Asia-Pacific Iron Academy, Chiang Mai, 23-26 Nov 2009.

Qiu D., Chan G.C., Chan Q., Ha S.Y. and Khong P.L., Susceptibility weighted imaging (SWI) for the assessment of iron loading in the brain of beta-thalassemia major patients, Joint ISMRM-ESMRMB Annual Scientific Meeting, Stockholm, Sweden, 1-7 May 2010.

Researcher : Ho DNY

Project Title:	Mechanisms of Epstein-Barr Virus (EBV) microRNAs in maintaining viral latency
Investigator(s):	Ho DNY, Chiang AKS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	12/2009

Abstract:

Background: Epstein Barr virus (EBV) is a ubiquitous human oncogenic herpesvirus, which its infection of the host cells exists in two forms, namely the latent and lytic forms. Generally, latently infected individuals are asymptomatic. However, in certain cases, the virus is implicated in the development of malignancies including Burkitt’s lymphoma (BL), nasopharyngeal carcinoma (NPC), gastric carcinoma (GC) and Hodgkin’s diseases (HD). In latency state, EBV only expressed a handful of viral genes, which consists of nine latent proteins, two polyadenylated viral RNAs EBERs and a number of non-coding miRNAs. Intermittently, these EBV carriers will enter the lytic cycle, which trigger viral replication, production of lytic proteins, followed by lysis of the hosts and finally release of virions to infect neighboring cells [1]. Over the years, despite much effort has been put into the study of EBV reactivation, a comprehensive model with detailed mechanisms on virus induction is still lacking. However, the recent discovery of EBV miRNAs might change this situation. It has opened up an entire new direction on explaining how EBV might utilize these latently encoded RNA to control the switching between its latent and lytic cycle. Our major goal is to understand the possible role of EBV miRNAs in maintaining the virus latency, trying to identify the pathways involved and hence come up with a rationalization of how EBV might contribute to the development of cancers. MicroRNAs (miRNA) are short (~22-nucleotides), endogenous, non-coding RNA molecules that play an important role in regulating gene expressions. To date, thousands of miRNAs have been identified for human, animals, plants and viruses, which sequences are available in the miRBase Registry (http://microrna.sanger.ac.uk/). These ribonucleotides recognize their target mRNAs by complementary base pairing with the 3’UTR (untranslated regions) to promote translational repression or mRNA degradation [2]. EBV encodes a total of 25 pre-miRNAs, clustered into two regions, termed miR-BHRF1-1-3 and miR-BART1-22 [3]. Reasoned from their known targets, EBV miRNAs bear at least three possible functions. First, they serve as a viral anti-apoptosis agent to promote host cell survival. This is implied by the findings that overexpression of BART miRNAs can suppress the production of EBV encoded LMP1, an apoptotic stimuli [4], and miR-BART5 downregulate cellular protein PUMA, a p53 up-regulated modulator of apoptosis [5]. Second, these viral miRNAs are demonstrated to be part of the virus effort in evading the host immune system, suggested by the study that miR-BHRF1-3 reduces the expression of CXCL-11/I-TAC, an IFN inducible T-cell attracting chemokine [6]. Similarly, miR-BART2-5p also inhibits the stressed-induced immune molecule MICB to avoid NK cell killing [7]. Third, the EBV miRNA miR-BART2 involved in delaying the lytic cycle by decreasing the abundance of viral DNA polymerase gene BALF5 [8]. Overall, these functions point to the fact that EBV miRNAs play a central role in maintaining the virus latency. To trigger the reactivation of EBV lytic cycle, a number of physiological stimuli and their corresponding pathways have been identified. This includes antigen stimulation of B-cell receptor (BCR) related signaling pathways, TGF-beta induction via the ERK cascade and phobol esters activation of protein kinase C. The lytic gene expressions then proceed in a sequential order, the immediate early (IE) genes followed by early and late genes [9]. If EBV miRNAs actually play a role in establishing latency and subsequently delaying reactivation of the latent virus, it would be obvious that they will target either the viral IE genes or the cellular factors that governed IE gene productions. Therefore, it is critical to understand the relationships between EBV miRNAs and viral genes’ expressions during early stage of induction. These findings should lead to a better picture on detailed mechanisms characterizing the reactivation of EBV from latent to lytic states. Project objectives: 1. Identify EBV miRNAs that inhibit or delay the reactivation of virus lytic cycle: Using bioinformatics to predict miRNAs potentially target IE genes BZLF1 and BRLF1. Expression pattern of the miRNAs are compared between latent and lytic state using northern blot and qPCR methods to pick out potential candidates. 2. Confirm that the miRNA candidates are capable to suppress EBV reactivation: Overexpression and knockdown of the identified viral miRNAs, then observe the expression levels of immediate-early and early lytic proteins 3. Determine the possible mechanisms of EBV miRNAs in maintaining viral latency: Verification of miRNA-IE genes interactions using luciferase reporter assay. Investigate whether the selected miRNAs are capable to delay or even abolish the viral lytic cycle by varying the amount of stimuli and monitor the IE genes expressions in different timepoints. References 1. Rickinson, A.B. and E. Kieff. Epstein-Barr Virus, in Fields Virology. p. 2656-2700. 2. Bartel, D.P. (2009) MicroRNAs: Target Recognition and Regulatory Functions. Cell. 136(2): p. 215-233. 3. Cai, X., et al. (2006) Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog. 2(3): p. e23. 4. Lo, A.K., et al. (2007) Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc Natl Acad Sci U S A. 104(41): p. 16164-9. 5. Choy, E.Y.-W., et al. (2008) An Epstein-Barr virus-encoded microRNA targets PUMA to promote host cell survival. J. Exp. Med. 205(11): p. 2551-2560. 6. Xia, T., et al. (2008) EBV MicroRNAs in Primary Lymphomas and Targeting of CXCL-11 by ebv-mir-BHRF1-3. Cancer Res. 68(5): p. 1436-1442. 7. Nachmani, D., et al. (2009) Diverse Herpesvirus MicroRNAs Target the Stress-Induced Immune Ligand MICB to Escape Recognition by Natural Killer Cells. Cell Host Microbe. 5(4): p. 376-385. 8. Barth, S., et al.. (2008) Epstein-Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5. Nucleic Acids Res. 36(2): p. 666-75. 9. Amon, W., and P.J. Farrell. (2005) Reactivation of Epstein-Barr virus from latency. Rev. Med. Virol. 15(3):p. 149-56.

Researcher : Ho MHK

List of Research Outputs

Ha S.Y., Mok S.P., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*. , Hemoglobin. 2009, 33(5): 323-331.

Ha S.Y., Mok S.P., Chu W.C.W., Rasalkar D.D., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*., Hemoglobin (Proceedings of the 17th International Conference on Chelation (ICOC), Shenzhen, PR China 23-27 November 2007).. 2009, 33(5): 323-331.

Ho M.H.K., Lee S.B.H., Wong W.H.S. and Lau Y.L., Peanut oil and peanut allergy, foes or folks?, Archives of Disease in Childhood [Epub in print]. 2010, 1-2.

Lee P.P.W., Chen T.X., Jiang L.P., Chan K.W., Yang W., Lee B.W., Chiang W.C., Chen X.Y., Fok S.F.S., Lee T.L., Ho M.H.K., Yang X.Q. and Lau Y.L., Clinical Characteristics and Genotype-phenotype Correlation in 62 patients with X-linked Agammaglobulinemia, Journal of Clinical Immunology. 2010, 30: 121-131.

Lee P.P.W., Lee T.L., Ho M.H.K., Zeng H.S., Chen X.Y., Chan K.W., Tu W. and Lau Y.L., Invasive Penicillium marneffel Infection in Children without Acquired Immunodeficiency Syndrome (AIDS) - An Indicator Disease for Primary Immunodeficiency?, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W., Chan K.W., Chen T.X., Jiang L.P., Wang X.C., Zeng H.S., Chen X.Y., Lee B.W., Shek L., Liew W.K., Lee C.W., Yu H.H., Latiff Z.A., Ho M.H.K., Lee T.L. and Lau Y.L., Molecular diagnosis of severe combined immunodeficiency - Identification of IL2RG, JAK3, IL7R, DCLRE1C and RAG2 mutations in a cohort of Chinese and Southeast Asian children, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W., Lau Y.L., Ho M.H.K., Lee T.L. and Chan K.W., Primary Immunodeficiency Referral Network in Asia: Database Review 2001 – 2009, Young Investigator Award, 6th Congress of Asian Society for Pediatric Research . 2010.

Lee P.P.W., Chan K.W., Wong W.H.S., Ho M.H.K., Lee T.L. and Lau Y.L., Primary Immunodeficiency Referral Network in Asia: Database Review 2001-2009, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Yang W., Shen N., Ye D.Q., Liu Q., Qian X.X., Hirankarn N., Pan H.F., Mok C.C., Chan D.T.M., Wong R.W.S., Lee K.W., Wong S.N., Leung A.M.H., Li X.P., Avihingsanon Y., Wong C.M., Lee T.L., Ho M.H.K., Lee P.P.W., Chang Y.K., Li P.H., Li R., Zhang L., Wong W.H.S., Ng I.O.L., Lau W.C.S., Sham P.C., Lau Y.L. and Asian Lupus Genetics Consortium A.L.G.C., Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. , PLoS Genetics. 2010, 6: e1000841.

Researcher : Hong W

List of Research Outputs

Cheung Y.F., Hong W., Chan G.C.F., Wong S.J. and Ha S.Y., Left ventricular myocardial deformation and mechanical dyssychrony in chidlren with normal ventricular shortening fraction after anthracyline therapy , The 6th Korea-Japan-China Pediatric Heart Forum, March 26-27, Seoul, Korea. 2010.

Hong W., Yung T.C., Lun K.S., Wong S.J. and Cheung Y.F., Impact of right ventricular pacing on three-dimensional global left ventricular dyssynchrony in children and young adults with congenital and acquired heart block associated with congenital heart disease , The American Journal of Cardiology. 2009, 104: 700-706.

Hong W., Yung T.C., Lun K.S., Wong S.J. and Cheung Y.F., Impact of temporary interruption of right ventricular pacing for heart block on left ventricular function and dyssynchrony. , Pacing and Clinical Electrophysiology. 2010, 33: 41-48.

Researcher : Huen KF

List of Research Outputs

Huen K.F., Low L.C.K., Cheung P.T., Wong G.W.K., But B.W.M., Kwan E.Y.W., Lam Y.Y., Lee C.Y., Wong L.M., Ng K.L., Cheng A.W.F., Tong C.T. and Wong W.H.S., An Update on the Epidemiology of Childhood Diabetes in Hong Kong , Hong Kong Journal of Paediatrics . 2009, 14: 252-259.

Researcher : Hui KF

List of Research Outputs

Hui K.F. and Chiang A.K.S., Suberoylanilide hydroxamic acid (SAHA) induces viral lytic cycle in Epstein-Barr Virus-positive epithelial malignancies and mediates enhanced cell death, 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong, 2-3 December. 2009.

Hui K.F. and Chiang A.K.S., Suberoylanilide hydroxamic acid (SAHA) induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death, 6th Hong Kong International Cancer Congress, LKS Faculty of Medicine, The University of Hong Kong, 4-6 November. 2009.

Hui K.F., Tsao G.S.W. and Chiang A.K.S., Suberoylanilide hydroxamic acid induces Epstein-Barr virus lytic cycle and enhanced apoptosis in nasopharyngeal carcinoma, 101st Annual Meeting of American Association for Cancer Research, Washington, DC, USA, 17-21 April. 2010.

Hui K.F. and Chiang A.K.S., Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death., International Journal of Cancer 126:2479-2489. 2010.

Researcher : Ip P

Project Title:	Early Detoxification of Substance Abusing Mothers improves developmental and behavioural outcome of their children
Investigator(s):	Ip P, Chan EKL
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2010

Abstract:

Children born to substance abusing women face many risks that can impede optimal developmental outcome. These risks include both potential neurologic and organic sequelae of intrauterine substance exposure, as well as additional risk factors in their postnatal environment (Wallace & Belcher, 1998). They are vulnerable to a wide range of physical, developmental and behavioral problems (Webster, Reid & Hammond, 2001; Roberts, 1999; Josephine, 2003). With the accumulative experience of Head Start and other early childhood intervention programs worldwide, children of underprivileged families are found to be adversely influenced by early life environment, and they are more likely to start at a much disadvantaged position than their counterparts (Garces, Thomas & Currie, 2002). Comprehensive Child Development Service (CCDS), a community-based early childhood intervention program targeted at high-risk families, has been implemented in different districts of Hong Kong in stepwise fashion since 2006 (Leung, Chan, Lee & Ip, 2007). Under this new integrated service, young children born to mothers with substance abuse were identified during their pregnancy or early infancy and followed up longitudinally in the first five years of life. They are found to be at risk of developmental delay, behavioural problems and child abuse (Ip, Chan, Lee & Chow, 2008). There is an obvious need to tackle this important issue in order to optimize the potential of this group of children at-risk and provide them an equal starting point as other children. Modification of the most important risk factors, i.e. early detoxification of their mothers and early school placement to tackle against the environmental understimulation, have been observed clinically to be an important strategy to improve their outcome but there have been lack of scientific research in this important issue in Hong Kong and the rest of China. Hypothesis: Early Detoxification of Substance Abused Mothers improves their children’s developmental and behavioural outcome and reduces the risk of child abuse. Objectives: 1) To study differences in developmental profiles of children of substance abused mothers between those with mothers received early detoxification and those with mothers who continued substance abuse. 2) To study differences in behaviours of children of substance abused mothers between those with mothers received early detoxification and those with mothers who continued substance abuse. 3) To study differences in the risk of child abuse of children of substance abused mothers between those with mothers received early detoxification and those with mothers who continued substance abuse. Key Issues – International Level Importance of Early Childhood and Environmental Effects - Early life experience are built into our body and all these adversities would become early childhood roots of impairments in health, learning and behavior (Shonkoff, Boyce & McEwen, 2009). Emerging research in early child development documents the rapid brain development in the first years of life and the positive influence of environmental stimulation (Shonkoff & Phillips, 2000). Further research has drawn attention to the larger economic returns of government investment in early childhood compared with adulthood (Heckman, 2004). These findings have led countries in North America, Europe and Australia to accord increased importance to early childhood education. Substance Abuse and its trend – Substance misuse has increased dramatically in young people in the past one to two decades, in part because of a worldwide pro-drug youth culture (Kumpfer, Alvarado & Whiteside, 2003). Despite more than a decade of reductions in drug use, 30-day marijuana use among adolescents in the United States increased 99% (11.9% to 23.7%) among 12th graders and 154% (8.1% to 20.5%) in 10th graders in the United States within only five years between 1992 and 1997 (Johnston et al., 2001). Similarly, there have been a general rising trend in abusing psychotropic substance from 1997-2006 in Hong Kong, where the number of psychotropic substance abusers reached a record high at 7364 in 2006. Number of substance abusers among teenagers less than 21 increased by 40% in 2005-2007 and then increased by another 20% in 2007-2008 (CRDA, H.K., 2009). Problems being addressed Vulnerable Children of Drug Abusing Mothers – Children born to substance abusing women face many risks that can impede optimal developmental outcome. These risks include both potential neurologic and organic sequelae of intrauterine substance exposure, as well as additional risk factors in their postnatal environment (Wallace & Belcher, 1998). They are vulnerable to a wide range of physical, developmental and behavioral problems (Webster, Reid & Hammond, 2001; Roberts, 1999; Josephine, 2003). With the accumulative experience of Head Start and other early childhood intervention programs worldwide, children of underprivileged families are found to be adversely influenced by early life environment, and they are more likely to start at a much disadvantaged position than their counterparts (Garces, Thomas & Currie, 2002). Both overseas and local experience suggests the vulnerability of children born to substance abusing mothers to developmental delay, behavioural problems, child abuse and neglect. Modification of Risk Factors in Early Childhood Environment – As children of substance abusing mothers have been adversely influenced by early risky environment with exposure to substance abusing behaviour of adults, understimulation and neglect, modification of the early life environment seems to be a logical approach in tackling this important issue. Early detoxification of substance abused mothers has been observed to be an effective strategy in improving parenting and enhancing family bonding in a local early intervention program. In addition, children at risk of developmental delay seems to benefit from early schooling environment which serves as a protective factor against the early environment of understimulation. Hence specific strategy to achieve successful early detoxification of substance abused mothers and arrangement of early school placement is probably useful in improving their children’s outcome.

List of Research Outputs

Ip P., A better look at learning: how does the brain express the mind? , Archives of Disease in Childhood. 2010.

Ip P., BB發燒點算好？找出原因防併發症。明報 (Ming Pao Daily News) 。 2010年３月３０日 , 2010.

Ip P., Child Abuse and Poverty in Hong Kong - Impact on Child Health , Symposium on Community Child Health, Hong Kong . 2010.

Ip P., Child Health Survey - The First Population Health Survey Targeted to Children in Hong Kong, 8th Guangdong-Hong Kong and 2nd Hong Kong-Guangdong-Shanghai-Chongqing Paediatric Exchange Meeting, 26 June 2010. 2010.

Ip P., High-risk pregnancy and early brain development , Postgraduate Seminar, Hong Kong College of Obstetricians & Gynaecologists. 2010.

Ip P., Ming Pao Interview, Happy Pa Ma session on "發燒抽筋6歲前小心 (1 - 2歲)". 3 January 2010., 2010.

Ip P., Reviewer, Archives of Disease in Childhood, 2010, 2010.

Ip P., Reviewer, Journal of Neurology, Neurosurgery & Psychiatry. 2010.

Ip P., “校園禁毒錦囊-快速識別篇之毒品對健康的傷害”(pg 21-24), HKU Space & S.A.R.D.A Publishing., March 2010., 2010.

Ip P., 東方日報「醫健寶庫」系列: 三歲定八十, 七歲看終身 - 童年陰影勿輕視 (Early child adversity 1), 14 March 2010. , 2010.

Ip P., 東方日報「醫健寶庫」系列: 幼兒有壓力, 家人助解決 - 家人支持有助兒童減壓 (Early child adversity 2), 21 March 2010, 2010.

Ip P., 媽媽濫藥對胎兒及初生嬰兒的影響, 成長希望基金會香港戒毒會合辦, 濫藥婦女育兒教材簡介會, 2010.

Ip P., “濫藥孕婦，毒害胎兒”。東方日報 (Oriental Daily News) 。 2010年2月7日, 2010.

Ip P., “戒毒會推教材，助濫藥母育兒”。明報 (Ming Pao Daily News) 。 2010年2月7日, 2010.

Ip P., “孕婦濫藥誕弱智畸嬰” 。太陽報 (The Sun) 。 2010年2月7日, 2010.

Ip P., “吸毒孕婦，誤信索K無損胎兒”。文匯報 (Wen Wei Po) 。 2010年2月7日, 2010.

Siu B.W.M., Ip P., Chow H.M.T., Kwok S.S.P., Li O.L., Cheung E.F.C., Yeung T.M.H. and Hung S.F., Impairment of mother-infant relationship: validation of the Chinese version of postpartum bonding questionnaire, Journal of Nervous and Mental Disease . 2010, 198: 174-179.

Researcher : Ko LY

List of Research Outputs

Ko L.Y., Chau A.K.T., Yung T.C., Cheung Y.F. and Lun K.S., Retrospective Review on Anomalous Left Coronary Artery from Pulmonary Artery , Hong Kong Journal of Paediatrics . 2010, 15: 12-18.

Researcher : Kwan EYW

List of Research Outputs

Huen K.F., Low L.C.K., Cheung P.T., Wong G.W.K., But B.W.M., Kwan E.Y.W., Lam Y.Y., Lee C.Y., Wong L.M., Ng K.L., Cheng A.W.F., Tong C.T. and Wong W.H.S., An Update on the Epidemiology of Childhood Diabetes in Hong Kong , Hong Kong Journal of Paediatrics . 2009, 14: 252-259.

Researcher : Kwan QKL

List of Research Outputs

Wong V.C.N. and Kwan Q.K.L., Randomized Controlled Trial for Early Intervention for Autism: A Pilot Study of the Autism 1-2-3 Project, Journal of Autism & Developmental Disorders. 2010, 40(6): 677-688.

Researcher : Kwok AMK

List of Research Outputs

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Siu S., Mak C.M., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitter assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD)(Diamond Prize). 2010.

Fung C.W., Siu S., Blau N., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November, 2009.. 2009.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Blau N., Siu S., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S., Siu S. and Wong V.C.N., Spectrum of mitochondrial diseases in a tertiary referral centre in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Poon G.W.K., Kwok A.M.K., Cheung P.T., Yung T.C., Ng Y.K., Tsoi N.S., Wong K.Y. and Low L.C.K., Variable Response to Enzyme Replacement Therapy in Two Chinese Children with Infantile-onset Pompe Disease in Hong Kong , Hong Kong Journal of Paediatrics. 2009, 14: 243-251.

Researcher : Lam KT

List of Research Outputs

Mao H., Tu W., Qin G., Law H.K., Sia S.F., Chan P.L., Liu Y., Lam K.T., Zheng J., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, J Virol. 2009, 83(18): 9215-22.

Mao H., Tu W., Qin G., Lau H.K.W., Chan P.L., Liu Y., Lam K.T., Zhang Y., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, Journal of Virology. 2009, 83: 9215-9222.

Mao H., Tu W., Liu Y., Qin G., Zheng J., Chan P.L., Lam K.T., Peiris J.S.M. and Lau Y.L., Inhibition of human natural killer cell activity by influenza virions and hemagglutinin, J Virol. 2010, 84(9): 4148-57.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Lam K.T., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses, J Infect Dis. 2009, 200(6): 858-65.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., lewis D.B., Lau Y.L. and Tu W., Efficient Induction and Expansion of Human Alloantigen-Specific CD8 Regulatory T Cells from Naive Precursors by CD40-Activated B Cells. , Journal of Immunology. U.S.A., 2009, 2009 Aug 14.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., Lewis D.B., Lau Y.L. and Tu W., Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells, J Immunol. 2009, 183(6): 3742-50.

Researcher : Lau ASY

Project Title:	Cytokines, Signaling & Diseases 2003 The Role of Protein Kinase PKR in the Induction of Cytokine Expression by Bacillus Calmette Guerin Through NF-kappaB
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2003

Abstract:

N/A

Project Title:	Cytokine Dysregulation and Virus-Induced Cell Death in Avian Influenza Virus Infections
Investigator(s):	Lau ASY, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2005

Abstract:

Objectives: In this project, we will use H9N2 as prototypes to examine the cellular effects of TNF and IFN induction by avian influenza viruses. We will delineate whether there is differential induction of cytotoxicity by the avian viruses from the human ones. We will also examine the consequences of simultaneous induction of TNF and IFN on cell survival and expression of apoptotic genes. Our Specific Aims are 1) We will delineate whether there is a differential induction of cytotoxicity by the avian viruses (H9N2) compared to the human ones (H1N1 or H3N2). 2) We will examine the consequences of simultaneous induction of TNF and IFN on cell survival and expression of apoptotic genes. Background Influenza A virus infects a wide range of species, including poultry, swine, horses, seals and humans. Of the 15 hemagglutinins (HA) subtypes of influenza A, only H1, H2 and H3 had been known to cause significant morbidity and mortality in humans (1-3). The 1997 outbreak of avian influenza H5N1/97 in Hong Kong was the first documented cases of primary pneumonia rapidly progressing to adult respiratory distress syndrome and multiple organ dysfunctions in humans. In light of the high mortality of H5N1/97 infection, it would be desirable to understand the pathogenesis in order to enhance the development of novel therapy. Influenza A viruses are known to replicate in epithelial cells and leukocytes, resulting in induction of cytokines(4). During influenza virus infection, a multiple array of cytokines, including chemokines (Rantes, MIP-1), and interferons (IFN-α and –β), is induced (5,6). The biological actions of IFNs are mediated by multiple pathways resulting in mRNA degradation by ribonuclease L and inhibition of translation by a dsRNA-activated kinase, PKR. PKR is inducible by IFN, TNF-α, and dsRNA [viral RNA analogue] (7,8). We have previously shown that PKR mediates the cytotoxicity of TNF-α in cells of diverse tissue origins including fibroblasts and monocytes (9). It has been proposed that PKR serves as a common pattern-recognition molecule responsible for mediating these virus-induced antiviral effects (8-11). We previously demonstrated PKR serves multiple roles in the cell including the mediation of TNF-induced cytotoxicity, and induction of apoptotic gene p53 and IFN expression (9, 12-16). The signal transduction role of PKR is further confirmed by its effects on the induction of Fas and NF-kB, following TNF-α or endotoxin treatment. TNF-α is a potent, cytotoxic molecule induced in response to invasion by infectious pathogens or cancer cells. Elevated levels of TNF-α in the serum have been correlated to and predictive of morbidity and mortality in patients with meningococcemia. To unravel the pathogenesis of fulminant H5N1/97 disease in humans, we have developed a H5N1/97-blood macrophage (BMac) model to examine the interactions of H5N1/97-encoded genes and cellular factors which may result in immune dysregulation (17: Peiris as PI and Lau as co-I). Using our model, we have previously demonstrated that H5N1/97 induced dramatically higher levels of cytokine expression when compared to those elicited by “conventional” human H1N1 or H3N2 viruses (17). TNF-α protein levels in H5N1/97-infected macrophage culture supernatants were comparable to those induced by stimulation with E. coli endotoxin, and much higher than those in H1N1 or H3N2 infections (17). Recently, we further demonstrated that the TNF induction and its cytotoxicity are mediated, at least in part, by mitogen-activated protein (MAP) kinases including p38 and ERK (18: J Virol 2005, accepted May 2005, Lau as PI). Induction of proinflammatory cytokines is a major defense mechanism of the host to mobilize the immune system and to combat the invading pathogen. We hypothesize the high mortality associated with H5N1/97 infections may be due to an uncontrolled induction of IFN and TNF, consequent to virus interactions with cellular signaling pathways, leading to dysregulated immune response and differential effects on cell death.

Project Title:	HIV dysregulation of the toll-like receptor system - implications for pathogenesis
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2006

Abstract:

To investigate the effects of Tat on the expression of TLR2 in primary blood monocytes and identify whether there are other TLRs inducible by Tat; to identify the kinases and signaling pathways operative in Tat induction of TLR2 and its related receptors; to investigate whether the enhanced TLR plays a role in infection by HSV and the level of viral replication in monocytes; to examine the effects of Tat on astrocytic cells including TLR expression and infection by HSV.

Project Title:	HIV suppression of the interferon-gamma signaling pathway and autophagy: implications for mycobacterial pathogenesis
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2007

Abstract:

To confirm the mechanism of HIV suppression of the IFN-gamma induced signaling system; to examine whether SOCS genes play a role in HIV perturbation of Jak/STAT1 activation; to investigate whether HIV and its proteins suppress IFN-gamma-induced autophagy activities against mycobacteria; to identify potential IFN-gamma-induced autophagy genes that are suppressed by HIV.

Project Title:	Immunomodulatory effects of Panax ginseng on Human Monocytic Cells
Investigator(s):	Lau ASY, Lee DCW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2007

Abstract:

Objectives: In this project, we will perform microarray analysis to investigate the gene expression profile of human monocytic cells after Panax ginseng treatment and the mechanisms of immunomodulatory effects of Panax ginseng on inflammation. Our Specific Aims are: 1) We will investigate the gene expression profile of human monocytic cells with Panax ginseng treatment during inflammation. 2) We will delineate the mechanisms of the immunomodulatory effects of Panax ginseng on inflammation. Background Traditional Chinese Medicine (TCM) has long been recognized as a potential alternative remedy to treat chronic diseases and microbial infections by modulating the host’s immune system (1, 2). Panax ginseng, also known as Asian ginseng, is one of the most commonly used herbal medicines in China, Asia and Western countries (3). Ginseng contains multiple active components with potential beneficial effects on the central nervous system, neuroendocrine function, immune and cardiovascular systems in humans (3, 4). However, the precise actions of ginseng in humans remain to be investigated. Cytokines are potent pleiotropic polypeptides that play critical roles in inflammatory responses and are capable of orchestrating the complicated network of innate and adaptive immune responses following microbial infection. Production of cytokines in the host is tightly regulated by different mechanisms to maintain the immunologic homeostasis. Recent studies including ours have shown that an imbalanced production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF) and interleukin-6 (IL-6), and anti-inflammatory cytokines, including IL-10, is implicated in the pathogenesis of diseases (5, 6, 7, 8). TNF is a major mediator of apoptosis and inflammation and it has been shown to have a pivotal role in the pathogenesis of a wide variety of human diseases. TNF, upon binding to its cognate receptor (TNF receptor-1), recruits several intracellular adaptor proteins including TRADD, TRAF2, RIP, and FADD leading to activation of MAP kinase signaling cascades and their associated transcription factors NF-kB and AP-1(9, 10). Studies of the polysaccharide extracts of ginseng and ginsenosides have shown that ginseng modulates the inflammatory response by enhancing the phagocytic activity of macrophages and blocking the activation of specific transcriptions such as NF-kB and AP-1 (11, 12). The immunomodulatory and anti-inflammatory properties of ginseng have been attributed to its effects in regulating phagocytic activities and cytokine production of immune cells (13, 14, 15, 16). We hypothesize that ginseng modulates the inflammatory responses via regulation of specific signaling kinase activities that lead to cytokine expression in immune cells. In this project, we will confirm our pilot results that ginseng regulates the expression of several proinflammatory cytokines. Further, we will examine the gene expression profile of monocytic cells treated with ginseng and its component molecules, ginsenosides. Reference: 1. Fan TP et al. Trends Pharm Sci 2006; 27: 297-309 2. Tan BK and Vanitha J. Curr Med Chem 2004; 11: 1423-30 3. Gillis CN. Biochemical Pharmacology 1997; 54: 1-8 4. Attele AS et al. Biochemical Pharmacology 1999; 58: 1685-93 5. McInnes IB and Schett G. Nat Rev Immunol 2007; 7: 429-42 6. Lin WW and Karin M. J Clin Invest 2007; 117: 1175-83 7. Lee DCW, Lau AS et al. J Virol 2005; 79: 10147-54. 8. A) Li JCB, Lau AS et al. FEBS Lett 2005; 579: 3055-62. B) Cheung BKW, Lau AS et al. J Immunol. 2005;175:7218-25. 9. Chen G and Goeddel DV. Science. 2002; 296:1634-5 10. Dempsey PW et al. Cytokine Growth Factor Rev. 2003;14: 193-209 11. Ahn JY et al. Eur J Immunol. 2006; 36: 37-45 12. Park SA etal. Ann N Y Acad Sci. 2007; 1095: 545-53. 13. Nakaya TA et al. J Interferon Cytokine Res 2004; 24: 93-100 14. Shin JY et al. Immunopharmacol Immunotoxicol 2002; 24: 469-82 15. Mizuno M et al. Biochem Biophys Res Commun 1994; 200: 1672-8 16. Sonoda Y. Immunopharmacology 1998; 38: 287-94

Project Title:	Roles of Autophagy in Host Immune Response to Influenza Virus Infection
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2008

Abstract:

Following virus infection, host cells mount different antiviral responses to control the invasion, and in extreme cases, death of the infected cells. The cell death processes including apoptosis has been postulated to be one of the effective host defense mechanisms for virus invasion (1). Induction of apoptosis results in inhibition of virus replication, limitation of virus dissemination, and minimization of uncontrolled inflammatory responses. Autophagy is a conserved homeostatic process to serve as a cell survival mechanism during starvation (2). The antiviral role of autophagy is strengthened by the involvement of autophagic process in the induction of type I IFNs in virus infection (3). However, viruses such as coronavirus and poliovirus have evolved strategies to divert autophagy to promote their own replication and survival in the autophagic cells (2,4). It is possible that influenza viruses may evade host immunity via prevention of early cell death. To investigate the mechanisms underlying the diversion of cell death processes, we hypothesize that avian influenza viruses divert the cell death pathways from apoptosis, which ultimately involves whole cell death, to that of autophagy, which is a self-sustained process resulting in removal of unwanted subcellular structures, leading to prolonged survival of the avian virus-infected cells. With longer survival of H5N1-infected cells in autophagy instead of apoptosis, there are opportunities for the completion of virus replication and consequent immune dysregulation. Question I. Since we have documented a delayed apoptosis in primary blood macrophages with H5N1 infection, is there an activation of the autophagy process? What is the process of cell death in avian virus-infected cells, compared to human influenza viruses? Aim 1. To examine whether autophagy is activated in the avian and human influenza viruses infected cells, in addition to apoptosis. Question II. Once autophagy is documented, what are the mechansims utilized by the avian and human influenza viruses? What is/are the functional role(s) of autophagy in host’s immune responses? Aim 2. To investigate the mechanisms underlying the activation of autophagy and the role of autophagy involved in the induction of cytokines.

Project Title:	Factors affecting mycobacteria evasion of immunity: effects of HIV on cellular signaling and kinases
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	09/2009

Abstract:

To investigate what are the DUSPs inducible by MAC/BCG to deactivate MAPK activity and suppress cytokine expression; to determine whether HIV proteins are inducers of DUSPs and suppressors of BCG/MAC-induced TNF-alpha expression; to delineate whether HIV induction of DUSPs is associated with enhanced growth of MAC/BCG.

Project Title:	Cellular response to influenza virus infection: effect of autophagy versus apoptosis on virus replication
Investigator(s):	Lau ASY, Lee DCW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	10/2009

Abstract:

To investigate whether autophagy-specific genes are activated in the avian influenza virus-infected cells, in addition to apoptosis; the global gene expression profile related to apoptosis and autophagy in avian influenza virus-infected cells and the crosstalk between apoptosis and autophagy in delzyed onset of death in avian influenza virus-infected cells by using immunomodulators or pharmacological agents.

Project Title:	Mycobacteria Evasion of Immunity: a Potential Role for IL-10 and its consequent Suppression of MHC Antigen Expression
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2009

Abstract:

1) To investigate whether IL-10 induced by BCG or MAC is capable of suppressing IFN-gamma induction of MHC class II antigen expression; 2) To define whether the effects of IL-10 or BCG/MAC on HLA-DRA act through the Jak/Stat pathways; 3) To delineate the detailed mechanisms underlying IL-10 or mycobacteria perturbation of MHC class II antigen processing and expression including the role of cathepsin S and transcription factor CIITA; 4) To utilize IL-17 to reverse the suppressive effects of IL-10 and augment IFN-gamma-induced signal transduction; 5) Significance: Investigating the mechansisms underlying mycobacteria evasion of immunity, we expect to confirm our recent findings that mycobacteria induce the expression of IL-10, which in turn inhibits IFN-gamma signal transduction resulting in the suppression of MHC class II antigen expression and consequent development of cell-mediated immunity. We expect to delineate some of the key mechanisms underlying how mycobacteria and its induced IL-10 perturb IFN-gamma signaling events such as Jak/Stat pathways and processing of MHC-II antigens. Understanding these mechanisms would provide rationales for immunotherapy. For example, we expect to confirm that the regulatory cytokine IL-17 is capable of reversing the effects of IL-10 and augment IFN-gamma induced effects. Thus, defining the mechanisms underlying these microbe-immune cell interactions would provide rationales for designing specific therapeutics to block the activity of IL-10 and to treat MTB/MAC patients with a combination of key immunoregulatory cytokines or drugs.

Project Title:	Tri-Society Annual Conference 2009 MECHANISMS UNDERLYING HIV-1 SUPPRESSION OF IFN-g SIGNALING PATHWAYS: A ROLE FOR TRANSACTIVATOR TAT IN THE INDUCTION OF SOCS-2 IN PRIMARY HUMAN BLOOD MONOCYTES
Investigator(s):	Lau ASY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2009
Completion Date:	10/2009

Abstract:

N/A

List of Research Outputs

Au K.Y., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV TAT modulation of IFN-g induced expression of autophagy-associated genes in primary human blood macrophages., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV Tat modulation of IFN- γ-induction of autophagy-associated genes in primary human blood macrophages., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. December 2-3. 2009.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV Tat modulation of IFN-γ-induced expression of autophagy-associated genes in primary human blood macrophages., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-095]. 2009.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., Travel Award, 2010 Annual General Meeting and Scientific Meeting, Hong Kong Society for Immunology, Hong Kong, April 17, 2010 . 2010.

Chan L.L.Y., Cheung B.K.W., Li C.B. and Lau A.S.Y., A role for STAT3 and cathepsin S in IL-10 down-regulation of IFN-γ-induced MHC class II molecule on primary human blood macrophages., Journal of Leukocyte Biology. 2010, 88: 1-9.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., A role for STAT3 in IL-10 downregulation of IFN-g-induced MHC class II molecule expression on primary human blood macrophages., Third Annual Scientific Meeting, The Hong Kong Society for Paediatric Immunology and Infectious Diseases Saturday, March 20, . 2010.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., A role for STAT3 in IL-10 downregulation of IFN-γ-induced MHC class II molecule expression on primary human blood macrophages., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. December 2-3. 2009.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., A role for STAT3 in IL-10 downregulation of IFN-γ-induced MHC class II molecule expression on primary human blood macrophages., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-0100]. 2009.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., Mechanisms underlying mycobacterial and HIV dysregulations of the immune system: a role for IL-10 and Stat3 dependent pathways in the suppression of interferon-g reglated cellular responses., Invited plenary session presentation for Asia Pacific Inflammation Research 2010.. 2010.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., Runner-up oral presentation Award, Third Annual Scientific Meeting, The Hong Kong Society for Paediatric Immunology and Infectious Diseases Saturday, 20th March 2010. 2010.

Chan L.L.Y., Cheung B.K.W. and Lau A.S.Y., Seymour and Vivian Milstein Travel Awards, Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009. 2009.

Cheung B.K.W., Yim H.C.H., Lee N.C.M. and Lau A.S.Y., A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1, BMC Immunology 2009 (17 Dec);10:64. 2009, 64: 1-10.

Cheung B.K.W., Yim H.C.H. and Lau A.S.Y., Positive role of mitogen-activated protein kinase phosphatase-1 in regulating the anti-mycobacterial immune response., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine-the official journal of International Cytokine Society 2009;46(1-2)PP1-071]. 2009.

Fang J.W., Yim H.C.H. and Lau A.S.Y., Interleukin-17A differentially modulates mycobacterial-induction of cytokines in human blood macrophage., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Fang J.W., Li C.B., Yim H.C.H. and Lau A.S.Y., Modulation of mycobacterium bovis (BCG)-induced cytokine response by IL-17., 9th World Congress on Inflammation 2009, Tokyo, Japan, July 8,. 2009.

Lau A.S.Y., Mechanisms underlying microbial interactions in AIDS. , RCII Seminar for Research Centre of Infection and Immunology, LKS Faculty of Medicine, HKU on 25 January 2010.. 2010.

Lau A.S.Y., Yang L.H. and Law H.Y., USA Patent Application #61/219,073: Materials and Methods for Prevention and Treatment of Viral Infections. , Type: Provisional, Priority date for IP: 12/30/2009. (Assignee/owner: HKU). 2009.

Lau A.S.Y., Yang L.H., Or C.T. and Law H.Y., USA Patent Application #61/263,517: Novel Therapeutic Methods for Treating Inflammation and Immune System Disorders., Type: Provisional, Author from HKU and Priority date for IP: 11/23/2009. (Assignee/owner: HKU). 2009.

Law H.Y., Lee D.C.W., Yuen K.Y., Peiris J.S.M. and Lau A.S.Y., Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction and implications in pathogenesis., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Lee D.C.W., Yang L.H., Chik S.C.C., Li C.B. and Lau A.S.Y., Bioactivity-guided identification and cell signaling analysis to investigate the immunomodulatory effects of ginseng on U937 cells., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP2-046]. 2009.

Lee D.C.W., Mok K.P., Law H.Y., Peiris J.S.M. and Lau A.S.Y., Differential replication of avian influenza H9N2 viruses in human alveolar epithelial A549 cells., Virol J. 2010, 7: 71.

Lee D.C.W., Lin S.S., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., Epstein-Barr virus latent membrane protein-1 induces cytokine expression through protein kinase PKR., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Lee D.C.W., Yang L.H., Chik S.C.C., Li J., Rong J., Chan G.C.F. and Lau A.S.Y., Immunomodualtory effect of Panax ginseng on human promonocytic U937 cells, Journal of Translational Medicine. 2009, 7: 34-40.

Li C.B., Cheng M., Yim H.C.H., Lee D.C.W. and Lau A.S.Y., Mechanisms underlying HIV-1 suppression of IFN-γ signaling pathways: A role for transactivator Tat in the induction of SOCS-2 in primary human blood monocytes., Tri-Society Annual Conference, Lisbon, Portugal, October 18-21. 2009.

Lin S.S., Lee D.C.W., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., A role for protein kinase PKR in the medication of Epstien-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression., Cytokine. 2010, 50(2): 210-9.

Lin S.S., Lee D.C.W., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., Best Poster Presentation Award, 2010 Annual General Meeting and Scientific Meeting, Society for Immunology, Hong Kong, April 17, 2010. 2010.

Or C.T., Yang L.H., Cheung B.K.W. and Lau A.S.Y., Mechanisms of Ligusticum chuanxiong (LCX) extracts in the suppression of proinflammatory cytokine expression in blood macrophages, 9^th World Congress on Inflammation 2009, Tokyo, Japan, 8 July. 2009.

Qi H., Wei L., Han Y., Zhang Q., Lau A.S.Y. and Rong J., Proteomic characterization of the cellular response to chemopreventive triterpenoid astragaloside IV in human hepatocellular carcinoma cell line HepG2, In: Professor DEMETRIOS A. SPANDIDOS, International Journal of Oncology. Athens, Greece, Spandidos Publications, 2010, 36: 725-735.

Qi H., Siu S.O., Chen Y., Han Y.F., Chu I.K., Tong Y., Lau A.S.Y. and Rong J., Senkyunolide isomers H and I from Rhizoma Chuanxiong attenuate hydrogen peroxide-induced oxidative stress in human liver HepG2 cells via induction of heme oxygenase-1, 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM). Nottingham, UK, 2009.

Qi H., Siu S.O., Chen Y., Han Y.F., Chu I.K., Tong Y., Lau A.S.Y. and Rong J., Senkyunolides reduce hydrogen peroxide-induced oxidative damage in human liver HepG2 cells via induction of heme oxygenase-1, Chemico-Biological Interactions. 2010, 183(3): 380-389.

Yang L.H., Wang L., Or C.T., Chik S.C.C., Li C.B. and Lau A.S.Y., Anti-inflammatory compounds from medicinal herbs capable of modulating cytokines expression in human primary blood macrophages, Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-088]. 2009.

Yang L.H., Chik S.C.C., Li C.B., Cheung B.K.W. and Lau A.S.Y., Anti-inflammatory mechanisms of black cohosh on human primary blood macrophages via its downregulation of signal transduction and transcription factor activation., 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM), Nottingham, UK, August 26-28, . 2009.

Yang L.H., Chik S.C.C., Li C.B., Cheung B.K.W. and Lau A.S.Y., Identification of the bioactive constituent and its mechanisms of action in mediating the anti-inflammatory effects of black cohosh and related Cimicifuga species on human primary blood macrophages., Journal of Medical Chemistry. 2009, 52(21): 6707-6715.

Yim H.C.H. and Lau A.S.Y., HIV-1 Tat dysregulation of lipopolysaccharide-induced cytokine responses: microbial interactions in HIV infection, AIDS. 2009, 23: 1473-84.

Yim H.C.H., Cheung B.K.W. and Lau A.S.Y., Mitogen-activated protein kinase phosphatase-1 positively regulates the anti-mycobacterial immune responses (oral presentation)., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. December 2-3,. 2009.

Researcher : Lau YL

Project Title:	A community-based educational program on thalassaemias to enhance awareness with the aim to reduce burden of thalassaemia related health problems in Hong Kong
Investigator(s):	Lau YL, Ha SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Health Promotion Projects
Start Date:	09/1997

Abstract:

To enhance the awareness of the community regarding thalassaemias; to counsel, screen and/or refer clinets who come forward to the Unit after the educational sessions; to decrease the disease burden of thalassaemias in Hong Kong as well as to serve as a possible model for southern China.

Project Title:	Comparison of process upgrade varicella vaccine (Puvv) with VARILRIX-TM
Investigator(s):	Lau YL
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Other Funding Scheme
Start Date:	07/1999

Abstract:

To evaluate and provide information on the safety, tolerability, and immunogenicity of the Process Upgrade Varicella Vaccine (PUVV) at ~16,000 or ~50,000 PFU/0.5ml compared to VARILRIX ( estimated at a release dosage of ~50,000PFU/dose) when they are concomitantly with MMRII at separate injection sites.

Project Title:	Association of cytokine and chemokine genes polymorphism with susceptibility to SARS and severity of SARS
Investigator(s):	Lau YL, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	09/2005

Abstract:

To test the association of single nucleotide polymorphisms (SNPs) and microsatellites of 6 cytokine and chemokine genes, i.e. interferon-gamma (IFN-gamma), interluekin-12 (IL-12), interleukin-10 (IL-10), tumour necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and interferon gamma-induced protein-10 (IP-10) with susceptibility to SARS; To test the association of these SNPs and microsatellites with mortality from SARS.

Project Title:	p21 gene polymorphism with systemic lupus erythematosus and rheumatoid arthritis
Investigator(s):	Lau YL, Lau WCS
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	09/2005

Abstract:

Systemic lupus erythematosus (SLE ) is a complex, multifactorial autoimmune disease that is characterized by the production of various autoantibodies. Dysregulated T cell-dependent induction of autoreactive B cells is considered to play a critical role in the development of SLE (1). The etiology and pathogenesis of SLE remain unclear, but the increased concordance rate in monozygotic twins, familial aggregation and high heritability suggested that the genetic factor is involved in the development of SLE (2-4). Cyclin-dependent kinase inhibitor 1A (also known as p21, WAF1 or CDKN1A) is a negative regulator of cyclin dependent kinases (CDKs) (5). The p21 protein encodes a 21 kDa cell cycle regulatory protein that forms quaternary complexes with the entire cyclin/CDK holoenzyme and acts as pancyclin inhibitors (6). It interacts with CDK2, CDK3, CDK4 and CDK6, thereby inhibiting the progression from the G1 to the S phase of the cell cycle (7-9). It can also bind to the replication factor proliferating cell nuclear antigen (PCNA) and inhibit DNA replication (10). The p21 gene contains the p53 binding site that is localized at 2.4 kb upstream from the translational start site and expression of p21 gene was found to be inducible by wild-type p53 gene expression (11). Moreover, several growth factors and cytokines, including interferon (IFN)-α and -γ, can modify p21 expression (12,13). As p21 is an important molecule in mediating cell cycle arrest, loss of function in p21 may favor cell proliferation. Mutations in the p21 gene have been reported to associate with development of various cancers (14-17). And cells lacking p21 gene are defective in DNA repair, which might induce impaired regulation in cell proliferation (18). Inactivating mutations of p21 lead to overexpression and hyperactivation of low-avidity, autoreactive T cells that are found in abundance in the peripheral lymphoid organs of normal individuals (19). These findings suggested that dysregulated p21 gene expression might contribute to defective cell cycle regulation and therefore lead to excessive cell proliferation and activation. The human p21 gene maps on chromosome 6p21.2 (11), which is a susceptibility region for SLE (20,21). A significant reduction in p21 gene expression is found in SLE patients as compared to controls (22). A lower expression in SLE patients is detected at various points from the G1 to G2/M phase through the S phase when compared with controls (22). Therefore, malfunction of p21 protein may contribute to the pathogenesis of systemic autoimmunity through a variety of primary or secondary mechanisms. Indeed, the p21-/- female mice with 129/Sv x C57BL/6 mixed backgrounds show development of severe lupus-like diseases followed by early mortality, high levels of anti-dsDNA antibodies and kidney immune complex deposits (23). However, the p21-/- lupus-prone BXSB mice show inhibition for the development of systemic autoimmunity (24). The p21-/- BXSB lupus-prone mice show enhancement of the Fas/FasL-mediated activation-induced T cell death and therefore promote the apoptosis of the accumulated autoreactive T and B cells, which inhibit spontaneous systemic autoimmunity (24). Although the above findings showed conflicting results for p21 deficiency, they suggested p21 gene is involved in the pathogenesis of SLE. Similar to SLE, rheumatoid arthritis (RA) is also a complex autoimmune diseases that involves genetic factors. Although disease pathogenesis remains unclear, we have previously identified the mannose binding lectin (MBL) gene as susceptibility gene in both SLE and RA (25-27) and recently, we have demonstrated that the low producing genotype of IL-10 promoter is associated with disease susceptibility and serositis in Hong Kong Chinese patients with SLE (28). The identification of susceptibility allele in SLE and RA by case-control study offers the potential for early prediction of risk of disease progression. This should also provide an approach to select the most appropriate candidate genes for intervention with new biological agents which may prevent or arrest disease progression in those at highest risk. References: Please refer to attachment [05-CRCG-SLE-References.doc]

Project Title:	Association of STAT4, ITGAM, BLK and PXK gene polymorphisms with systemic lupus erythematosus (SLE)
Investigator(s):	Lau YL, Yang W
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	09/2008

Abstract:

Systemic lupus erythematosus (SLE) is a complex, multi-factorial autoimmune disease with strong genetic involvement. Siblings of SLE patients are of 30 times higher risk of being affected than the general population [1]. Compared to Caucasians, Asians have a higher disease prevalence and more renal involvement [2, 3]. Strong population differences in genetic risk factors towards the disease have been documented by us and others [4, 5]. Recent work on genome-wide association (GWA) studies has discovered new susceptibility genes for SLE [6-9]. However, these studies were mainly conducted in populations of European origin, and it is important to examine whether those genes are also risk factors for populations of other origins. In this study, we will examine whether STAT3, ITGAM, BLK and PXK confer susceptibility risk to Chinese in Hong Kong by a case-control design of association study. We will be using the 900 plus SLE patient samples we have collected and 1,000 healthy controls obtained from Red Cross. We will choose the SNPs that were found to be associated with the disease in GWA studies but also have minor allele frequency of at least 5% in our population (based on Han Chinese in Beijing (HCB) data from HapMap) and only use the tag SNPs which don’t have good linkage disequilibrium with each other (r2<0.8). PXK is a Phox homology domain-containing serine/threonine kinase with unknown function. The gene locates in chromosome 3p14.3. SNP rs6445975 in intron 4 of PXK was found to be associated with SLE in all four sets of samples used in the study of Harley et al with P values for each set all reached below 0.05 (joint P = 7.01X10-9) [8]. The SNP has a minor allele frequency of 16.7% in HCB, so our study will have good power to detect an association if the gene also plays a role in our population. A recent study reported an association of STAT4 with disease risks of both rheumatoid arthritis and SLE. The haplotype marked by rs7574865 was found strongly associated with lupus [9]. Association of STAT4 with SLE was also confirmed in an independent study by Harley et al, both on rs7574865 and another SNP, rs7601754, which is 24 kb downstream of rs7574865 in intron 4 of the gene [8]. Both rs7574865 and rs7601754 have good MAF in Chinese population (33.3% and 14.4%, respectively), and the two SNPs has low LD with each other. So in this study we will genotype both SNPs in our samples and test whether they have independent effect on the association with the disease. BLK is a src family tyrosine kinase involved in signal transduction downstream of B cell receptor, and expression of BLK is highly restricted to B cells. The minor allele of rs13277113, a SNP located in the promoter region of BLK, was found to be associated with SLE in populations of European origin. The risk allele is also found to be related to reduced expression of BLK and increased expression of C8orf13, a gene 25 kb away from the SNP on the opposite strand [7]. Association of BLK with SLE was also confirmed by the study of Harley et al on SNP rs2248932 (OR = 1.22 P = 7X10-10) and rs10903340 (OR = 1.18, P = 1.46E-7)[8]. Rs2248932 and rs10903340 have good LD with each other and only one will be examined together with rs13277113 in our population. The product of ITGAM, integrin-M, is a molecule that combines with integrin-2 to form a leukocyte-specific integrin. The M2-integrin is important in the adherence of neutrophils and monocytes to stimulated endothelium, and in the phagocytosis of complement coated particles. The expression level of M2-integrin was found to be correlated directly with SLE disease activity [10]. In three recent studies, this gene has been found to be associated with SLE [6-8]. Harley et al showed that SNP rs9888739 located in intron 14 of ITGAM has the most significant association with SLE, but rs1143679 was not genotyped directly in this study [8]. In the study of Nath et al, both rs1143679 and rs9888739 were genotyped in the same set of samples and rs1143679 showed the most significant association in Caucasians and also in two African American populations, and was proposed to be a functional variant in the association of this gene with the disease[6]. In this study, we will genotype both rs1143679 and rs9888739 and test their association with the disease as well as any independent effect from the two variants. Reference 1. Danchenko N, et al: Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 2006, 15:308-318. 2. Chong WP, et al: Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus. Genes Immun 2004, 5:484-492. 3. Mok CC, et al: Lupus in Hong Kong Chinese. Lupus 2003, 12:717-722. 4. Willcocks LC, et al: Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake. J Exp Med 2008. 5. Clatworthy MR, et al: Systemic lupus erythematosus-associated defects in the inhibitory receptor FcgammaRIIb reduce susceptibility to malaria. Proc Natl Acad Sci U S A 2007, 104:7169-7174. 6. Nath SK, et al: A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus. Nat Genet 2008, 40:152-154. 7. Hom G, et al: Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med 2008, 358:900-909. 8. Harley JB, et al: Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 2008, 40:204-210. 9. Remmers EF, et al: STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 2007, 357:977-986. 10. Molad Y, et al: Intravascular neutrophil activation in systemic lupus erythematosus (SLE): dissociation between increased expression of CD11b/CD18 and diminished expression of L-selectin on neutrophils from patients with active SLE. Clin Immunol Immunopathol 1994, 71:281-286.

Project Title:	Immune Responses to Influenza Viruses in the Patients with X-linked Agammaglobulinemia
Investigator(s):	Lau YL, Tu W
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2008

Abstract:

(1) To determine the maturation and function of influenza virus activated dendritic cells from XLA patients in vitro We hypothesize that there are impaired maturation and function of the influenza virus activated monocyte-derived dendritic cells (MDDC) from XLA patients as defined by phenotype, cytokine production and mixed lymphocyte reaction (MLR), compared to that from normal controls; (2) To determine the influenza virus-specific CD4 and CD8 T cells responses in XLA patients in vitro We hypothesize that there are differences in influenza virus-specific CD4 and CD8 T cell responses between XLA patients and age-matched normal controls in terms of their cell number and cytokine production; (3) To determine the influenza virus-specific memory/effector CD4 and CD8 T cells in XLA patients before and after administrations of inactivated influenza vaccines. We hypothesize that XLA patients have different influenza virus-specific memory and effector CD4 and CD8 T cell responses before and after vaccination as defined by multiple phenotypic markers, cytokine secretion and tetramer staining, compared to normal controls.

Project Title:	Case-control study of Sichuan and Hong Kong children with melamine associated renal stones - renal ultasounds and urinary IL-8 and MCP-1
Investigator(s):	Lau YL, Tu W
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Studies Related to Melamine Incident
Start Date:	04/2009

Abstract:

To compare the renal ultrasound findings and the urinary IL-8 and MCP-1 in Sichuan children suffering from melaine associated renal stones with the Hong Kong chilgdren suspected to have such stones.

Project Title:	Functional characterization of two genetic variants associated with SLE identified in the Hong Kong SLE collection
Investigator(s):	Lau YL, Yang W
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	01/2010

Abstract:

Systemic Lupus Erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by autoantibody production and involvement of multiple organ systems. It shows a striking female predominance, and is more prevalent in the African and Asian populations. Genetic factors are known to play important roles to disease susceptibility [1, 2]. Work in our own group has recently documented both similarities and differences in disease susceptibility genes between our population and the Caucasians [3-5]. Our recent work, based on GWAS from Hong Kong SLE samples, identified two single nucleotide polymorphisms (SNPs), rs7859667 and rs10814451, located between the paired box 5 gene (PAX5) and maternal embryonic leucine zipper kinase (MELK) at chromosome 9, to be associated with the disease. This finding was further confirmed in four independent cohorts collected from Hong Kong, mainland China and Thailand comprising a large collection of 2953 SLE cases and 4280 controls at genome level significance (OR = 0.80, P = 1.19 x 10-9; OR = 0.76, P = 3.32 x 10-8 respectively). PAX5 and MELK demonstrated potential roles in autoimmunity developments. PAX5 encodes the transcription factor B-cell-specific activator protein (BSAP), essential to B-cell differentiation and function. The significance of PAX5 in autoimmune disease has also been suspected in a recent study of psoriasis [6, 7]. MELK is a Ser/Thr kinase that has been implicated in stem cell renewal, cell cycle progression and pre-mRNA splicing. Overexpression of wild-type MELK suppressed Bcl-GL-induced apoptosis, and thus was associated with carcinogenesis. Ineffective apoptosis can also results in accumulation of autoreactive antigens which may play a role in pathogenesis of autoimmune disease. Despite the genetic findings, the role of the two genetic variants and the potential function of the two surrounding genes in SLE pathogenesis remain unclear. In this proposal, we aim to characterize the roles of the genetic variants in the expression of PAX5 and MELK, and further, how potentially changed expression level of PAX5 and MELK may involve in SLE pathogenesis. Specifically, we will test the effect of the haplotypes formed by the two SNPs on the expression level of PAX5 and MELK in control samples and SLE patients. We will also compare the effect on healthy individuals and SLE patients and also relate any potential effect to other factors such as disease activity, and subphenotypes of the patients. Reference 1. Mok CC, et al: Lupus in Hong Kong Chinese. Lupus 2003, 12:717-722. 2. Harley I. T, et al: Genetic susceptibility to SLE: new insights from fine mapping and genome-wide association studies. Nat Rev Genet 2009, 10: 285-290. 3. W Yang, Minghui Zhao, Nattiya Hirankarn, Chak Sing Lau, Chi Chiu Mok, Tak Mao Chan, Raymond W.S. Wong, Ka Wing Lee, Mo Yin Mok, Sik Nin Wong, Yingyos Avihingsanon, Irene Oi Lin NG, Tsz Leung Lee, Marco Hok Kung Ho, Pamela Pui Wah Lee, Wilfred Hing Sang Wong, Pak Chung Sham, Yu Lung Lau, ITGAM is associated with disease susceptibility and renal nephritis of systemic lupus erythematosus in Hong Kong Chinese and Thai (Human Molecular Genetics, 18: 2063-2070, 2009) 4. Yuk Kwan Chang, W Yang, Minghui Zhao, Chi Chiu Mok, Tak Mao Chan, Raymond W.S. Wong, Ka Wing Lee, Mo Yin Mok, Sik Nin Wong, Irene Oi Lin NG, Tsz Leung Lee, Marco Hok Kung Ho, Pamela Pui Wah Lee, Wilfred Hing Sang Wong, Chak Sing Lau, 6Pak Chung Sham, Yu Lung Lau, Association of BANK1 and TNFSF4 with Systemic Lupus Erythematosus in Hong Kong Chinese (Genes and Immunity, 2009, in press) 5. W. Yang , Ping Ng , MingHui Zhao , Nattiya Hirankarn , Chak Sing Lau , Chi Chiu Mok , Tak-Mo Chan , Raymond Wong , Ka Wing Lee , Mo Yin Mok , Sik Nin Wong , Yingyos Avihingsanon , Tsz Leung Lee , Marco Ho , Pamela Lee , Hing-Sang Wong, Yulung Lau, Population differences in SLE susceptibility genes--STAT4 and BLK, but not PXK, are associated with Systemic Lupus Erythematosus in Hong Kong Chinese (Genes & Immunity, 10: 219-226, 2009) 6. Smith, R. L, et al: Polymorphisms in the PTPN22 region are associated with psoriasis of early onset. Br J Dermatol 2008, 5: 962-968. 7. Kingo, K, et al: Association analysis of IL20RA and IL20RB genes in psoriasis. Genes Immun 2008, 5: 445-451.

List of Research Outputs

Chiu S.S.S., Chan K.H., Tu W., Lau Y.L. and Peiris J.S.M., Immunogenicity and safety of intradermal versus intramuscular route of influenza immunization in infants less than 6 months of age: a randomized controlled trial, Vaccine. 2009, 27(35): 4834-9.

Chiu S.S.S., Chan K.H., Chen H., Young B.W., Lim W., Wong W.H.S., Lau Y.L. and Peiris J.S.M., Virologically confirmed population-based burden of hospitalization caused by influenza A and B among children in Hong Kong, Clinical Infectious Diseases. 2009, 49: 1016-1021.

Chong W.P., Zhou J., Law H.K.W., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells., European Journal of Immunology.. 2010, 40: 1718-1727.

Chong W.P., Zhou J., Law H.K., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells, Eur J Immunol. 2010, 40(6): 1718-27.

Chong W.P., Zhou J., Law H.K.W., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells, European Journal of Immunology. 2010, 40: 1-10.

Ho M.H.K., Lee S.B.H., Wong W.H.S. and Lau Y.L., Peanut oil and peanut allergy, foes or folks?, Archives of Disease in Childhood [Epub in print]. 2010, 1-2.

Lau S.K.P., Yip C.Y., Lin A.W., Lee R.A., So L.Y., Lau Y.L., Chan K.H., Woo P.C.Y. and Yuen K.Y., Clinical and molecular epidemiology of human rhinovirus C in children and adults in Hong Kong reveals a possible distinct human rhinovirus C subgroup, Journal of Infectious Diseases. 2009, 200(7): 1096-1103.

Lau Y.L., A New Era of Paediatric Service, Hospital Authority Convention 2010.

Lau Y.L., Genetic diagnosis for primary immunodeficiencies in China, 4th Annual Scientific Meeting, Macau Pediatric Society. 2009.

Lau Y.L., Promoting PID care in Asia through e-consultation and free genetic diagnosis, 2nd Asia Pacific Symposium on Primary Immunodeficiency Disease. 2010.

Lee P.P.W., Chen T.X., Jiang L.P., Chan K.W., Yang W., Lee B.W., Chiang W.C., Chen X.Y., Fok S.F.S., Lee T.L., Ho M.H.K., Yang X.Q. and Lau Y.L., Clinical Characteristics and Genotype-phenotype Correlation in 62 patients with X-linked Agammaglobulinemia, Journal of Clinical Immunology. 2010, 30: 121-131.

Lee P.P.W., Lee T.L., Ho M.H.K., Zeng H.S., Chen X.Y., Chan K.W., Tu W. and Lau Y.L., Invasive Penicillium marneffel Infection in Children without Acquired Immunodeficiency Syndrome (AIDS) - An Indicator Disease for Primary Immunodeficiency?, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W., Chan K.W., Chen T.X., Jiang L.P., Wang X.C., Zeng H.S., Chen X.Y., Lee B.W., Shek L., Liew W.K., Lee C.W., Yu H.H., Latiff Z.A., Ho M.H.K., Lee T.L. and Lau Y.L., Molecular diagnosis of severe combined immunodeficiency - Identification of IL2RG, JAK3, IL7R, DCLRE1C and RAG2 mutations in a cohort of Chinese and Southeast Asian children, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W., Lau Y.L., Ho M.H.K., Lee T.L. and Chan K.W., Primary Immunodeficiency Referral Network in Asia: Database Review 2001 – 2009, Young Investigator Award, 6th Congress of Asian Society for Pediatric Research . 2010.

Lee P.P.W., Chan K.W., Wong W.H.S., Ho M.H.K., Lee T.L. and Lau Y.L., Primary Immunodeficiency Referral Network in Asia: Database Review 2001-2009, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W. and Lau Y.L., Primary immunodeficiencies: "new" disease in an old country, Cellular & Molecular Immunology. 2009, 6: 397-406.

Lee P.P.W., Chung B.H.Y., Chan S.Y. and Lau Y.L., Teaching and Learning Medical Genetics - An Interactive Genetics Workshop for Paediatric Clerkship Students, First Runner-up,, Best Poster Presentation: 7^th Asia Pacific Medical Education Conference (APMEC): Excellence in Medical Education - Quality in Healthcare (Trends, Issues, Priorities, Strategies), Medical Education Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 4-8 Februray 2010.

Lee P.P.W., Chung B.H.Y., Chan S.Y. and Lau Y.L., Teaching and Learning Medical Genetics - An Interactive Workshop for Undergraduate Medical Students, 7th Asia Pacific Medical Education Conference, Runner up Poster presenter. 2010.

Li W.S., Hung I.F.N., To K.K.W., Chan K.H., Wong S.S.Y., Chan J.F.W., Cheng V.C.C., Tsang O.T., Lai S.T., Lau Y.L. and Yuen K.Y., The natural viral load profile of patients with pandemic swine-origin influenza A H1N1 2009 (pH1N1) and the effect of oseltamivir treatment., Chest. 2010, 137: 759-768.

Liu Y., Zheng J., Lau Y.L. and Tu W., Intrinsic IFN-gamma-T-bet pathway mediates the Generation of Th1-like regulatory T cells induced by CD40-activated B cells, FOCIS meeting. 2010.

Lum L.C.S., Borja-Tabora C.F., Breiman R.F., Vesikari T., Sablan B.P., Chay O.M., Tantracheewathorn T., Schmitt H.J., Lau Y.L., Bowonkiratikachorn P., Tam J.S., Lee B.W., Tan K.K., Pejcz J., Cha S., Gutierrez-Brito M., Kaltenis P., Vertruyen A., Czajka H., Bojarskas J., Brooks W.A., Cheng S.M., Rappaport R., Baker S., Gruber W.C. and Forrest B.D., Influenza vaccine concurrently administered with a combination measles, mumps, and rubella vaccine to young children, Vaccine. 2009, 28: 1566-1574.

Mao H., Tu W., Qin G., Law H.K., Sia S.F., Chan P.L., Liu Y., Lam K.T., Zheng J., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, J Virol. 2009, 83(18): 9215-22.

Mao H., Tu W., Qin G., Lau H.K.W., Chan P.L., Liu Y., Lam K.T., Zhang Y., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, Journal of Virology. 2009, 83: 9215-9222.

Mao H., Tu W., Liu Y., Qin G., Zheng J., Chan P.L., Lam K.T., Peiris J.S.M. and Lau Y.L., Inhibition of human natural killer cell activity by influenza virions and hemagglutinin, J Virol. 2010, 84(9): 4148-57.

Phua K.B., Lim F.S., Lau Y.L., Nelson E.A.S., Huang L.M., Quak S.H., Lee B.W., Teoh Y.L., Tang H., Boudville I., Oostvogels L.C., Suryakiran P.V., Smolenov I.V., Han H.H. and Bock H.L., Safety and efficacy of human rotavirus vaccine during the first 2 years of life in Asian infants: randomised, double-blind, controlled study, Vaccine. 2009, 27: 5936-5941.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded Human Gammadelta T Cells Display Potent Cytotoxicities Towards Human and Avian Influenza Virus-infected Monocyte-derived Macrophages, clinical immunology. 2009, 131: s91-s92.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded gammadelta T cells display potent cytotoxicity against human and avian influenza virus-infected monocyte-derived macrophages, Journal of Infectious Diseases. 2009, 200: 858-865.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Lam K.T., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses, J Infect Dis. 2009, 200(6): 858-65.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 Influenza A virus, Journal of Medical Virology. 2010, 82: 1-7.

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Hung I.F.N., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 influenza A virus, J Med Virol. 2010, 82: 1-7.

Tso H.W., Law H.K.W., Tu W., Chan G.C.F. and Lau Y.L., Phagocytosis of apoptotic cells modulates mesenchymal stem cells osteogenic differentiation to enhance IL-17 and RANKL expression on CD4+ T cells, Stem Cells. 2010, 28: 939-954.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Tu W., Qin G., Liu Y. and Lau Y.L., Non-cytolytic antiviral activity of phosphoanntigen-Expanded Human Gammadelta T cells Against influenza virus, FOCIS meeting. 2010.

Tu W., Qin G. and Lau Y.L., Non-cytolytic antiviral activity of phosphoanntigen-expanded human Gammadelta T cells against influenza virus, FOCIS meeting. 2010.

Tu W., Zheng J., Liu Y. and Lau Y.L., Stimulatory or tolerohenic role of CD40-activated B cells depends on the strength of the activation to T cells, blood. U.S.A., 2009, 114: 747-748.

Willcocks L.C., Carr E.J., Niederer H.A., Rayner T.F., Williams T.N., Yang W., Scott J.A., Urban B.C., Peshu N., Vyse T.J., Lau Y.L., Lyons P.A. and Smith K.G., A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus. , Proceedings of the National Academy of Sciences of the United States of America . 2010, 107: 7881-7885.

Willcocks L.C., Carr E.J., Niederer H.A., Rayner T.F., Williams T.N., Yang W., Scott J.A.G., Urban B.C., Peshu N., Vyse T.J., Lau Y.L., Lyons P.A. and Smith K.G.C., A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus, Proceedings of the National Academy of Sciences. 2010, 107(17): 7881-7885.

Yang W., Shen N., Ye D.Q., Liu Q., Qian X.X., Hirankarn N., Pan H.F., Mok C.C., Chan D.T.M., Wong R.W.S., Lee K.W., Wong S.N., Leung A.M.H., Li X.P., Avihingsanon Y., Wong C.M., Lee T.L., Ho M.H.K., Lee P.P.W., Chang Y.K., Li P.H., Li R., Zhang L., Wong W.H.S., Ng I.O.L., Lau W.C.S., Sham P.C., Lau Y.L. and Asian Lupus Genetics Consortium A.L.G.C., Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. , PLoS Genetics. 2010, 6: e1000841.

Zheng J., Liu Y., Lau Y.L. and Tu W., CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4(+) regulatory T cells, Cell Mol Immunol. 2010, 7(1): 44-50.

Zheng J., Liu Y., Lau Y.L. and Tu W., CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4+ regulatory T cells, Cellular & Molecular Immunology. 2010, 7: 44-50.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., lewis D.B., Lau Y.L. and Tu W., Efficient Induction and Expansion of Human Alloantigen-Specific CD8 Regulatory T Cells from Naive Precursors by CD40-Activated B Cells. , Journal of Immunology. U.S.A., 2009, 2009 Aug 14.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., Lewis D.B., Lau Y.L. and Tu W., Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells, J Immunol. 2009, 183(6): 3742-50.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H.W., Lewis D.B., Lau Y.L. and Tu W., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, Clinical Immunology. 2009, 131: S163-S163.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lewis D.B. and Lau Y.L., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, clinical immunology. 2009.

Researcher : Law HKW

List of Research Outputs

Chong W.P., Zhou J., Law H.K.W., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells., European Journal of Immunology.. 2010, 40: 1718-1727.

Chong W.P., Zhou J., Law H.K.W., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells, European Journal of Immunology. 2010, 40: 1-10.

Tso H.W., Law H.K.W., Tu W., Chan G.C.F. and Lau Y.L., Phagocytosis of apoptotic cells modulates mesenchymal stem cells osteogenic differentiation to enhance IL-17 and RANKL expression on CD4+ T cells, Stem Cells. 2010, 28: 939-954.

Researcher : Law HY

List of Research Outputs

Lau A.S.Y., Yang L.H. and Law H.Y., USA Patent Application #61/219,073: Materials and Methods for Prevention and Treatment of Viral Infections. , Type: Provisional, Priority date for IP: 12/30/2009. (Assignee/owner: HKU). 2009.

Lau A.S.Y., Yang L.H., Or C.T. and Law H.Y., USA Patent Application #61/263,517: Novel Therapeutic Methods for Treating Inflammation and Immune System Disorders., Type: Provisional, Author from HKU and Priority date for IP: 11/23/2009. (Assignee/owner: HKU). 2009.

Law H.Y., Lee D.C.W., Yuen K.Y., Peiris J.S.M. and Lau A.S.Y., Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction and implications in pathogenesis., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Lee D.C.W., Mok K.P., Law H.Y., Peiris J.S.M. and Lau A.S.Y., Differential replication of avian influenza H9N2 viruses in human alveolar epithelial A549 cells., Virol J. 2010, 7: 71.

Lee D.C.W., Lin S.S., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., Epstein-Barr virus latent membrane protein-1 induces cytokine expression through protein kinase PKR., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Lin S.S., Lee D.C.W., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., A role for protein kinase PKR in the medication of Epstien-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression., Cytokine. 2010, 50(2): 210-9.

Lin S.S., Lee D.C.W., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., Best Poster Presentation Award, 2010 Annual General Meeting and Scientific Meeting, Society for Immunology, Hong Kong, April 17, 2010. 2010.

Researcher : Lee CW

List of Research Outputs

Lee P.P.W., Chan K.W., Chen T.X., Jiang L.P., Wang X.C., Zeng H.S., Chen X.Y., Lee B.W., Shek L., Liew W.K., Lee C.W., Yu H.H., Latiff Z.A., Ho M.H.K., Lee T.L. and Lau Y.L., Molecular diagnosis of severe combined immunodeficiency - Identification of IL2RG, JAK3, IL7R, DCLRE1C and RAG2 mutations in a cohort of Chinese and Southeast Asian children, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Researcher : Lee CY

List of Research Outputs

Huen K.F., Low L.C.K., Cheung P.T., Wong G.W.K., But B.W.M., Kwan E.Y.W., Lam Y.Y., Lee C.Y., Wong L.M., Ng K.L., Cheng A.W.F., Tong C.T. and Wong W.H.S., An Update on the Epidemiology of Childhood Diabetes in Hong Kong , Hong Kong Journal of Paediatrics . 2009, 14: 252-259.

Researcher : Lee DCW

List of Research Outputs

Law H.Y., Lee D.C.W., Yuen K.Y., Peiris J.S.M. and Lau A.S.Y., Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction and implications in pathogenesis., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Lee D.C.W., Yang L.H., Chik S.C.C., Li C.B. and Lau A.S.Y., Bioactivity-guided identification and cell signaling analysis to investigate the immunomodulatory effects of ginseng on U937 cells., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP2-046]. 2009.

Lee D.C.W., Mok K.P., Law H.Y., Peiris J.S.M. and Lau A.S.Y., Differential replication of avian influenza H9N2 viruses in human alveolar epithelial A549 cells., Virol J. 2010, 7: 71.

Lee D.C.W., Lin S.S., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., Epstein-Barr virus latent membrane protein-1 induces cytokine expression through protein kinase PKR., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Lee D.C.W., Yang L.H., Chik S.C.C., Li J., Rong J., Chan G.C.F. and Lau A.S.Y., Immunomodualtory effect of Panax ginseng on human promonocytic U937 cells, Journal of Translational Medicine. 2009, 7: 34-40.

Li C.B., Cheng M., Yim H.C.H., Lee D.C.W. and Lau A.S.Y., Mechanisms underlying HIV-1 suppression of IFN-γ signaling pathways: A role for transactivator Tat in the induction of SOCS-2 in primary human blood monocytes., Tri-Society Annual Conference, Lisbon, Portugal, October 18-21. 2009.

Lin S.S., Lee D.C.W., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., A role for protein kinase PKR in the medication of Epstien-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression., Cytokine. 2010, 50(2): 210-9.

Lin S.S., Lee D.C.W., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., Best Poster Presentation Award, 2010 Annual General Meeting and Scientific Meeting, Society for Immunology, Hong Kong, April 17, 2010. 2010.

Researcher : Lee PPW

List of Research Outputs

Chen J.Y. and Lee P.P.W., Continuous assessment, In: LK Chan and NG Patil, Assessment in Medical and Health Sciences Education. Hong Kong, IMHSE, 2009, 31-45.

Koh C., Lee P.P.W., Yung T.C., Lun K.S. and Cheung Y.F., Left ventricular noncompaction in children, Cogenital Heart Disease. 2009, 4: 288-294.

Lam C.L.K., Chan G.C.F., Lam T.H., Lee P.P.W., Leung A.Y.M., Leung G.K.K. and Tsao G.S.W., 育醫造才: 探索醫學世界, 2010.

Lee P.P.W., Chen T.X., Jiang L.P., Chan K.W., Yang W., Lee B.W., Chiang W.C., Chen X.Y., Fok S.F.S., Lee T.L., Ho M.H.K., Yang X.Q. and Lau Y.L., Clinical Characteristics and Genotype-phenotype Correlation in 62 patients with X-linked Agammaglobulinemia, Journal of Clinical Immunology. 2010, 30: 121-131.

Lee P.P.W., Lee T.L., Ho M.H.K., Zeng H.S., Chen X.Y., Chan K.W., Tu W. and Lau Y.L., Invasive Penicillium marneffel Infection in Children without Acquired Immunodeficiency Syndrome (AIDS) - An Indicator Disease for Primary Immunodeficiency?, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W., Chan K.W., Chen T.X., Jiang L.P., Wang X.C., Zeng H.S., Chen X.Y., Lee B.W., Shek L., Liew W.K., Lee C.W., Yu H.H., Latiff Z.A., Ho M.H.K., Lee T.L. and Lau Y.L., Molecular diagnosis of severe combined immunodeficiency - Identification of IL2RG, JAK3, IL7R, DCLRE1C and RAG2 mutations in a cohort of Chinese and Southeast Asian children, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W., Lau Y.L., Ho M.H.K., Lee T.L. and Chan K.W., Primary Immunodeficiency Referral Network in Asia: Database Review 2001 – 2009, Young Investigator Award, 6th Congress of Asian Society for Pediatric Research . 2010.

Lee P.P.W., Chan K.W., Wong W.H.S., Ho M.H.K., Lee T.L. and Lau Y.L., Primary Immunodeficiency Referral Network in Asia: Database Review 2001-2009, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W. and Lau Y.L., Primary immunodeficiencies: "new" disease in an old country, Cellular & Molecular Immunology. 2009, 6: 397-406.

Lee P.P.W., Chung B.H.Y., Chan S.Y. and Lau Y.L., Teaching and Learning Medical Genetics - An Interactive Genetics Workshop for Paediatric Clerkship Students, First Runner-up,, Best Poster Presentation: 7^th Asia Pacific Medical Education Conference (APMEC): Excellence in Medical Education - Quality in Healthcare (Trends, Issues, Priorities, Strategies), Medical Education Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 4-8 Februray 2010.

Lee P.P.W., Chung B.H.Y., Chan S.Y. and Lau Y.L., Teaching and Learning Medical Genetics - An Interactive Workshop for Undergraduate Medical Students, 7th Asia Pacific Medical Education Conference, Runner up Poster presenter. 2010.

Yang W., Shen N., Ye D.Q., Liu Q., Qian X.X., Hirankarn N., Pan H.F., Mok C.C., Chan D.T.M., Wong R.W.S., Lee K.W., Wong S.N., Leung A.M.H., Li X.P., Avihingsanon Y., Wong C.M., Lee T.L., Ho M.H.K., Lee P.P.W., Chang Y.K., Li P.H., Li R., Zhang L., Wong W.H.S., Ng I.O.L., Lau W.C.S., Sham P.C., Lau Y.L. and Asian Lupus Genetics Consortium A.L.G.C., Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. , PLoS Genetics. 2010, 6: e1000841.

Researcher : Lee SBH

List of Research Outputs

Ho M.H.K., Lee S.B.H., Wong W.H.S. and Lau Y.L., Peanut oil and peanut allergy, foes or folks?, Archives of Disease in Childhood [Epub in print]. 2010, 1-2.

Researcher : Lee SL

List of Research Outputs

Chan S.H.S., Fung C.W., Yung A.W.Y., Lee S.L., Wong V.C.N., Dale R.C. and Vincent A.C., Anti-NMDA-R encephalitis - an encephalitis lerthargica-like illness, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Chan S.H.S., Wong V.C.N., Fung C.W., Dale R.C., Vincent A., Yung A.W.Y. and Lee S.L., Anti-NMDAR encephalitis - An encephalitis lethargica like illness, 11^th International Child Neurology Congress, Cairo, Egypt, 2-7 May 2010. The International Journal of Child Neuropsychiatry (poster presentaion). 2010, 184.

Researcher : Lee TL

List of Research Outputs

Lee P.P.W., Chen T.X., Jiang L.P., Chan K.W., Yang W., Lee B.W., Chiang W.C., Chen X.Y., Fok S.F.S., Lee T.L., Ho M.H.K., Yang X.Q. and Lau Y.L., Clinical Characteristics and Genotype-phenotype Correlation in 62 patients with X-linked Agammaglobulinemia, Journal of Clinical Immunology. 2010, 30: 121-131.

Lee P.P.W., Lee T.L., Ho M.H.K., Zeng H.S., Chen X.Y., Chan K.W., Tu W. and Lau Y.L., Invasive Penicillium marneffel Infection in Children without Acquired Immunodeficiency Syndrome (AIDS) - An Indicator Disease for Primary Immunodeficiency?, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W., Chan K.W., Chen T.X., Jiang L.P., Wang X.C., Zeng H.S., Chen X.Y., Lee B.W., Shek L., Liew W.K., Lee C.W., Yu H.H., Latiff Z.A., Ho M.H.K., Lee T.L. and Lau Y.L., Molecular diagnosis of severe combined immunodeficiency - Identification of IL2RG, JAK3, IL7R, DCLRE1C and RAG2 mutations in a cohort of Chinese and Southeast Asian children, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Lee P.P.W., Lau Y.L., Ho M.H.K., Lee T.L. and Chan K.W., Primary Immunodeficiency Referral Network in Asia: Database Review 2001 – 2009, Young Investigator Award, 6th Congress of Asian Society for Pediatric Research . 2010.

Lee P.P.W., Chan K.W., Wong W.H.S., Ho M.H.K., Lee T.L. and Lau Y.L., Primary Immunodeficiency Referral Network in Asia: Database Review 2001-2009, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Wong S.N., Chan W.K.Y., Hui J., Chim S., Lee T.L., Lee K.P., Leung L.C.K., Tse N.K.C. and So Y.F., Membranous lupus nephritis in Chinese children - a case series and review of the literature, Pediatric Nephrology. 2009, 24: 1989-1996.

Yang W., Shen N., Ye D.Q., Liu Q., Qian X.X., Hirankarn N., Pan H.F., Mok C.C., Chan D.T.M., Wong R.W.S., Lee K.W., Wong S.N., Leung A.M.H., Li X.P., Avihingsanon Y., Wong C.M., Lee T.L., Ho M.H.K., Lee P.P.W., Chang Y.K., Li P.H., Li R., Zhang L., Wong W.H.S., Ng I.O.L., Lau W.C.S., Sham P.C., Lau Y.L. and Asian Lupus Genetics Consortium A.L.G.C., Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. , PLoS Genetics. 2010, 6: e1000841.

Researcher : Leung CW

List of Research Outputs

To K.K.W., Chan K.H., Li W.S., Tsang T.Y., Tse H., Chan J.F.W., Lai S.T., Leung C.W., Kwan Y.W., Lau Y.L., Ng T.K., Cheng V.C.C., Peiris J.S.M. and Yuen K.Y., Viral load in patients infected with pandemic H1N1 2009 Influenza A virus, Journal of Medical Virology. 2010, 82: 1-7.

Researcher : Li CB

Project Title:	Enhancement of innate immunity to the pathogen infection: anti-mycobacterial effect of IL-17
Investigator(s):	Li CB, Lau ASY
Department:	Medical Faculty
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	12/2009

Abstract:

(1) To further examine the mechanisms underlying how IL-17 contributes to the anti-mycobacterial activities of macrophages including production of nitric oxide and cytokines, induction of signaling kinases and bactericidal actions against MTB and Mycobacteria avium complex (MAC); (2) to study the effects of IL-17 in optimizing anti-mycobacterial effects such as nitric oxide production and induction of cytokines; (3) to test whether exogenous IL-17 can be used to enhance the innate immune system in a mouse model and further considered for use as an adjunctive therapy for MTB or MAC

List of Research Outputs

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV Tat modulation of IFN- γ-induction of autophagy-associated genes in primary human blood macrophages., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. December 2-3. 2009.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV Tat modulation of IFN-γ-induced expression of autophagy-associated genes in primary human blood macrophages., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-095]. 2009.

Fang J.W., Li C.B., Yim H.C.H. and Lau A.S.Y., Modulation of mycobacterium bovis (BCG)-induced cytokine response by IL-17., 9th World Congress on Inflammation 2009, Tokyo, Japan, July 8,. 2009.

Lee D.C.W., Yang L.H., Chik S.C.C., Li C.B. and Lau A.S.Y., Bioactivity-guided identification and cell signaling analysis to investigate the immunomodulatory effects of ginseng on U937 cells., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP2-046]. 2009.

Li C.B., Cheng M., Yim H.C.H., Lee D.C.W. and Lau A.S.Y., Mechanisms underlying HIV-1 suppression of IFN-γ signaling pathways: A role for transactivator Tat in the induction of SOCS-2 in primary human blood monocytes., Tri-Society Annual Conference, Lisbon, Portugal, October 18-21. 2009.

Yang L.H., Wang L., Or C.T., Chik S.C.C., Li C.B. and Lau A.S.Y., Anti-inflammatory compounds from medicinal herbs capable of modulating cytokines expression in human primary blood macrophages, Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-088]. 2009.

Yang L.H., Chik S.C.C., Li C.B., Cheung B.K.W. and Lau A.S.Y., Anti-inflammatory mechanisms of black cohosh on human primary blood macrophages via its downregulation of signal transduction and transcription factor activation., 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM), Nottingham, UK, August 26-28, . 2009.

Yang L.H., Chik S.C.C., Li C.B., Cheung B.K.W. and Lau A.S.Y., Identification of the bioactive constituent and its mechanisms of action in mediating the anti-inflammatory effects of black cohosh and related Cimicifuga species on human primary blood macrophages., Journal of Medical Chemistry. 2009, 52(21): 6707-6715.

Researcher : Li J

List of Research Outputs

Lee D.C.W., Yang L.H., Chik S.C.C., Li J., Rong J., Chan G.C.F. and Lau A.S.Y., Immunomodualtory effect of Panax ginseng on human promonocytic U937 cells, Journal of Translational Medicine. 2009, 7: 34-40.

Researcher : Li R

List of Research Outputs

Yang W., Shen N., Ye D.Q., Liu Q., Qian X.X., Hirankarn N., Pan H.F., Mok C.C., Chan D.T.M., Wong R.W.S., Lee K.W., Wong S.N., Leung A.M.H., Li X.P., Avihingsanon Y., Wong C.M., Lee T.L., Ho M.H.K., Lee P.P.W., Chang Y.K., Li P.H., Li R., Zhang L., Wong W.H.S., Ng I.O.L., Lau W.C.S., Sham P.C., Lau Y.L. and Asian Lupus Genetics Consortium A.L.G.C., Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. , PLoS Genetics. 2010, 6: e1000841.

Researcher : Liang X

List of Research Outputs

Cheung E.W.Y., Liang X., Lam W.W.M. and Cheung Y.F., Impact of right ventricular dilation on left ventricular myocardial deformation in patients after surgical repair of Tetralogy of Fallot, American Journal of Cardiology. 2009, 104: 1264-1270.

Cheung Y.F., Liang X., Chan G.C.F., Wong S.J. and Ha S.Y., Myocardial deformation in patients with beta-thalassemia major: a speckle tracking echocardiographic study , Echocardiography. 2010, 27: 253-259.

Liang X., Lam W.W.M., Cheung E.W.Y., Wu A.K.P., Wong S.J. and Cheung Y.F., Restrictive Right Ventricular Physiology and Right Ventricular Fibrosis as Assessed by Cardiac Magnetic Resonance and Exercise Capacity After Biventricular Repair of Pulmonary Atresia and Intact Ventricular Septum , Clinical Cardiology . 2010, 33: 104-110.

Researcher : Lin SS

List of Research Outputs

Lee D.C.W., Lin S.S., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., Epstein-Barr virus latent membrane protein-1 induces cytokine expression through protein kinase PKR., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Lin S.S., Lee D.C.W., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., A role for protein kinase PKR in the medication of Epstien-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression., Cytokine. 2010, 50(2): 210-9.

Lin S.S., Lee D.C.W., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., Best Poster Presentation Award, 2010 Annual General Meeting and Scientific Meeting, Society for Immunology, Hong Kong, April 17, 2010. 2010.

Researcher : Liu Y

List of Research Outputs

Liu Y., Zheng J., Lau Y.L. and Tu W., Intrinsic IFN-gamma-T-bet pathway mediates the Generation of Th1-like regulatory T cells induced by CD40-activated B cells, FOCIS meeting. 2010.

Mao H., Tu W., Qin G., Law H.K., Sia S.F., Chan P.L., Liu Y., Lam K.T., Zheng J., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, J Virol. 2009, 83(18): 9215-22.

Mao H., Tu W., Qin G., Lau H.K.W., Chan P.L., Liu Y., Lam K.T., Zhang Y., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, Journal of Virology. 2009, 83: 9215-9222.

Mao H., Tu W., Liu Y., Qin G., Zheng J., Chan P.L., Lam K.T., Peiris J.S.M. and Lau Y.L., Inhibition of human natural killer cell activity by influenza virions and hemagglutinin, J Virol. 2010, 84(9): 4148-57.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded Human Gammadelta T Cells Display Potent Cytotoxicities Towards Human and Avian Influenza Virus-infected Monocyte-derived Macrophages, clinical immunology. 2009, 131: s91-s92.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded gammadelta T cells display potent cytotoxicity against human and avian influenza virus-infected monocyte-derived macrophages, Journal of Infectious Diseases. 2009, 200: 858-865.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Lam K.T., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses, J Infect Dis. 2009, 200(6): 858-65.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Tu W., Qin G., Liu Y. and Lau Y.L., Non-cytolytic antiviral activity of phosphoanntigen-Expanded Human Gammadelta T cells Against influenza virus, FOCIS meeting. 2010.

Tu W., Zheng J., Liu Y. and Lau Y.L., Stimulatory or tolerohenic role of CD40-activated B cells depends on the strength of the activation to T cells, blood. U.S.A., 2009, 114: 747-748.

Zheng J., Liu Y., Lau Y.L. and Tu W., CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4(+) regulatory T cells, Cell Mol Immunol. 2010, 7(1): 44-50.

Zheng J., Liu Y., Lau Y.L. and Tu W., CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4+ regulatory T cells, Cellular & Molecular Immunology. 2010, 7: 44-50.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., lewis D.B., Lau Y.L. and Tu W., Efficient Induction and Expansion of Human Alloantigen-Specific CD8 Regulatory T Cells from Naive Precursors by CD40-Activated B Cells. , Journal of Immunology. U.S.A., 2009, 2009 Aug 14.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., Lewis D.B., Lau Y.L. and Tu W., Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells, J Immunol. 2009, 183(6): 3742-50.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H.W., Lewis D.B., Lau Y.L. and Tu W., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, Clinical Immunology. 2009, 131: S163-S163.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lewis D.B. and Lau Y.L., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, clinical immunology. 2009.

Researcher : Low LCK

Project Title:	12th Asia Pacific Congress of Paediatrics and 2nd Asia Pacific Congress of Paediatric Nursing The Role of Nutritional Intake and Total Energy Expenditure on Early Growth of Babies Born with Intrauterine Growth Retardation
Investigator(s):	Low LCK
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	09/2006

Abstract:

N/A

List of Research Outputs

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Siu S., Mak C.M., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitter assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD)(Diamond Prize). 2010.

Fung C.W., Siu S., Blau N., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November, 2009.. 2009.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Blau N., Siu S., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S., Siu S. and Wong V.C.N., Spectrum of mitochondrial diseases in a tertiary referral centre in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Huen K.F., Low L.C.K., Cheung P.T., Wong G.W.K., But B.W.M., Kwan E.Y.W., Lam Y.Y., Lee C.Y., Wong L.M., Ng K.L., Cheng A.W.F., Tong C.T. and Wong W.H.S., An Update on the Epidemiology of Childhood Diabetes in Hong Kong , Hong Kong Journal of Paediatrics . 2009, 14: 252-259.

Low L.C.K., Associate Editor (Endocrinology) , Pediatric Research 2010 . 2010.

Low L.C.K., Chairperson, Diabetic session of 13th Asian Pacific Congress of Paediatrics and 3rd Asian Pacific Congress of Pediatric Nursing, Shanghai, PR China, 14-18 October , 2009.

Low L.C.K., Chairperson, Clinical conundrums, 11th Asian Pacific Paaediatric Endocrine Faculty meeting, Ayutthaya, Thailand. 9 - 11 October 2009. 2009.

Low L.C.K., Childhood Rickets (兒童佝僂病的診斷與治療進展). 2010年國家繼續教育基地項目，小兒內分泌遺傳代謝病學習班. Chongqing, China 11-13 June 2010. , 2010.

Low L.C.K., Chinese Endocrinology Society Symposium (生長發育相關基礎與臨床研究研討會), Changsha, PR China, 15 – 17 January. , 2010.

Low L.C.K., Chinese Society of Pediatric Endocrinology and Metabolism (中國兒童及青少年糖尿病胰島素治療指南)專家審稿會, Kunming, PR China, 26 – 28 March 2010. , 2010.

Low L.C.K., Diabetes and Obesity , 11th Asia Pacific Paediatric Endocrine Society Fellows Meeting, Ayutthaya, Thailand. 9 - 11 October, 2009.

Low L.C.K., Disorders of sexual differentiation, Guangzhou Women and Children's Medical Center, Education Program of IEM and Pediatric Endocrinology, 17 - 20 September 2009. 2009.

Low L.C.K., Disorders of the thyroid gland. 2010復旦大學附屬兒科醫院內分泌遺傳代謝學術論壇. Shanghai, China 27 – 30 May 2010. , 2010.

Low L.C.K., Disorders of the thyroid gland, Medical Continued Educational Course and Pediatric Endocrinology Forum. Capital Medical University, Beijing Children's Hospital. Beijing, PR China, 7 - 10 May 2010. 2010.

Low L.C.K., Editorial Board Member, Chinese Journal of Evidence-Based Pediatrics, 2010.

Low L.C.K., Growth hormone treatment in idiopathic short stature, Macau Pediatric Seminar 2009, Macau, 11 July 2009.

Low L.C.K., International Editorial Board Member, World Journal of Pediatrics, 2010.

Low L.C.K., Metabolic Bone Disorders, Advances in the Diagnosis and Management of Pediatric Genetic Metabolic and Endocrine Disorders National CME Course, Tongji Hospital, Wuhan, PR China. 14 - 18 December. 2009.

Low L.C.K., Molecular defects in Human Growth, 2010復旦大學附屬兒科醫院內分泌遺傳代謝學術論壇. Shanghai, China, 27 – 30 May 2010., 2010.

Low L.C.K., Precocious Puberty , Advances in the Diagnosis and Management of Pediatric Genetic Metabolic and Endocrine Disorders National CME Course, Tongji Hospital, Wuhan, PR China. 14 - 18 December . 2009.

Low L.C.K., Precocious puberty , Joint ESPE and Chinese Society of Pediatric Endocrinology and Metabolic Disease Senior Fellows Training Course. Yangzhou, PR Chinia. 3 - 4 November . 2009.

Low L.C.K., Safety Issues of Growth Hormone Treatment. Chinese Society of Pediatric Endocrinology and Metabolism (ISS 專題研討會), Hangzhou, PR China, 17 – 19 April 2010, 2010.

Low L.C.K., The Epidemic of Type 2 Diabetes Mellitus, (Editorial), Hong Kong Journal of Paediatrics. Medcom, 2009, 14: 231-235.

Low L.C.K., The emerging epidemic of type 2 diabetes in children. 13th Asia Pacific Congress of Paediatrics and 3rd Asian Pacific Congress of Pediatric Nursing. Shanghai, 14 - 18 October 2009, 2009.

Low L.C.K., The epidemic of type 2 diabetes mellitus in the Asia-Pacific region. Pediatric Diabetes (Editorial), 2010, 11: 212-215.

Low L.C.K., The management of idiopathic short stature, 13th Asian Pacific Congress of Pediatrics and 3rd Asian Pacific Congress of Pediatric Nursing, Shanghai, PR China, 14 - 18 October 2009 . 2009.

Low L.C.K., Thyroid Disorder. 11th Asia Pacific Paediatric Endocrine Society Fellow Meeting. Ayutthaya, Thailand. 9 - 11 October 2009, 2009.

Low L.C.K., Type 2 diabetes in the Youth. ABC Series of Symposia on Diabetes:Y, Hong Kong Society of Endocrinology Metabolism and Reproduction Diabetes Division. 29 April 2010. 2010.

Low L.C.K., Type 2 diabetes mellitus in childhood and adolescence. , Joint ESPE and Chinese Society of Pediatric Endocrinology and Metabolic Disease Senior Fellows Training Course. Yangzhou, PR China. 3 - 4 November. 2009.

Low L.C.K., 兒童中肥胖與糖尿病一型及二型之關係, 澳門中華醫學會, 2010年1月10日, 2010.

Mak C.M., Lam C.W., Siu T.S., Chan K.Y., Siu C.W.K., Yeung W.L., Hui J., Wong V.C.N., Low L.C.K., Ko C.H., Tam S. and Chan Y.W., Biochemical and molecular characterization of tyrosine hydroxylase deficiency in Hong Kong Chinese, Molecular Genetics and Metabolism. 2010, 99(4): 431-433.

Poon G.W.K., Kwok A.M.K., Cheung P.T., Yung T.C., Ng Y.K., Tsoi N.S., Wong K.Y. and Low L.C.K., Variable Response to Enzyme Replacement Therapy in Two Chinese Children with Infantile-onset Pompe Disease in Hong Kong , Hong Kong Journal of Paediatrics. 2009, 14: 243-251.

Researcher : Lun KS

List of Research Outputs

Hong W., Yung T.C., Lun K.S., Wong S.J. and Cheung Y.F., Impact of right ventricular pacing on three-dimensional global left ventricular dyssynchrony in children and young adults with congenital and acquired heart block associated with congenital heart disease , The American Journal of Cardiology. 2009, 104: 700-706.

Hong W., Yung T.C., Lun K.S., Wong S.J. and Cheung Y.F., Impact of temporary interruption of right ventricular pacing for heart block on left ventricular function and dyssynchrony. , Pacing and Clinical Electrophysiology. 2010, 33: 41-48.

Ko L.Y., Chau A.K.T., Yung T.C., Cheung Y.F. and Lun K.S., Retrospective Review on Anomalous Left Coronary Artery from Pulmonary Artery , Hong Kong Journal of Paediatrics . 2010, 15: 12-18.

Koh C., Lee P.P.W., Yung T.C., Lun K.S. and Cheung Y.F., Left ventricular noncompaction in children, Cogenital Heart Disease. 2009, 4: 288-294.

Li X., Cheng L.C., Cheung Y.F., Lun K.S., Chau A.K.T. and Chiu S.W., Management of symptomatic congenital tracheal stenosis in neonates and infants by slide tracheoplasty: a 7-year single institution experience, European Journal of Cardio-thoracic Surgery. 2010, 38: 609-614.

Lun K.S., Fan K., Yung T.C., Wong K.T., Cheung Y.F., Chau A.K.T. and Cheng L.C., Experience of pediatric heart transplantation in Hong Kong, International Congress of Cardiology, Hong Kong, 26-28 February 2010.

Lun K.S., Fan K., Wong C.F., Yung T.C., Chow P.C., Wong K.T., Cheung Y.F., Chow W.H., Chau A.K.T., Chiu S.W. and Cheng L.C., Outcome of thoracic organ transplantation for adults with congenital heart disease, 18^th Annual Scientific Congress, Hong Kong College of Cardiology, Hong Kong, 14-16 May 2010.

Tso W.W.Y., Yung A.W.Y., Lun K.S., Yung T.C., Fan K. and Wong V.C.N., Posterior Reversible Encephalopathy Syndrome (PRES): Paediatric heart transplant with cyclosporine neurotoxicity, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Researcher : Ma M

List of Research Outputs

Ma M. and Chan G.C.F., Human mesenchymal stromal cells derived chemokines with potential involvement in neuroblastoma metastasis., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Researcher : Mao H

List of Research Outputs

Mao H., Tu W., Qin G., Law H.K., Sia S.F., Chan P.L., Liu Y., Lam K.T., Zheng J., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, J Virol. 2009, 83(18): 9215-22.

Mao H., Tu W., Qin G., Lau H.K.W., Chan P.L., Liu Y., Lam K.T., Zhang Y., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, Journal of Virology. 2009, 83: 9215-9222.

Mao H., Tu W., Liu Y., Qin G., Zheng J., Chan P.L., Lam K.T., Peiris J.S.M. and Lau Y.L., Inhibition of human natural killer cell activity by influenza virions and hemagglutinin, J Virol. 2010, 84(9): 4148-57.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded Human Gammadelta T Cells Display Potent Cytotoxicities Towards Human and Avian Influenza Virus-infected Monocyte-derived Macrophages, clinical immunology. 2009, 131: s91-s92.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded gammadelta T cells display potent cytotoxicity against human and avian influenza virus-infected monocyte-derived macrophages, Journal of Infectious Diseases. 2009, 200: 858-865.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Lam K.T., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses, J Infect Dis. 2009, 200(6): 858-65.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., lewis D.B., Lau Y.L. and Tu W., Efficient Induction and Expansion of Human Alloantigen-Specific CD8 Regulatory T Cells from Naive Precursors by CD40-Activated B Cells. , Journal of Immunology. U.S.A., 2009, 2009 Aug 14.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., Lewis D.B., Lau Y.L. and Tu W., Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells, J Immunol. 2009, 183(6): 3742-50.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lewis D.B. and Lau Y.L., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, clinical immunology. 2009.

Researcher : Mao H

List of Research Outputs

Researcher : Mok SP

List of Research Outputs

Ha S.Y., Mok S.P., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*. , Hemoglobin. 2009, 33(5): 323-331.

Ha S.Y., Mok S.P., Chu W.C.W., Rasalkar D.D., Cheuk D.K.L., Chiang A.K.S., Ho M.H.K. and Chan G.C.F., A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and MRI cardiac T2*., Hemoglobin (Proceedings of the 17th International Conference on Chelation (ICOC), Shenzhen, PR China 23-27 November 2007).. 2009, 33(5): 323-331.

Researcher : Ng KL

List of Research Outputs

Huen K.F., Low L.C.K., Cheung P.T., Wong G.W.K., But B.W.M., Kwan E.Y.W., Lam Y.Y., Lee C.Y., Wong L.M., Ng K.L., Cheng A.W.F., Tong C.T. and Wong W.H.S., An Update on the Epidemiology of Childhood Diabetes in Hong Kong , Hong Kong Journal of Paediatrics . 2009, 14: 252-259.

Researcher : Ng P

List of Research Outputs

Fung C.W., Chung B.H.Y., Ng P., Zhao M., Yang W. and Wong V.C.N., Infantile Convulsion Choreoathetosis Syndrome in a Hong Kong Chinese Family, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Researcher : Ng YK

List of Research Outputs

Poon G.W.K., Kwok A.M.K., Cheung P.T., Yung T.C., Ng Y.K., Tsoi N.S., Wong K.Y. and Low L.C.K., Variable Response to Enzyme Replacement Therapy in Two Chinese Children with Infantile-onset Pompe Disease in Hong Kong , Hong Kong Journal of Paediatrics. 2009, 14: 243-251.

Researcher : Or CT

List of Research Outputs

Lau A.S.Y., Yang L.H., Or C.T. and Law H.Y., USA Patent Application #61/263,517: Novel Therapeutic Methods for Treating Inflammation and Immune System Disorders., Type: Provisional, Author from HKU and Priority date for IP: 11/23/2009. (Assignee/owner: HKU). 2009.

Or C.T., Yang L.H., Cheung B.K.W. and Lau A.S.Y., Mechanisms of Ligusticum chuanxiong (LCX) extracts in the suppression of proinflammatory cytokine expression in blood macrophages, 9^th World Congress on Inflammation 2009, Tokyo, Japan, 8 July. 2009.

Yang L.H., Wang L., Or C.T., Chik S.C.C., Li C.B. and Lau A.S.Y., Anti-inflammatory compounds from medicinal herbs capable of modulating cytokines expression in human primary blood macrophages, Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-088]. 2009.

Researcher : Poon GWK

List of Research Outputs

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Siu S., Mak C.M., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitter assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD)(Diamond Prize). 2010.

Fung C.W., Siu S., Blau N., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November, 2009.. 2009.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Blau N., Siu S., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S., Siu S. and Wong V.C.N., Spectrum of mitochondrial diseases in a tertiary referral centre in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Poon G.W.K., Kwok A.M.K., Cheung P.T., Yung T.C., Ng Y.K., Tsoi N.S., Wong K.Y. and Low L.C.K., Variable Response to Enzyme Replacement Therapy in Two Chinese Children with Infantile-onset Pompe Disease in Hong Kong , Hong Kong Journal of Paediatrics. 2009, 14: 243-251.

Researcher : Qin G

List of Research Outputs

Mao H., Tu W., Qin G., Law H.K., Sia S.F., Chan P.L., Liu Y., Lam K.T., Zheng J., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, J Virol. 2009, 83(18): 9215-22.

Mao H., Tu W., Qin G., Lau H.K.W., Chan P.L., Liu Y., Lam K.T., Zhang Y., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, Journal of Virology. 2009, 83: 9215-9222.

Mao H., Tu W., Liu Y., Qin G., Zheng J., Chan P.L., Lam K.T., Peiris J.S.M. and Lau Y.L., Inhibition of human natural killer cell activity by influenza virions and hemagglutinin, J Virol. 2010, 84(9): 4148-57.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded Human Gammadelta T Cells Display Potent Cytotoxicities Towards Human and Avian Influenza Virus-infected Monocyte-derived Macrophages, clinical immunology. 2009, 131: s91-s92.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded gammadelta T cells display potent cytotoxicity against human and avian influenza virus-infected monocyte-derived macrophages, Journal of Infectious Diseases. 2009, 200: 858-865.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Lam K.T., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses, J Infect Dis. 2009, 200(6): 858-65.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Tu W., Qin G., Liu Y. and Lau Y.L., Non-cytolytic antiviral activity of phosphoanntigen-Expanded Human Gammadelta T cells Against influenza virus, FOCIS meeting. 2010.

Tu W., Qin G. and Lau Y.L., Non-cytolytic antiviral activity of phosphoanntigen-expanded human Gammadelta T cells against influenza virus, FOCIS meeting. 2010.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., lewis D.B., Lau Y.L. and Tu W., Efficient Induction and Expansion of Human Alloantigen-Specific CD8 Regulatory T Cells from Naive Precursors by CD40-Activated B Cells. , Journal of Immunology. U.S.A., 2009, 2009 Aug 14.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., Lewis D.B., Lau Y.L. and Tu W., Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells, J Immunol. 2009, 183(6): 3742-50.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H.W., Lewis D.B., Lau Y.L. and Tu W., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, Clinical Immunology. 2009, 131: S163-S163.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lewis D.B. and Lau Y.L., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, clinical immunology. 2009.

Researcher : Qin G

List of Research Outputs

Tu W., Qin G., Liu Y. and Lau Y.L., Non-cytolytic antiviral activity of phosphoanntigen-Expanded Human Gammadelta T cells Against influenza virus, FOCIS meeting. 2010.

Tu W., Qin G. and Lau Y.L., Non-cytolytic antiviral activity of phosphoanntigen-expanded human Gammadelta T cells against influenza virus, FOCIS meeting. 2010.

Researcher : So LY

List of Research Outputs

Lau S.K.P., Yip C.Y., Lin A.W., Lee R.A., So L.Y., Lau Y.L., Chan K.H., Woo P.C.Y. and Yuen K.Y., Clinical and molecular epidemiology of human rhinovirus C in children and adults in Hong Kong reveals a possible distinct human rhinovirus C subgroup, Journal of Infectious Diseases. 2009, 200(7): 1096-1103.

Researcher : Tao KP

List of Research Outputs

Tao K.P. and Chan S.Y., Functional analysis of Tspyl2 in cell proliferation, The British Association for Cancer Research/The European Association for Cancer Research, Chromatin and Cancer Symposium, Cambrigde, UK, 6-8 Julyy 2009.

Tao K.P., Lai S.K., Chan Y.S., Sham M.H. and Chan S.Y., Tspyl2 is involved in Cellular Stress Response and Brain Function, 14^th Research Postgraduate Symposium, HKU, 2-3 December 2009.

Tsang K.H., Tao K.P., Lai S.K., Chan Y.S. and Chan S.Y., Tspy 12 regulates hippocampal long-term potentiation via NMDA receptor subunits Nr2a and Nr2b expression, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010. 2010.

Tsang K.H., Tao K.P., Lai S.K., Chan Y.S. and Chan S.Y., Tspy12 regulates hippocampal long-term potentiation via NMDA receptor subunits Nr2a and Nr2b expression, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010.

Researcher : Tao KP

List of Research Outputs

Tao K.P., Lai S.K., Chan Y.S., Sham M.H. and Chan S.Y., Tspyl2 is involved in Cellular Stress Response and Brain Function, 14^th Research Postgraduate Symposium, HKU, 2-3 December 2009.

Tsang K.H., Tao K.P., Lai S.K., Chan Y.S. and Chan S.Y., Tspy12 regulates hippocampal long-term potentiation via NMDA receptor subunits Nr2a and Nr2b expression, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010.

Researcher : Ting JY

List of Research Outputs

Ting J.Y., Wong M.S.C., Wong R.M.S. and Wong K.Y., Changes in Epidemioloyg of Extremely Low Birth Weight Infants (ELBW): Implications for Resource Use, 13^th Asian Pacific Congress of Pediatrics, Shanghai, PR China, 14 October 2009.

Ting J.Y. and Cheung P.Y., [Letters to the Editor] Cerebral blood flow velocities in extremely low birth weight infants, The Journal of Pediatrics. 2009, 155(6): 944.

Researcher : Tong CT

List of Research Outputs

Huen K.F., Low L.C.K., Cheung P.T., Wong G.W.K., But B.W.M., Kwan E.Y.W., Lam Y.Y., Lee C.Y., Wong L.M., Ng K.L., Cheng A.W.F., Tong C.T. and Wong W.H.S., An Update on the Epidemiology of Childhood Diabetes in Hong Kong , Hong Kong Journal of Paediatrics . 2009, 14: 252-259.

Researcher : Tsang KH

List of Research Outputs

Chan S.Y., Wong H.T. and Tsang K.H., The nucleosome assembly protein TSPYL2 represses transcription, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010.

Tsang K.H., Best presentation award for an excellent presentation, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010. 2010.

Tsang K.H., Lai S.K., Chan Y.S. and Chan S.Y., Testis-specific Protein Y-linked-Like 2 (Tspyl2) Regulates Hippocampal Long-term Potentiation via NMDA Receptors Expression and p38MAPK Activity, 14^th Research Postgraduate Symposium, HKU, 2-3 December 2009.

Tsang K.H., Tao K.P., Lai S.K., Chan Y.S. and Chan S.Y., Tspy 12 regulates hippocampal long-term potentiation via NMDA receptor subunits Nr2a and Nr2b expression, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010. 2010.

Tsang K.H., Tao K.P., Lai S.K., Chan Y.S. and Chan S.Y., Tspy12 regulates hippocampal long-term potentiation via NMDA receptor subunits Nr2a and Nr2b expression, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010.

Researcher : Tsang KH

List of Research Outputs

Tsang K.H., Tao K.P., Lai S.K., Chan Y.S. and Chan S.Y., Tspy12 regulates hippocampal long-term potentiation via NMDA receptor subunits Nr2a and Nr2b expression, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010.

Researcher : Tso HW

List of Research Outputs

Tso H.W., Law H.K.W., Tu W., Chan G.C.F. and Lau Y.L., Phagocytosis of apoptotic cells modulates mesenchymal stem cells osteogenic differentiation to enhance IL-17 and RANKL expression on CD4+ T cells, Stem Cells. 2010, 28: 939-954.

Researcher : Tso WWY

List of Research Outputs

Tso W.W.Y., Yung A.W.Y., Lun K.S., Yung T.C., Fan K. and Wong V.C.N., Posterior Reversible Encephalopathy Syndrome (PRES): Paediatric heart transplant with cyclosporine neurotoxicity, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Researcher : Tsoi NS

List of Research Outputs

Chan K.L., Fan S.T., Lo C.M., Wei W.I., Ng W.M., Chung H.Y., Ng K.K.C., Chan S.C., Chan K.W., Tso W.K., Tsoi N.S. and Tam P.K.H., Pediatric liver transplantation in Hong Kong - a domain with scarce deceased donors, Journal of Pediatric Surgery. 2009, 44(12): 2316-2321.

Chung P.H.Y., Wong K.K.Y., Wong R.M.S., Tsoi N.S., Chan K.L. and Tam P.K.H., Clinical experience in managing pediatric patients with ultra-short bowel syndrome using Omega-3 fatty acid, European Journal of Pediatric Surgery. 2010, 20(2): 139-142.

Poon G.W.K., Kwok A.M.K., Cheung P.T., Yung T.C., Ng Y.K., Tsoi N.S., Wong K.Y. and Low L.C.K., Variable Response to Enzyme Replacement Therapy in Two Chinese Children with Infantile-onset Pompe Disease in Hong Kong , Hong Kong Journal of Paediatrics. 2009, 14: 243-251.

Researcher : Tu W

Project Title:	Humanized mouse as a model to study the antiviral activity of human gammadelta-T cells against human and avian influenza A viruses in vivo
Investigator(s):	Tu W, Lau YL, Peiris JSM, Law HKW
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Research Fund for the Control of Infectious Diseases - Full Grants
Start Date:	08/2007

Abstract:

Humanized mouse carrying human immune system with or without gammadelta-T cells will be generated study: (1) whether human gammadelta-T cells have antiviral activities against human and avian flu viruses in vivo? (2) whether PA can be used for treatment of human and avian fluA virus infections in vivo?

Project Title:	Immune defense of human gammadelta-T cells against Influenza a viruses
Investigator(s):	Tu W, Lau YL, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2008
Completion Date:	12/2009

Abstract:

To determine the antiviral cytokine responses of gammadelta-T cells in response to human and avian fluA viruses as compared to NK cells and monocytes; to determine how gammadelta-T cells help NK cells and modulate monocyte-derived macrophages (MDM) during human and avian fluA virus infections; to determine the chemokine expressions and chemotactic receptor phenotype of effector (IFN-gamma-positive) gammadelta-T cells in response to human and avian fluA viruses; to determine the antiviral potential of PA-activated gammadelta-T cells against human and avian fluA viruses.

Project Title:	The Role of Natural Killer Cells in the Pathogenesis of Avian Influenza Virus Infection
Investigator(s):	Tu W, Cheung CY, Lau YL
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2009

Abstract:

(1) To determine the mechanisms underlying the decreased cytotoxicities of human NK cells during avian fluA infections. We hypothesize that these decreased cytotoxicities are mediated through the hyper-induction of proinflammatory cytokines/chemokines and/or interference of the balance of NK cell activating and inhibitory receptors. We further hypothesize that the decreased cytotoxicity of NK cells may account for the hyperinflammatory cytokine secretions and uncontrolled viral replication in macrophages; (2) To determine whether there is a decreased cytotoxicity of NK cells during avian fluA H5N1 infection in vivo using a murine model. We hypothesize that there is a reduced cytotoxicity of NK cells during the H5N1 infection in vivo as compared to H1N1 infection, and this decreased cytotoxicity may account for high viral load and hyperinflammtory cytokines in the lung; (3) To determine whether there is an increased apoptosis of NK cells during avian fluA H5N1 infection in vivo using a murine model. We hypothesize that there is no increased apoptosis of murine NK cells during H5N1 infection in vivo as we found that in human in vitro preliminary study, compared to H1N1 infection; (4) To determine whether the approaches to enhance the NK cell cytotoxicity may provide protection against lethal H5N1 virus challenge using a murine model. We hypothesize that the adoptive transfer of activated-NK cells may provide protection against lethal H5N1 virus challenge in mice. (5) To determine the differential chemotactic receptor profile of the lung-associated NK cells in mice upon avian fluA virus infections. We hypothesize that murine lung-associated NK cells display a different and distinct chemotactic receptor profile as compared to NK cell populations in circulation and spleen during human and avian fluA infections. We also hypothesize that there are different chemotactic receptor profiles between NK cells infected with the different strains of human and avian fluA viruses.

List of Research Outputs

Chiu S.S.S., Chan K.H., Tu W., Lau Y.L. and Peiris J.S.M., Immunogenicity and safety of intradermal versus intramuscular route of influenza immunization in infants less than 6 months of age: a randomized controlled trial, Vaccine. 2009, 27(35): 4834-9.

Chong W.P., Zhou J., Law H.K.W., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells., European Journal of Immunology.. 2010, 40: 1718-1727.

Chong W.P., Zhou J., Law H.K., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells, Eur J Immunol. 2010, 40(6): 1718-27.

Chong W.P., Zhou J., Law H.K.W., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells, European Journal of Immunology. 2010, 40: 1-10.

Lee P.P.W., Lee T.L., Ho M.H.K., Zeng H.S., Chen X.Y., Chan K.W., Tu W. and Lau Y.L., Invasive Penicillium marneffel Infection in Children without Acquired Immunodeficiency Syndrome (AIDS) - An Indicator Disease for Primary Immunodeficiency?, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Liu Y., Zheng J., Lau Y.L. and Tu W., Intrinsic IFN-gamma-T-bet pathway mediates the Generation of Th1-like regulatory T cells induced by CD40-activated B cells, FOCIS meeting. 2010.

Mao H., Tu W., Qin G., Law H.K., Sia S.F., Chan P.L., Liu Y., Lam K.T., Zheng J., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, J Virol. 2009, 83(18): 9215-22.

Mao H., Tu W., Qin G., Lau H.K.W., Chan P.L., Liu Y., Lam K.T., Zhang Y., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, Journal of Virology. 2009, 83: 9215-9222.

Mao H., Tu W., Liu Y., Qin G., Zheng J., Chan P.L., Lam K.T., Peiris J.S.M. and Lau Y.L., Inhibition of human natural killer cell activity by influenza virions and hemagglutinin, J Virol. 2010, 84(9): 4148-57.

Peiris J.S.M., Tu W., Yen H., Peiris J.S.M. and Yen H., A novel H1N1 virus causes the first pandemic of the 21st century, Eur J Immunol. 2009, 39(11): 2946-54.

Peiris J.S.M., Tu W. and Yen H., A novel H1N1 virus causes the first pandemic of the 21^st century, European Journal of Immunology. 2009, 39: 2946-2954.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded Human Gammadelta T Cells Display Potent Cytotoxicities Towards Human and Avian Influenza Virus-infected Monocyte-derived Macrophages, clinical immunology. 2009, 131: s91-s92.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded gammadelta T cells display potent cytotoxicity against human and avian influenza virus-infected monocyte-derived macrophages, Journal of Infectious Diseases. 2009, 200: 858-865.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Lam K.T., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses, J Infect Dis. 2009, 200(6): 858-65.

Tso H.W., Law H.K.W., Tu W., Chan G.C.F. and Lau Y.L., Phagocytosis of apoptotic cells modulates mesenchymal stem cells osteogenic differentiation to enhance IL-17 and RANKL expression on CD4+ T cells, Stem Cells. 2010, 28: 939-954.

Tu W., Antiviral immunity in infants and children, 13th Asian Pacific Congress of Pediatrics and 3rd Asian Pacific Congress of Pediatric Nursing. . Shanghai, China, 2009.

Tu W., Antiviral immunity in infants and children, Viral Infection Symposijm at 13^th Asian Pacific Congress of Pediatric and 3^rd Asian Pacific Congress of Pediatric Nursing, Shanghai, PR China, 14-18 October 2009.

Tu W., CD40-activated B cells: stimulatory or tolerogenic APC, In: Chinese Association of Immunology, Immunology Forum for Great China Areas, Guangzhou. 2009.

Tu W., CD40-activated B cells: stimulatory or tolerogenic APC, Immunology summit conference (China, Hong Kong & Taiwan). Guangzhou, 2009.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Tu W., Editor, Cellular & Molecular Immunology. 2010.

Tu W., From bench to bedside: Understanding and Manipulation of the Lymphocyte Responses to Viral- and Allo-antigens, In: Chongqing Medical University, Pediatric Medical Forum 2010. Chongqing, China, 2010.

Tu W., From bench to bedside: Understanding and Maniputation of the Lymphocyte Responses to Viral-and Allo-antigens, Zhujiang Forum: Transplantation Immunology, Guangzhou, PR China, 7 January 2010.

Tu W., From bench to bedside: the application of human regulatory T cells, In: Southern Medical University, Zhujiang Forum: Transplantation Immunology. Guangzhou, 2010.

Tu W., Qin G., Liu Y. and Lau Y.L., Non-cytolytic antiviral activity of phosphoanntigen-Expanded Human Gammadelta T cells Against influenza virus, FOCIS meeting. 2010.

Tu W., Qin G. and Lau Y.L., Non-cytolytic antiviral activity of phosphoanntigen-expanded human Gammadelta T cells against influenza virus, FOCIS meeting. 2010.

Tu W., Zheng J., Liu Y. and Lau Y.L., Stimulatory or tolerohenic role of CD40-activated B cells depends on the strength of the activation to T cells, blood. U.S.A., 2009, 114: 747-748.

Tu W., Understanding and Manipulation of the Lymphocyte Responses to Viral- and Allo-antigens, The Third Military Medical University. Chongqing, China, 2009.

Tu W., Understanding and Manipulation of the Lymphocyte Responses to Viral- and Allo-antigens, The Third Military Medical University, Chongqing, PR China, 25 December 2009.

Zheng J., Liu Y., Lau Y.L. and Tu W., CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4(+) regulatory T cells, Cell Mol Immunol. 2010, 7(1): 44-50.

Zheng J., Liu Y., Lau Y.L. and Tu W., CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4+ regulatory T cells, Cellular & Molecular Immunology. 2010, 7: 44-50.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., lewis D.B., Lau Y.L. and Tu W., Efficient Induction and Expansion of Human Alloantigen-Specific CD8 Regulatory T Cells from Naive Precursors by CD40-Activated B Cells. , Journal of Immunology. U.S.A., 2009, 2009 Aug 14.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., Lewis D.B., Lau Y.L. and Tu W., Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells, J Immunol. 2009, 183(6): 3742-50.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H.W., Lewis D.B., Lau Y.L. and Tu W., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, Clinical Immunology. 2009, 131: S163-S163.

Researcher : Wang L

List of Research Outputs

Yang L.H., Wang L., Or C.T., Chik S.C.C., Li C.B. and Lau A.S.Y., Anti-inflammatory compounds from medicinal herbs capable of modulating cytokines expression in human primary blood macrophages, Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-088]. 2009.

Researcher : Wong CL

List of Research Outputs

Wong V.C.N., Li L., Lam S.S., Wong C.L. and Chu V.L.Y., Pilot project of integration of Chinese medicine (acupuncture) and western medicine for neurohabilitation of children with acquired brain injury - a study of 2 cases, 19th World Congress of Neurology, Bangkok, Thailand, 24-30 October 2009.

Researcher : Wong HT

List of Research Outputs

Chan S.Y., Wong H.T. and Tsang K.H., The nucleosome assembly protein TSPYL2 represses transcription, 43^rd Annual Meeting for the Japanese Society of Developmental Biologists (Jointly sponsored by the Asia-Pacific Developmental Biology Network), Japan, 20-23 June 2010.

Wong H.T., Chiu R.P.H. and Chan S.Y., A role of TSPYL2, a novel nucleosome assembly protein, in transcriptional regulation, The British Association for Cancer Research/The European Association for Cancer Research, Chromatin and Cancer Symposium, Cambrigde, UK, 6-8 Julyy 2009.

Researcher : Wong KT

List of Research Outputs

Lun K.S., Fan K., Yung T.C., Wong K.T., Cheung Y.F., Chau A.K.T. and Cheng L.C., Experience of pediatric heart transplantation in Hong Kong, International Congress of Cardiology, Hong Kong, 26-28 February 2010.

Lun K.S., Fan K., Wong C.F., Yung T.C., Chow P.C., Wong K.T., Cheung Y.F., Chow W.H., Chau A.K.T., Chiu S.W. and Cheng L.C., Outcome of thoracic organ transplantation for adults with congenital heart disease, 18^th Annual Scientific Congress, Hong Kong College of Cardiology, Hong Kong, 14-16 May 2010.

Researcher : Wong KY

List of Research Outputs

Poon G.W.K., Kwok A.M.K., Cheung P.T., Yung T.C., Ng Y.K., Tsoi N.S., Wong K.Y. and Low L.C.K., Variable Response to Enzyme Replacement Therapy in Two Chinese Children with Infantile-onset Pompe Disease in Hong Kong , Hong Kong Journal of Paediatrics. 2009, 14: 243-251.

Ting J.Y., Wong M.S.C., Wong R.M.S. and Wong K.Y., Changes in Epidemioloyg of Extremely Low Birth Weight Infants (ELBW): Implications for Resource Use, 13^th Asian Pacific Congress of Pediatrics, Shanghai, PR China, 14 October 2009.

Researcher : Wong LM

List of Research Outputs

Huen K.F., Low L.C.K., Cheung P.T., Wong G.W.K., But B.W.M., Kwan E.Y.W., Lam Y.Y., Lee C.Y., Wong L.M., Ng K.L., Cheng A.W.F., Tong C.T. and Wong W.H.S., An Update on the Epidemiology of Childhood Diabetes in Hong Kong , Hong Kong Journal of Paediatrics . 2009, 14: 252-259.

Researcher : Wong MSC

List of Research Outputs

Ting J.Y., Wong M.S.C., Wong R.M.S. and Wong K.Y., Changes in Epidemioloyg of Extremely Low Birth Weight Infants (ELBW): Implications for Resource Use, 13^th Asian Pacific Congress of Pediatrics, Shanghai, PR China, 14 October 2009.

Researcher : Wong RMS

List of Research Outputs

Chung P.H.Y., Wong K.K.Y., Wong R.M.S., Tsoi N.S., Chan K.L. and Tam P.K.H., Clinical experience in managing pediatric patients with ultra-short bowel syndrome using Omega-3 fatty acid, European Journal of Pediatric Surgery. 2010, 20(2): 139-142.

Ting J.Y., Wong M.S.C., Wong R.M.S. and Wong K.Y., Changes in Epidemioloyg of Extremely Low Birth Weight Infants (ELBW): Implications for Resource Use, 13^th Asian Pacific Congress of Pediatrics, Shanghai, PR China, 14 October 2009.

Researcher : Wong SJ

List of Research Outputs

Cheung Y.F., Hong W., Chan G.C.F., Wong S.J. and Ha S.Y., Left ventricular myocardial deformation and mechanical dyssychrony in chidlren with normal ventricular shortening fraction after anthracyline therapy , The 6th Korea-Japan-China Pediatric Heart Forum, March 26-27, Seoul, Korea. 2010.

Cheung Y.F., Liang X., Chan G.C.F., Wong S.J. and Ha S.Y., Myocardial deformation in patients with beta-thalassemia major: a speckle tracking echocardiographic study , Echocardiography. 2010, 27: 253-259.

Hong W., Yung T.C., Lun K.S., Wong S.J. and Cheung Y.F., Impact of right ventricular pacing on three-dimensional global left ventricular dyssynchrony in children and young adults with congenital and acquired heart block associated with congenital heart disease , The American Journal of Cardiology. 2009, 104: 700-706.

Hong W., Yung T.C., Lun K.S., Wong S.J. and Cheung Y.F., Impact of temporary interruption of right ventricular pacing for heart block on left ventricular function and dyssynchrony. , Pacing and Clinical Electrophysiology. 2010, 33: 41-48.

Liang X., Lam W.W.M., Cheung E.W.Y., Wu A.K.P., Wong S.J. and Cheung Y.F., Restrictive Right Ventricular Physiology and Right Ventricular Fibrosis as Assessed by Cardiac Magnetic Resonance and Exercise Capacity After Biventricular Repair of Pulmonary Atresia and Intact Ventricular Septum , Clinical Cardiology . 2010, 33: 104-110.

Researcher : Wong SN

List of Research Outputs

Wong S.N., Chan W.K.Y., Hui J., Chim S., Lee T.L., Lee K.P., Leung L.C.K., Tse N.K.C. and So Y.F., Membranous lupus nephritis in Chinese children - a case series and review of the literature, Pediatric Nephrology. 2009, 24: 1989-1996.

Yang W., Shen N., Ye D.Q., Liu Q., Qian X.X., Hirankarn N., Pan H.F., Mok C.C., Chan D.T.M., Wong R.W.S., Lee K.W., Wong S.N., Leung A.M.H., Li X.P., Avihingsanon Y., Wong C.M., Lee T.L., Ho M.H.K., Lee P.P.W., Chang Y.K., Li P.H., Li R., Zhang L., Wong W.H.S., Ng I.O.L., Lau W.C.S., Sham P.C., Lau Y.L. and Asian Lupus Genetics Consortium A.L.G.C., Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. , PLoS Genetics. 2010, 6: e1000841.

Researcher : Wong VCN

Project Title:	Rett Syndrome :Systematic screening of MECP2 in children with autistic traits and or unexplained mental retardation/ encephalopathy to define the spectrum of Rett Syndrome phenotypes resulting from mutations in MECP2
Investigator(s):	Wong VCN
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	01/2006

Abstract:

Rett syndrome (RTT) is an X-linked dominant neurodegenerative disorder characterized by a period of early normal growth and development followed by regression with loss of speech, acquired motor skills, stereotypic hand movement, and seizures. RTT affects 1 in 15,000 females and is the second leading cause of profound mental retardation in females. RTT is a clinical syndrome without any diagnostic biologic markers and the pathophysiologic changes has not been identified. The diagnosis of RTT is still reliant on clinical criteria. Early diagnosis of RS in the normal developmental period is still impossible. The disease is caused by mutations in the methyl-CpG-binding protein 2 gene (MECP2), and various mutations have been reported. The phenotypic spectrum in both female and male patients is diverse, ranging from very mild to congenital encephalopathy and prenatal lethality. Methyl-CpG binding protein 2 (MECP2) The responible gene, encoding Methyl-CpG binding protein 2 (MECP2) is discovered (1999 Sept 30). (1,2) MECP2 mutations is detected in < 50% of girls with RS by PCR amplification of the coding region. The RTT phenotype of MECP2 mutation is broad with lethality and normality in the two extremes. Findings have suggested that X-Chromosome Inactivation (XCI) pattern is the major determinant of the phenotype in females. MECP2 is an abundant chromosome-binding protein that selectively binds 5-methyl cytosine residues in CpG dinucleotides of mammalian genome. MECP2 has a role as a global transcriptional repressor in vertebrate genome. However, how MECP2 mutation cause RTT is still unclear as only 50% of RS girls has the mutation. MECP2 mutations has been detected by PCR amplification of the coding region. As MECP2 mutations could also involve the highly conserved regions within the 8.5-kb 3’UTR, mutational analysis should expand to include this region as well. Until now, MECP2 mutations has been detected by PCR amplification of the coding region in 60% of girls with RS. Possibly MECP2 mutations in the highly conserved regions within the 8.5-kb 3’UTR are currently underway. Both nonsense and missense mutations have been found. Different single-nucleotide deletion or insertion was found in patients with RS. Others are the nucleotide substitutions, which involve C-T transitions at CpG hotspots except one variant (G-A). Clinical Spectrum of Rett syndrome: The spectrum of phenotypes of MECP2 mutations seems to be much broader. R168X mutation was found in 2 affected sisters and their normal mother. In one family, an 806 del G deletion causing a V288X stop in the transcription-repression domain was identified in a woman with mild neuropyschological problems and skewed X inactivation; in her sister and daughter with classic RS and in her hemizygous son, who died from congenital encephalopathy. This finding suggested that X-chromosome inactivation (XCI) pattern could be the major determinant of the phenotype in females. The severity of RS is believed to be a function of the percentage of cells with active, mutated MECP2 genes. MECP2 gene encodes a protein called MeCP2 that helps to orchestrate the “rests” that certain genes must take during the developmental symphony. If a defective MeCP2 protein is unable to “conduct” gene expression, then a neural chaos will result.MeCP2 is actually just a member of a family of methyl-binding proteins, all of which may help to regulate gene function. Mutations in any of these proteins or their interacting partners may be responsible for atypical RS, autism, severe neonatal encephalopathy, and non-syndromal mental retardation. The spectrum of phenotypes of MECP2 mutations is surprisingly wide with lethality to normality in the two extremes. (3) Even though the mutational types could have contributed to the phenotypes, some findings suggested that the X-chromosome inactivation (XCI) pattern may be the major determinant of the phenotype in females. We had reported MECP2 mutation in a cohort of Chinese girls with RS and autism (2000). (4, 5) We hope to explore the spectrum of phenotypes resulting from MECP2 mutations in the Chinese population. We hope to establish a systemic way of mutational analysis of the gene in RS and its possible variant including girls with autism or autistic features, developmental stagnancy or regression in girls with unknown etiology, and severe neonatal encephalopathy. XCI pattern will be examined in the family in which the mutation has been detected. We aim to study mutational analysis of the MECP2 gene in other related neurodevelopmental disorder with similar core autistic or neurological regression features, e.g. girls with autism or autistic features, developmental stagnancy or regression girls without unknown etiology, and newborn with unexplained severe encephalopathy and non-syndromal mental retardation. XCI pattern will be examined in family members if mutation is detected. Long term objective: We hope that prenatal test to detect RS families can be available in families with affected daughters (though the risk is < 1%). We hope to test for asymptomatic daughters in RTT families early on (prefebly in stage 1) (< 12 months) such that an early diagnosis can be made or refuted to alleviate parental anxiety. Objective: To detect MECP2 mutation in children with Autistic traits including Rett syndrome, atypical Rett Syndrome, Autism, unexplained mental retardation and infantile epileptic encephalopathy

Project Title:	In vitro study of the protective effects of calcium channel blocker or chemical chelators on metallic compound induced neurotoxicity
Investigator(s):	Wong VCN, Chen W, Chan GCF
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2007

Abstract:

1. To investigate the pro-apoptotic effect of excessive metallic compounds (i.e. iron, mercury & lead) on neural stem cells (NSC) and the possible apoptotic pathways involved. 2. To verify the hypothesis that calcium channel blocker or chemical chelators can prevent or minimize the toxic effects induced by these excessive metallic compounds on NSC.

Project Title:	Mutations of sodium channel and Gabanergic genes in Chinese children with Spectrum of Febrile Seizures:
Investigator(s):	Wong VCN
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	10/2008
Completion Date:	09/2009

Abstract:

Within the past 5 years, mutations in sodium channel genes (SCN1A, SCN1B, SCN 2A) and Gabanergic genes (GABRG2) have been detected in various febrile seizures and related epilepsy syndromes, both in children and in adults (Kearney, Plummer et al. 2001; Sugawara, Tsurubuchi et al. 2001; Sugawara, Mazaki-Miyazaki et al. 2002; Wallace, Scheffer et al. 2002; Fujiwara, Sugawara et al. 2003; Bergren, Chen et al. 2005; Kimura, Sugawara et al. 2005; Audenaert, Schwartz et al. 2006; Audenaert, Van Broeckhoven et al. 2006; Ito, Yamakawa et al. 2006; Jansen, Sadleir et al. 2006; Nakayama and Arinami 2006; Yamakawa 2006; Xu, Thomas et al. 2007). In Europe and North America, 2-5% of children experience febrile seizures, whereas this is higher (6-9%) in Japan. In Hong Kong, we had estimated that the prevalence of FS is 3% (Chung et al 2006). GEFS+: Generalized epilepsy with febrile seizure plus (GEFS+) is a clinical subset of febrile seizures, which often persist in children beyond 6 years of age. GEFS+ is an autosomal dominant epilepsy that displays various seizure phenotypes such as absences, myoclonic seizures, febrile seizures and atonic seizures (Kimura, Sugawara et al. 2005; Yamakawa 2006). SMEI: The most severe phenotype within the GEFS+ spectrum is severe myoclonic epilepsy in infancy (SMEI) or Dravet syndrome (Audenaert, Van Broeckhoven et al. 2006). SEMI is characterized by fever- induced partial and generalized seizures which usually begin in the first year of life. While the phenotype of GEFS+ is relatively benign, patients with SEMI show severe mental decline, slowed psychomotor development, ataxia and even develop life-threatening status epilepticus (Sugawara, Mazaki-Miyazaki et al. 2002; Jansen, Sadleir et al. 2006). Mutations of sodium channel genes (SCN1A) in SMEI In the study of Fujiwara (Fujiwara, Sugawara et al. 2003), de novo mutations of voltage-gated sodium channel alpha subunit, SCN1A have been identified in approximately 80% of Japanese patients with SMEI, suggesting that SCN1A mutation could be the major cause of SMEI. Mutations of Gabanergic genes (GABRG2) in SMEI In addition to SCN1A, an inherited mutation of gamma-2 subunit of the gamma-aminobutyric acid (GABRG2) was observed in a patient with SMEI in a family with GEFS+ (Fujiwara, Sugawara et al. 2003). Mutations of sodium channel genes (SCN1A) and Gabanergic genes (GABRG2) in GEFS+ SCN1A and GABRG2 mutations were also identified in patients with GEFS+ (Audenaert, Schwartz et al. 2006; Audenaert, Van Broeckhoven et al. 2006). While two-thirds of the SCN1A mutations in SMEI are truncations and frameshifts, most of the mutations identified in GEFS+ are missense mutations (Sugawara, Mazaki-Miyazaki et al. 2002; Yamakawa 2006). Mutations of sodium channel genes (SCN1B) in GEFS+ Moreover, several reports identified mutations in voltage-gated sodium channel beta subunit (SCN1B) in GEFS+ patients (Wallace, Scheffer et al. 2002; Xu, Thomas et al. 2007). Mutations of sodium channel genes (SCN2A) in GEFS+ Mutation in voltage-gated sodium channel alpha-II subunit (SCN2A) has also been proposed to cause severe seizure disorders (Kearney, Plummer et al. 2001; Sugawara, Tsurubuchi et al. 2001; Bergren, Chen et al. 2005). Therefore, specific genetic causes of GEFS+ and SEMI remain to be identified.

Project Title:	International and IX Ukrainian Congress of Child Neurology Neurohabilitation - Integration of Traditional Chinese Medicine and Western Medicine
Investigator(s):	Wong VCN
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	09/2009
Completion Date:	09/2009

Abstract:

N/A

List of Research Outputs

Baum L., Zhang C., Wong V.C.N., Ng P.W., Lui C.H.T., Sin N.C., Tomlinson B., Wong K.S. and Kwan P., Association of epilepsy with voltage gated sodium channel gene polymorphisms in Han Chinese, 63rd Annual Meeting of the American Epilepsy Society, Boston, USA, 4-8 December 2009.

Chan S.H.S., Mak W. and Wong V.C.N., A girl with atypical chronic inflammatory demyelinating polyneuropathy, 11^th International Child Neurology Congress, Cairo, Egypt, 2-7 May 2010. The International Journal of Child Neuropsychiatry (poster presentaion). 2010, 90.

Chan S.H.S., Mak W. and Wong V.C.N., A girl with atypical chronic inflammatory demyelinating polyneuropathy, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Chan S.H.S., Fung C.W., Yung A.W.Y., Lee S.L., Wong V.C.N., Dale R.C. and Vincent A.C., Anti-NMDA-R encephalitis - an encephalitis lerthargica-like illness, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Chan S.H.S., Wong V.C.N., Fung C.W., Dale R.C., Vincent A., Yung A.W.Y. and Lee S.L., Anti-NMDAR encephalitis - An encephalitis lethargica like illness, 11^th International Child Neurology Congress, Cairo, Egypt, 2-7 May 2010. The International Journal of Child Neuropsychiatry (poster presentaion). 2010, 184.

Chen W., Wong V.C.N., Yang M. and Chan G.C.F., Calcium Channel blockers can reduce iron-induced apoptosis in neuroal stem cells, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Chen W., Wong V.C.N. and Liu W.L., Double Blind Randomized Control Trial of Acupuncture for Autistic Spectrum Disorder, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Chen W., Liu W.L. and Wong V.C.N., Electroacupuncture for children with autism spectrum disorder: pilot study of 2 cases. , Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November, 2009.. 2009.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Siu S., Mak C.M., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitter assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD)(Diamond Prize). 2010.

Fung C.W., Siu S., Blau N., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November, 2009.. 2009.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Blau N., Siu S., Mak C., Tam S. and Wong V.C.N., A study of cerebrospinal fluid neurotransmitters assay in children with undiagnosed neurological diseases in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Fung C.W., Chung B.H.Y., Ng P., Zhao M., Yang W. and Wong V.C.N., Infantile Convulsion Choreoathetosis Syndrome in a Hong Kong Chinese Family, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Fung C.W., Poon G.W.K., Kwok A.M.K., Cheung P.T., Low L.C.K., Mak C., Tam S., Siu S. and Wong V.C.N., Spectrum of mitochondrial diseases in a tertiary referral centre in Hong Kong, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010.

Lam S.S., Li L., Chu V.L.Y. and Wong V.C.N., Pilot project of integratin of Chinese medicine (acupuncture) and western medicine for neurohabilitation of children with acquired brain injury - a study of 2 cases, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Ma Y.M., Liu T.K.T. and Wong V.C.N., Guillain-Barre syndrome in southern Chinese children: 32 year experience in Hong Kong. , Pediatrics International. 2010, 52: 13-9.

Mak C.M., Lam C.W., Siu T.S., Chan K.Y., Siu C.W.K., Yeung W.L., Hui J., Wong V.C.N., Low L.C.K., Ko C.H., Tam S. and Chan Y.W., Biochemical and molecular characterization of tyrosine hydroxylase deficiency in Hong Kong Chinese, Molecular Genetics and Metabolism. 2010, 99(4): 431-433.

Tso W.W.Y., Yung A.W.Y., Lun K.S., Yung T.C., Fan K. and Wong V.C.N., Posterior Reversible Encephalopathy Syndrome (PRES): Paediatric heart transplant with cyclosporine neurotoxicity, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Wong V.C.N., Acupuncture for Autistic Spectrum Disorder, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Wong V.C.N., Autism Spectrum Disorder 2009, 13th Asian Pacific Congress of Pediatrics and 3rd Asian Pacific Congress of Pediatric Nursing, Shanghai, China, 14-18 October 2009.

Wong V.C.N. and Chu V.L.Y., Autism spectrum disorder and traditional Chinese medicine (acupuncture). , In: In: Garralda E, & Raynaud, J-P. (Eds.), ed. , Increasing awareness of child and adolescent mental health. New York: Jason Aronson; 2010.. 2010.

Wong V.C.N., Chairperson, Plenary Lecture: Neurology II, 13th Asian Pacific Congress of Pediatrics and 3rd Asian Pacific Congress of Pediatric Nursing (Shanghai, China, 14-18 October 2009), 16 October 2009. 2009.

Wong V.C.N., Complementary & Alternative Medicine (CAM0 for Neurological?Neuro-Developmental and Neuro-Psychiatric Disorders in Children, IACAPAP and ASCAPAP congress in Beijing, 2-6 June, 2010.

Wong V.C.N., Conference Moderator in Discussion Session, International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD), Taipei, Taiwan, 26-28 March, 2010. 2010.

Wong V.C.N., Leonard H. and Ko L., Developmental and intellectual delay (pediatric). , In: Ebell MH, Ferenchick G, Smith M, Barry H, Slawson D, Shaughnessy A, Forsch R, Li S, Wilkes M, Usatine R, eds. Essential Evidence. John Wiley & Sons: Hoboken, NJ, 2009.. 2009.

Wong V.C.N., Editorial Board Member (Since 2001), Pediatric Neurology. 2010.

Wong V.C.N., Editorial Board Member (Since 2001), Pediatrics International. 2010.

Wong V.C.N., Editorial Board Member (Since 2002), Paediatric Rehabilitation. 2010.

Wong V.C.N., Editorial Board Member (Since 2003), Brain & Development. 2010.

Wong V.C.N., Editorial Board Member (Since 2003), Journal of Pediatric Neurology. 2010.

Wong V.C.N., Editorial Board Member (Since 2005), Current Pediatrics Reviews. 2010.

Wong V.C.N., Executive Board Member (2006-2010, 2010-2014), International Child Neurology Association. 2010.

Wong V.C.N., Hereditary Prosopagnosia (HPA) in Hong Kong. , 13th China Child Neurology Congress (CCNC), Zhengzhou City, Henan Province, China, 21-25 April, 2010.

Wong V.C.N., Hong Kong Delegate (1987-2013), Asian Oceanean Child Neurology Association. 2010.

Wong V.C.N., Member (Since 2009), "Guidelines Task Force" in Commission on Paediatrics, International Child Neurology Association. 2009.

Wong V.C.N., Member (since 2009), In: International Child Neurology Association, "Epilepsy-Autism Task Force" in Autism Speaks. 2009.

Wong V.C.N., Neurohabilitation - Integration of Traditional Chinese Medicine Western Medicine, International and IX Ukrainian Congress of Child Neurology, Kyiv, Ukraine, 9-12 September 2009.

Wong V.C.N., Neurohabilitation – Integration of Traditional Chinese Medicine and Western Medicine. , International and IX Ukrainian Congress of Child Neurology “Overview on the Nervous System Disorders in Children”, Kyiv, Ukraine, 9-12 September, 2009.. 2009.

Wong V.C.N., Li L., Lam S.S., Wong C.L. and Chu V.L.Y., Pilot project of integration of Chinese medicine (acupuncture) and western medicine for neurohabilitation of children with acquired brain injury - a study of 2 cases, 19th World Congress of Neurology, Bangkok, Thailand, 24-30 October 2009.

Wong V.C.N., President (2009-2011), Paediatric Neurological Association of Hong Kong. 2009.

Wong V.C.N., Sun J.G. and Yeung D.W.C., Randomized Control Trial of Using Tongue Acupuncture in Autism Spectrum Disorder Using PET Scan for Clinical Correlation, The Journal of Alternative and Complementary Medicine. 2010, 16(2): 1-12.

Wong V.C.N. and Kwan Q.K.L., Randomized Controlled Trial for Early Intervention for Autism: A Pilot Study of the Autism 1-2-3 Project, Journal of Autism & Developmental Disorders. 2010, 40(6): 677-688.

Wong V.C.N. and Sun J.G., Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture inAutism Spectrum Disorder, The Journal of Alternative and Complementary Medicine. 2010, 545-553.

Wong V.C.N., Reviewer (Since 1987), Brain & Development. 2010.

Wong V.C.N., Reviewer (Since 1987), Hong Kong Medical Journal. 2010.

Wong V.C.N., Reviewer (Since 1990), Clinical Drug Investigation. 2010.

Wong V.C.N., Reviewer (Since 1990), Hong Kong Journal of Paediatrics. 2010.

Wong V.C.N., Reviewer (Since 2000), Journal of Pediatric Neurology. 2010.

Wong V.C.N., Reviewer (Since 2000), Medical Progress. 2010.

Wong V.C.N., Reviewer (Since 2000), Pediatrics. 2010.

Wong V.C.N., Reviewer (Since 2003), BMJ Pediatrics. 2010.

Wong V.C.N., Reviewer (Since 2003), Child: Care, Health and Development. 2010.

Wong V.C.N., Reviewer (Since 2003), Developmental Medicine and Child Neurology. 2010.

Wong V.C.N., Reviewer (Since 2003), Epilepsia. 2010.

Wong V.C.N., Reviewer (Since 2003), European Journal of Paediatric Neurology. 2010.

Wong V.C.N., Reviewer (Since 2003), Journal of Paediatrics, Obstetrics & Gynaceology (JPOG). 2010.

Wong V.C.N., Reviewer (Since 2003), Medical Science Monitor. 2010.

Wong V.C.N., Reviewer (Since 2004), American Journal of Epidemiology. 2010.

Wong V.C.N., Reviewer (Since 2005), Lancet. 2010.

Wong V.C.N., Reviewer (Since 2005), New England Journal of Medicine. 2010.

Wong V.C.N., Reviewer (Since 2006), Archives of Pediatrics & Adolescent Medicine. 2010.

Wong V.C.N., Reviewer (Since 2007), Epileptic Disorders. 2010.

Wong V.C.N., Reviewer (Since 2007), Infection. 2010.

Wong V.C.N., Reviewer (Since 2007), Neuropediatrics. 2010.

Wong V.C.N., Reviewer (Since 2007), Pediatric Rehabilitation/Developmental Neurorehabilitation. 2010.

Wong V.C.N., Reviewer (Since 2007), The Lancet Neurology. 2010.

Wong V.C.N., Reviewer (Since 2007), The Open Pediatric Medical Journal. 2010.

Wong V.C.N., Reviewer (Since 2008), Archives of Physical Medicine and Rehabilitation. 2010.

Wong V.C.N., Reviewer (Since 2008), Autism Research. 2010.

Wong V.C.N., Reviewer (Since 2008), Indian Pediatrics. 2010.

Wong V.C.N., Reviewer (Since 2008), International Journal of Developmental Neuroscience. 2010.

Wong V.C.N., Reviewer (Since 2008), Journal of Autism and Developmental Disorders. 2010.

Wong V.C.N., Reviewer (Since 2008), Journal of Zhejiang University - SCIENCE "B". 2010.

Wong V.C.N., Reviewer (Since 2008), Neurology India. 2010.

Wong V.C.N., Reviewer (Since 2008), Yonsei Medical Journal. 2010.

Wong V.C.N., Reviewer (Since 2009), Libertas Academica. 2010.

Wong V.C.N., Reviewer (Since 2009), World Journal of Pediatrics. 2010.

Wong V.C.N., Reviewer (Since 2010), In: Clinical Neuropharmacology, Clinical Neuropharmacology. 2010.

Wong V.C.N., Reviewer (Since 2010), Evidence Bases Complementary and Alternative Medicine. 2010.

Wong V.C.N., Reviewer (Since 2010), Journal of Pediatric Epilepsy. 2010.

Wong V.C.N., Reviewer (Since 2010), Molecular Autism. 2010.

Wong V.C.N., Reviewer (since 2009), Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2009.

Wong V.C.N. and Yung A.W.Y., Risk factors associated with childhood medical intratability, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Wong V.C.N. and Chu V.L.Y., Role of Complementary & Alternative Medicine (CAM) Using Acupuncture for Autism Spectrum Disorder (ASD) (poster presentation) , International Meeting for Autism Research, IMFAR meeting, Philadelphia, USA, May 20-22, 2010.

Wu Y., Jin Z., Li K., Lu Z.L., Wong V.C.N., Han T.L., Zheng H., Caspi O., Liu G., Zeng Y.W. and Zou L.P., Functional Magnetic Resonance Imaging Activation of the Brian in Children : Real Acupoint Versus Sham Acupoint, Journal of Child Neurology. 2009, 25: 849-855.

Yung A.W.Y., Wong V.C.N., Khong P.L., Mak H.K.F., Hung K.N., Chan P.H., Ho W.Y. and Fan Y.W., Paediatric Epilepsy Surgery Program in Hong Kong - a single centre experience, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Researcher : Wong WHS

List of Research Outputs

Cheung E.W.Y., Wong W.H.S. and Cheung Y.F., Systematic review and meta-analysis of pulmonary valve replacement in children and adults after surgical repair of tetralogy of Fallot, The 6th Korea-Japan-China Pediatric Heart Forum, March 26-27, 2010, Seoul, Korea . 2010.

Cheung Y.F., Cheung E.W.Y. and Wong W.H.S., Systematic review and meta-analysis of pulmonary valve replacement in children and adults after surgical repair of tetralogy of Fallot, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association. Taipei, Taiwan, China 2010. . 2010.

Chiu S.S.S., Chan K.H., Chen H., Young B.W., Lim W., Wong W.H.S., Lau Y.L. and Peiris J.S.M., Virologically confirmed population-based burden of hospitalization caused by influenza A and B among children in Hong Kong, Clinical Infectious Diseases. 2009, 49: 1016-1021.

Ho M.H.K., Lee S.B.H., Wong W.H.S. and Lau Y.L., Peanut oil and peanut allergy, foes or folks?, Archives of Disease in Childhood [Epub in print]. 2010, 1-2.

Huen K.F., Low L.C.K., Cheung P.T., Wong G.W.K., But B.W.M., Kwan E.Y.W., Lam Y.Y., Lee C.Y., Wong L.M., Ng K.L., Cheng A.W.F., Tong C.T. and Wong W.H.S., An Update on the Epidemiology of Childhood Diabetes in Hong Kong , Hong Kong Journal of Paediatrics . 2009, 14: 252-259.

Lee P.P.W., Chan K.W., Wong W.H.S., Ho M.H.K., Lee T.L. and Lau Y.L., Primary Immunodeficiency Referral Network in Asia: Database Review 2001-2009, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 2010.

Wong C.M., Chiu S.S.S., Yang L., Wong T.W., Ma S., He J.F., Chen P., Chan K.P., Chan K.H., Wong W.H.S. and Peiris J.S.M., The burden of seasonal influenza in Hong Kong: A model-based approach with validation and comparison with other tropical/subtropical cities (poster presentation), MISMS Oceania Regional Meeting and Workshop, 15-19 March 2010, Melbourne. Melbourne, National Institutes of Health, 2010.

Yang W., Shen N., Ye D.Q., Liu Q., Qian X.X., Hirankarn N., Pan H.F., Mok C.C., Chan D.T.M., Wong R.W.S., Lee K.W., Wong S.N., Leung A.M.H., Li X.P., Avihingsanon Y., Wong C.M., Lee T.L., Ho M.H.K., Lee P.P.W., Chang Y.K., Li P.H., Li R., Zhang L., Wong W.H.S., Ng I.O.L., Lau W.C.S., Sham P.C., Lau Y.L. and Asian Lupus Genetics Consortium A.L.G.C., Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. , PLoS Genetics. 2010, 6: e1000841.

Researcher : Yang LH

Project Title:	Anti-inflammatory mechanisms of Ligusticum Chuangxiong
Investigator(s):	Yang LH, Lau ASY, Cheung BKW
Department:	Medical Faculty
Source(s) of Funding:	Small Project Funding
Start Date:	01/2009

Abstract:

Introduction: Cerebral ischemia (stroke) is a leading cause of death and long-term disability worldwide. It occurs when there is interruption of blood supply to the brain or when there is bleeding in the brain. Within minutes of reduced cerebral blood flow, brain cells begin to die. Two groups of therapeutic agents are currently being developed for the treatment of stroke: one for antiplatelet aggregation and the other for anticoagulation. These drugs can effectively prevent stroke from further deterioration. However, there are associated adverse effects including gastrointestinal irritation and severe bleeding. Therefore, alternative therapies for the treatment of early and intermediate stages of stroke are desirable. Although different mechanisms are involved in the pathogenesis of stroke, there are increasing evidences demonstrating that inflammation partly accounts for its progression and complications (Barone and Feuerstein, 1999; Samson et al., 2005). Some studies have suggested that inflammation of the brain is due to reduction of cerebral blood flow leading to energy depletion as well as necrotic neuronal death. These events trigger immune responses which ultimately lead to activation of immune cells including macrophages. In turn, these activated macrophages secrete small intercellular signaling molecules known as proinflammatory cytokines including interferon-γ (IFN-γ), interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha (TNF-α). Among these cytokines, TNF-α is considered as the key mediator that is implicated in the pathogenesis of cerebral ischemia (Barone and Feuerstein, 1999; del Zoppo et al., 2000). Several studies have shown that there is a rapid upregulation of TNF-α mRNA and protein in activated microglia and macrophages after focal stroke (Buttini et al., 1996). Also, in an in vivo study, Siren (1992) showed that hypertensive rats with propensity for stroke have higher levels of TNF-α production in the brain than that of the normotensive rats. The involvement of mitogen-activated protein (MAP) kinase cascades and transcription factors NF-kB in TNF-α expression has been demonstrated (Trede et al., 1995). Therefore, these results implicated that development of therapies directed towards the inhibition of TNF-α production and/or deactivation of the MAP kinase signaling pathways may help to ameliorate the severity of cerebral ischemia. The use of medicinal plants or their crude extracts in the prevention and/or treatment of diseases has been traditionally practiced worldwide. Recently, the use of traditional Chinese medicines (TCM) is gaining popularity and it is important to investigate the scientific basis of their therapeutic actions. In our previous studies in collaboration with Prof. Robert Ko of HKUST, Prof. A. Lau’s group showed that extracts from a post-stroke rehabilitation (PSR) formula demonstrated anti-inflammatory effects. This PSR formula includes eight traditional Chinese herbs. Among them, the extracts of Ligusticum Chuangxiong (LCX) exhibited a very significant suppressive effect on TNF-α production. In light of these preliminary results, we hypothesize that specific chemical constituents of LCX modulate the inflammatory responses via regulation of specific signaling kinase activities and transcription factors, which lead to reduced cytokine expressions in immune cells. Objectives: First, we will find out the most suitable method for extracting and fractionating LCX extracts until a definable list of compounds with anti-inflammatory effect is obtained. Second, we will investigate the anti-inflammatory mechanisms of LCX in immune cells such as macrophages. Our Specific aims are: Aim 1. To determine the most suitable extraction method of LCX Aim 2. To fractionate and isolate anti-inflammatory compounds from LCX Aim 3. To investigate the mechanisms of anti-inflammatory effects of compounds isolated from LCX in primary human blood macrophages (PBM) References: 1. Barone FC, Feuerstein GZ. (1999). Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19:819–834. 2. Buttini M, Appel K, Sauater A, Gebicke-Haerter P-J, Boddeke HWGM. (1996). Expression of tumour necrosis factor alpha after focal cerebral ischemia in the rat. Neuroscience 71:1−16. 3. del Zoppo G, Ginis I, Hallenbeck JM, Iadecola C, Wang X, Feuerstein GZ. (2000). Inflammation and stroke: putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia. Brain Pathol 10:95–112. 4. Siren AL, Heldman E, Doron D, Lysko PG, Yue T-L, Liu T, Feuerstein GZ, Hallenbeck J. (1992). Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Stroke 23:1643−1651. 5. Samson Y, Lapergue B, Hosseini H. (2005). Inflammation and ischaemic stroke: current status and future perspectives. Rev Neurol 161:1177–1182. 6. Trede NS, Tsytsykova AV, Chatila T, Goldfeld AE, Geha RS. (1995). Transcriptional activation of the human TNF-alpha promoter by superantigen in human monocytic cells: Role of NF-kappaB. J Immunol 155:902–908.

Project Title:	The 8th Consortium for Globalization of Chinese Medicine Meeting Anti-inflammatory mechanisms of Black Cohosh on human primary blood macrophages via its downregulation of signal transduction and transcription factor activation
Investigator(s):	Yang LH
Department:	Medical Faculty
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	08/2009
Completion Date:	08/2009

Abstract:

N/A

List of Research Outputs

Lau A.S.Y., Yang L.H. and Law H.Y., USA Patent Application #61/219,073: Materials and Methods for Prevention and Treatment of Viral Infections. , Type: Provisional, Priority date for IP: 12/30/2009. (Assignee/owner: HKU). 2009.

Lau A.S.Y., Yang L.H., Or C.T. and Law H.Y., USA Patent Application #61/263,517: Novel Therapeutic Methods for Treating Inflammation and Immune System Disorders., Type: Provisional, Author from HKU and Priority date for IP: 11/23/2009. (Assignee/owner: HKU). 2009.

Lee D.C.W., Yang L.H., Chik S.C.C., Li J., Rong J., Chan G.C.F. and Lau A.S.Y., Immunomodualtory effect of Panax ginseng on human promonocytic U937 cells, Journal of Translational Medicine. 2009, 7: 34-40.

Or C.T., Yang L.H., Cheung B.K.W. and Lau A.S.Y., Mechanisms of Ligusticum chuanxiong (LCX) extracts in the suppression of proinflammatory cytokine expression in blood macrophages, 9^th World Congress on Inflammation 2009, Tokyo, Japan, 8 July. 2009.

Yang L.H., Chik S.C.C., Li C.B., Cheung B.K.W. and Lau A.S.Y., Identification of the bioactive constituent and its mechanisms of action in mediating the anti-inflammatory effects of black cohosh and related Cimicifuga species on human primary blood macrophages., Journal of Medical Chemistry. 2009, 52(21): 6707-6715.

Researcher : Yang M

Project Title:	Protective effect of thrombopoietin on iron-induced cardiomyopathy
Investigator(s):	Yang M
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Children's Thalassaemia Foundation - General Awards
Start Date:	07/2007

Abstract:

To investigate the pro-apoptotic effect of iron overload in cardiomyocytes and this effect may be mediated by caspase dependent pathway; to confirm the hypothesis that TPO has a protective effect on iron-induced apoptosis in cardiomyocytes via the activation of Akt signaling pathway.

Project Title:	The effect of melatonin in the treatment of thrombocytopenia
Investigator(s):	Yang M
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Queen Mary Hospital Charitable Trust - Training and Research Assistance Scheme
Start Date:	01/2008

Abstract:

To investigate the mitogenic effect of MLT on in-vitro megakaryocytopoiesis and proplatelet formation; to analyze the effect of MLT on thrombopoiesis in a thrombocytopenic model; to analyze the role of G-protein receptors on megakaryocytopoiesis and proplatelet formation in a G i2-deficient mice.

Project Title:	The protective effects of thrombopoietin and amlodipine on iron overload-induced human mesenchymal stem cell damage: its impact on iron overload related osteopenia & osteoporosis
Investigator(s):	Yang M, Chan GCF, Cheung YF, Liu C
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Children's Thalassaemia Foundation - General Awards
Start Date:	01/2009

Abstract:

(1) To investigate the pro-apoptotic effect of iron-overload in bone marrow mesenchymal stem cells and this effect may be mediated by caspase dependent pathway. (2) To test the hypothesis that haematopoietic growth factor TPO may have a protective effect on iron-induced apoptosis in bone marrow mesenchymal stem cells via the activation of TPO receptor c-mpl and AKT/ERK signaling pathway. (3) To test the hypothesis that calcium channel blocker amlodipine may prevent iron-overload in bone marrow mesenchymal stem cells via inhibiting iron uptake into the cells. (4) To identify the genes and proteins involved in human MSC under either iron-induced toxicity or preventive effect of TPO or amlodipine.

Project Title:	ISSCR 7th Annual Meeting Serotonin, a new growth factor for bone marrow stem cells and megakaryocytes
Investigator(s):	Yang M
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	07/2009
Completion Date:	07/2009

Abstract:

N/A

List of Research Outputs

Chen J., Chan G.C.F. and Yang M., Human cytomegalovirus inhibited megakaryocytic differentiation, maturation and induced apoptosis in vitro., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Chen J., Chan G.C.F., Ye J., He Z.X., Wang Q.W., Pan S.N., Li X.F., Deng R.X. and Yang M., Human cytomegalovirus inhibited megakaryocytic differentiation, maturation and induced apoptosis in vitro, Blood [Abstract in 2009 American Society of Hematology], 22 November 2009. 114: 2413.

Chen M., Chan S., Yang M., Chan G.C.F. and Cheung Y.F., Travel Award (supervisor of MMed Sc student; Chen Meipian): Iron overload induced apoptosis in HL-1 cardiomyocytes via mitochondria-mediated caspase-3 dependent pathways, The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association. Taipei, Taiwan, PR China 2010. . 2010.

Chen W., Wong V.C.N., Yang M. and Chan G.C.F., Calcium Channel blockers can reduce iron-induced apoptosis in neuroal stem cells, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Dai Y., Qiao L., Chan K.W., Yang M., Ye J., Zhang R., Ma J., Zou B., Lam S.C., Wang J., Pang R.W.C., Tan V.P.Y., Lan H.Y. and Wong B.C.Y., Adenovirus-mediated down-regulationof X-linked inhibitor of apoptosis protein inhibits colon cancer, Molecular Cancer Therapeutics. 2009, 8(9): 2762-2770.

Deng R., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui Buxue Tang (DBT) and its major components on hematopoiesis., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Deng R.X., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui and its component Ferulic Acid on haematopoiesis and platelet production, Blood [Abstract in 2009 American Society of Hematology], 20 November 2009. 114.

Ye J., Chan G.C.F. and Yang M., Effect of recombinant PDGF-BB on thrombopoiesis in a mouse model., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Yu J., Chan G.C.F. and Yang M., Platelet-derived growth factor enhances platelet recovery in a radiation-induced thrombocytopenic mouse model and reduces apoptosis in megakaryocytes via its receptors and PI3- k/Akt pathway, Haematologica. 2010, 95: 1745-1753.

Researcher : Yang W

Project Title:	Association of Gene Copy Number Variations (CNV) in the FCGR locus with Systemic Lupus Erythematosus (SLE)
Investigator(s):	Yang W, Lau YL
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2008
Completion Date:	07/2010

Abstract:

In this study, we propose to examine the roles of low affinity IgG Fc Receptor (FCGR) genes in the genomic locus 1q23 as risk factors for Systemic lupus erythematosus (SLE) in the Chinese population. We are going to test two related hypothesis that were not tested in previous studies. First, we will test whether gene Copy Number Variations (CNVs) of the related genes in this locus play any roles in the susceptibility to SLE. Second, we will test whether impairment of functional balance of activating receptors (FCGRIIa and FCGRIIIa) and inhibitory receptors (FCGRIIb) in this locus confers disease risk to SLE. We will examine some known missense mutations in the related low affinity FCGRs in this region, as well as CNVs for these genes, and analyze the combinations of the changes (haplotypes) that could tilt the balance of the activation and inhibitory functions by FCGRs, for their roles in conferring increased disease risk to SLE. SLE is a complex autoimmune disease of multi-system organ involvement, characterized by various autoantibody production and damage to multiple tissues. It is a disease with significant morbidity and mortality. Similar to many other autoimmune diseases, SLE demonstrates a complex pattern of inheritance that is consistent with the involvement of multiple susceptibility genes as well as environmental factors[1, 2]. SLE has long been associated with defects in immune complex clearance [3] and SLE lesions are invariably associated with immune complex deposition [4]. Impaired handling of antigen-antibody complexes in SLE leads to their deposition in tissue and to organ damage, particularly glomerulonephritis[1]. FCGRs mediate immune responses following binding to complexed IgG and play an important role in the clearance of immune complexes. Allelic variation of FCGR alters the functional capacities of phagocytes and provides a mechanism for heritable differences in susceptibility to immune complex-mediated injury [5, 6]. Three main classes of receptors binding IgG are known: FCGRI, FCGRII, and FCGRIII. The two classes of low affinity receptors, FCGRII and FCGRIII, are encoded by five distinct genes in humans, located in chromosome 1q23, a region repeatedly found to be linked to SLE in genome scans using multiplex families of SLE from different ethnicities [7-9]. These five genes are derived from divergent evolution and are located in a region of less than 200KB, with tremendous sequence similarity to each other (Figure 1). The Two general classes of FCGRs include the activation receptors characterized by the presence of a cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM) sequence associated with the receptor (including FCGRIIa and IIIa, see Figure 1), and the inhibitory receptor (mainly FCGRIIb, see Figure 1), characterized by the presence of an immunoreceptor tyrosine-based inhibitory motif (ITIM) sequence. The paring of activation and inhibition is necessary to initiate, amplify, and then terminate immune responses. Perturbations in either component result in pathological responses. Because activation and inhibitory receptors bind IgG with comparable affinity and specificity, coengagement of both signaling pathways sets thresholds for and ultimately determining the magnitude of effector cell responses[10]. Therefore we hypothesize that the collective changes in this locus play key roles in SLE susceptibility and need to be examined and analyzed in the same cohort. Copy number variations (CNV) is common in regions containing immune-related genes [11] and the potential impact of this on polygenic autoimmunity was demonstrated by the association between FCGRIIIb and complement component C4 CNV and SLE [12-14]. Our own work demonstrates that in a family with FCGRIIIb-deficiency, and in the normal population, that CNV correlates with protein expression, immune complex uptake, and neutrophil adhesion to immunoglobulin-coated surfaces [15]. This would be expected to result in impaired immune complex clearance, a feature of SLE, explaining the association between low FCGRIIIb CN and SLE. Previous studies on the involvement of FCGR gene polymorphisms in SLE produced controversial results [16, 17, 18 ]. They showed circumstantial evidence for the involvement of the genes in this locus in SLE susceptibility but with tremendous variations in the conclusions and often conflicting results both between and within populations. Although many factors, such as subpopulation stratification, small sample size, and linkage disequilibrium pattern in this region may explain the different findings in these studies, we hypothesize that there is a balance in the functions of the activation and inhibitory receptors encoded in this locus, and it is the tilting of the balance in these gene functions that are important to the susceptibility to the disease. Therefore, we will examine the missense mutations in the genes in this locus, together with CNVs for these genes, in a Hong Kong SLE cohort containing close to 1, 000 SLE patients and matched controls, and analyze the collective changes (or haplotypes) in this locus of five closely related genes and to identify the haplotypes that are important to SLE susceptibility. 1. Croker, J.A. and R.P. Kimberly, Trends Immunol, 2005. 26(11): p. 580-6. 2. Rigby, R.J., et al., Rheumatology (Oxford), 2006. 45(9): p. 1062-7. 3. Davies, K.A., et al., J Clin Invest, 1992. 90(5): p. 2075-83. 4. Kozora, E., et al., Arthritis Rheum, 1996. 39(12): p. 2035-45. 5. Ravetch, J.V. and S. Bolland, Annu Rev Immunol, 2001. 19: p. 275-90. 6. Takai, T., Nat Rev Immunol, 2002. 2(8): p. 580-92. 7. Moser, K.L., et al., Proc Natl Acad Sci U S A, 1998. 95(25): p. 14869-74. 8. Shai, R., et al., Hum Mol Genet, 1999. 8(4): p. 639-44. 9. Tsao, B.P., et al., Arthritis Rheum, 2002. 46(11): p. 2928-36. 10. Ravetch, J.V. and L.L. Lanier, Science, 2000. 290(5489): p. 84-9. 11. Redon, R., et al., Nature, 2006. 444(7118): p. 444-54. 12. Fanciulli, M., et al., Nat Genet, 2007. 39(6): p. 721-3. 13. Mamtani, M., et al., Ann Rheum Dis, 2007. 14. Yang, Y., et al., Am J Hum Genet, 2007. 80(6): p. 1037-54. 15. Willcocks, L., et al., Nat Genet, 2007. in press. 16. Clatworthy, M.R., et al., Proc Natl Acad Sci U S A, 2007. 104(17): p. 7169-74. 17. Kyogoku, C., et al., Arthritis Rheum, 2004. 50(2): p. 671-3. 18. Siriboonrit, U., et al., Tissue Antigens, 2003. 61(5): p. 374-83.

Project Title:	Genetic variations in Jak2 gene and their roles in Systemic Lupus Erythematosus (SLE) susceptibility in different populations
Investigator(s):	Yang W
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2009
Completion Date:	11/2010

Abstract:

SLE is an autoimmune disease characterized by auto-antibody production and multi-organ damage. It is a disease with strong genetic involvement. The disease risk for siblings of affected is 20-30 times higher than in the general population, and monozygotic twin concordance rate is over 20(1,2). There is also a strong population difference to the disease. Asians and Africans have higher disease prevalence and more severe manifestations(3,4). Understanding the susceptibility genes for the disease will surely help us better understand the disease mechanisms, improve clinical interventions and allow personalized treatment of the disease. Although candidate gene approaches, linkage analysis based on multiplex families, and animal models improved our understanding, it is the genome-wide association studies(GWAS) that are revealing many novel susceptibility genes with an incredibly rapid pace(5,6). The problem is that most of the GWAS were based on Caucasians, and other populations are seriously underrepresented. Our own work replicating the Caucasian findings revealed both similarities and striking differences (manuscript under review), pointing to the promises that there could be susceptibility genes only affecting Asians. We recently genotyped 200 SLE samples using Illumina-610-Quad-beadchip. With the help of Professors Pak Sham and Irene Ng providing us with control data, and by accessing HapMap-data in public databases, we were able to perform preliminary analysis on the whole genome level. Based on the analysis, we have chosen 50 SNPs that showed significant differences on all three comparisons for replication, one of them is in Jak2 gene, a locus that was not reported in previous GWAS in Caucasians. Using TaqMan technology and the rest of our samples, we were able to confirm that rs10758669 in Jak2 is indeed associated with SLE in Hong Kong Chinese(Table 1). This gives us reason to believe that this is potentially a population-specific susceptibility gene for SLE. We are proposing here to do detailed genetic and functional characterization of this gene using sample collections from different populations, both Asians and others. Table 1. Replication of Genome-wide finding by additional samples on SNP rs10758669 in Jak2: Experiment SLE samples (N) Control samples (N) SLE MAF Control MAF Chi^2 P value Chip_result 194 390 42.70% 33.00% 7.38 6.58E-03 Replication 1 192 192 39.40% 34.80% 1.60 2.00E-01 Replication 2 384 96 42.80% 34.90% 4.00 4.55E-02 Total 770 678 41.94% 34.13% 18.73 1.51E-05 *MAF: minor allele frequency. In this study, we are going to do the following: 1. Identifying the SNP(s)/Haplotypes in this locus that are independently contributing to the disease association. The chip data and the replication data indicate that the association of rs10758669 is real (P = 1.5E-5) although more samples will still be examined on this site. The chip data also indicates that there could be other genetic variants associated with the disease independently since the SNPs showed significant P value in the gene have little linkage disequilibrium (LD) with rs10758669, as analyzed by HapMap data for Chinese/Japanese. We will further analyze the HapMap data and choose tag SNPs for this gene, and SNPs showed moderate LD with rs10758669 beyond the Jak2 gene for further genotyping using Sequenom in our sample collection of 1000 cases and 1500 controls. Analysis using Haploview on HapMap data indicate that we would have to genotype around 25 SNPs in and around this gene to have coverage with r2 value of 0.8 or above. This part of the work will serve to identify the most significant SNPs/Haplotypes associated with the disease in Hong Kong Chinese. We expect that eventually we could identify 2-3 SNPs that may have independent contribution towards disease susceptibility. Analysis will also be done on sub-phenotype stratification and disease outcomes. 2. Examining the identified SNP(s) in objective 1 in other cohorts in China and Thailand, and non-Asian populations. To establish the association of Jak2 gene with SLE in Asian populations, it is essential to examine the identified SNPs in objective 1 in independently-collected cohorts. We have established collaboration with SLE researchers in China and Thailand, namely Dr. Ye Dongqing in AnHui Medical University, Dr. Shen Nan in Shanghai Jiaotong University, and Dr. Nattiya Hirankarn in Chulalongkorn University, Thailand, who have established SLE cohorts and have agreed to take part in this work. Once the findings are confirmed in Asian populations, we will further ask the question whether the association is Asian population-specific. Dr. Gary Gilkeson in the Medical University of South Carolina, who have the largest SLE collection of African Americans and Gullah Samples (an isolated African American population), as well as Caucasian samples, also agreed to replicate findings in our Asian populations. 3. Preliminary functional characterization of the genetic variants conferring disease susceptibility: Jak2 gene is an important non-receptor protein tyrosine kinase that plays important role in cytokine responses. It works upstream of signal transducer and activator of transcription (STAT) proteins, of which STAT4 has been found to be associated with SLE as well as disease subphenotypes (e.g., lupus nephritis and ds-DNA_autoantibody production) in our own study and others. Establishing the functional connection of the genetic variants with the disease is important for a better understanding of the disease and the gene, although only preliminary characterization can be performed in the scope of this application. Since rs10758669 is located 3kb upstream of Jak2 gene, we predict that it may affect the expression level of Jak2 in lymphocytes and dendritic cells. Barring for the possibility that other genetic variants show more significant association with the disease, we would propose to examine the relationship of this genetic variation with Jac2 gene expression level in lymphocytes. Functional characterizations will also be performed should different genetic variants show independent contribution towards disease susceptibility and the nature of the SNPs pointing to other functional relationships, being either protein coding change, gene expression or alternative splicing. Both wet lab experiments and bioinformatics in silico analysis will be performed, with the latter a strength in our laboratory with students with bioinformatics and computer science background.

Project Title:	Mapping Susceptibility Genes for Systemic Lupus Erythematosus (SLE) through a Genome-Wide Association Study
Investigator(s):	Yang W, Lau YL, Sham PC
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	09/2009

Abstract:

1) To identify multiple novel genetic risk factors contributing to SLE susceptibility through genome-wide association study and replication using an overall total of 1,920 SLE patients 2,560 matched healthy controls; 2) To identify genetic factors involved in certain subphenotypes of SLE for which we have enough power, such as renal involvement, and potentially to use genetic information to guide clinical intervention and patient care; 3) To distinguish the susceptibility genes affecting different ethnicities from those only affecting Asian populations by testing our findings in populations of other origins.

Project Title:	The 59th Annual Meeting of the American society of Human Genetics GWAS of systemic lupus erythematosus on a Chinese population in Hong Kong
Investigator(s):	Yang W
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2009
Completion Date:	10/2009

Abstract:

N/A

Project Title:	Non-HLA susceptibility genes associated with systemic lupus erythematosus in the HLA locus - A GWAS follow-up study
Investigator(s):	Yang W
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2010

Abstract:

1. To examine the SNPs in the HLA locus in detail (following up on findings from GWAS on SLE), to identify non-HLA genes independently associated with SLE susceptibility. 2. Further examination of identified genes for functional variants associated with the disease. 3. To examine their association with subphenotypes of the disease.

List of Research Outputs

Fung C.W., Chung B.H.Y., Ng P., Zhao M., Yang W. and Wong V.C.N., Infantile Convulsion Choreoathetosis Syndrome in a Hong Kong Chinese Family, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Lee P.P.W., Chen T.X., Jiang L.P., Chan K.W., Yang W., Lee B.W., Chiang W.C., Chen X.Y., Fok S.F.S., Lee T.L., Ho M.H.K., Yang X.Q. and Lau Y.L., Clinical Characteristics and Genotype-phenotype Correlation in 62 patients with X-linked Agammaglobulinemia, Journal of Clinical Immunology. 2010, 30: 121-131.

Wang L., Wang Z. and Yang W., Linked region detection using high-density SNP genotype data via the minimum recombinant model of pedigree haplotype inference, BMC Bioinformatics. 2009, 10: 216.

Willcocks L.C., Carr E.J., Niederer H.A., Rayner T.F., Williams T.N., Yang W., Scott J.A.G., Urban B.C., Peshu N., Vyse T.J., Lau Y.L., Lyons P.A. and Smith K.G.C., A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus, Proceedings of the National Academy of Sciences. 2010, 107(17): 7881-7885.

Yang W., Shen N., Ye D.Q., Liu Q., Qian X.X., Hirankarn N., Pan H.F., Mok C.C., Chan D.T.M., Wong R.W.S., Lee K.W., Wong S.N., Leung A.M.H., Li X.P., Avihingsanon Y., Wong C.M., Lee T.L., Ho M.H.K., Lee P.P.W., Chang Y.K., Li P.H., Li R., Zhang L., Wong W.H.S., Ng I.O.L., Lau W.C.S., Sham P.C., Lau Y.L. and Asian Lupus Genetics Consortium A.L.G.C., Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. , PLoS Genetics. 2010, 6: e1000841.

Yang W., Ying D. and Lau Y.L., In-depth cDNA Library Sequencing Provides Quantitative Gene Expression Profiling in Cancer Biomarker Discovery, Genomics Proteomics Bioinformatics. 2009, 7: 1-12.

Yu F., Chen M., Kuo L., Huang P. and Yang W., Bayesian Hierarchical Modeling and Selection of Differentially Expressed Genes for the EST Data, Biometrics [EPub ahead of print]. 2010, 1-9.

Researcher : Ye J

List of Research Outputs

Chen J., Chan G.C.F., Ye J., He Z.X., Wang Q.W., Pan S.N., Li X.F., Deng R.X. and Yang M., Human cytomegalovirus inhibited megakaryocytic differentiation, maturation and induced apoptosis in vitro, Blood [Abstract in 2009 American Society of Hematology], 22 November 2009. 114: 2413.

Dai Y., Qiao L., Chan K.W., Yang M., Ye J., Zhang R., Ma J., Zou B., Lam S.C., Wang J., Pang R.W.C., Tan V.P.Y., Lan H.Y. and Wong B.C.Y., Adenovirus-mediated down-regulationof X-linked inhibitor of apoptosis protein inhibits colon cancer, Molecular Cancer Therapeutics. 2009, 8(9): 2762-2770.

Deng R., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui Buxue Tang (DBT) and its major components on hematopoiesis., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Deng R.X., Ye J., Liu C., Chan G.C.F., Chen J., Shen J. and Yang M., Effects of Danggui and its component Ferulic Acid on haematopoiesis and platelet production, Blood [Abstract in 2009 American Society of Hematology], 20 November 2009. 114.

Ye J., Chan G.C.F. and Yang M., Effect of recombinant PDGF-BB on thrombopoiesis in a mouse model., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. Dec 2-3. 2009.

Researcher : Yeung WL

List of Research Outputs

Mak C.M., Lam C.W., Siu T.S., Chan K.Y., Siu C.W.K., Yeung W.L., Hui J., Wong V.C.N., Low L.C.K., Ko C.H., Tam S. and Chan Y.W., Biochemical and molecular characterization of tyrosine hydroxylase deficiency in Hong Kong Chinese, Molecular Genetics and Metabolism. 2010, 99(4): 431-433.

Researcher : Yick LW

Project Title:	Defining the roles of epidermal growth factor (EGF) in the regulation of chondrocyte differentiation and endochondral bone formation
Investigator(s):	Yick LW, Chan SY
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To understand the role of EGF in chondrocyte differentiation using our 'knock-in mice' with targeted expression of EGF in prehypertrophic chondrocytes.

Researcher : Yim HCH

List of Research Outputs

Au K.Y., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV TAT modulation of IFN-g induced expression of autophagy-associated genes in primary human blood macrophages., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV Tat modulation of IFN- γ-induction of autophagy-associated genes in primary human blood macrophages., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. December 2-3. 2009.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., HIV Tat modulation of IFN-γ-induced expression of autophagy-associated genes in primary human blood macrophages., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine 2009;46(1-2)PP1-095]. 2009.

Au K.Y., Li C.B., Yim H.C.H., Fang J.W. and Lau A.S.Y., Travel Award, 2010 Annual General Meeting and Scientific Meeting, Hong Kong Society for Immunology, Hong Kong, April 17, 2010 . 2010.

Cheung B.K.W., Yim H.C.H., Lee N.C.M. and Lau A.S.Y., A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1, BMC Immunology 2009 (17 Dec);10:64. 2009, 64: 1-10.

Cheung B.K.W., Yim H.C.H. and Lau A.S.Y., Positive role of mitogen-activated protein kinase phosphatase-1 in regulating the anti-mycobacterial immune response., Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society & International Society for Interferon and Cytokine Research, (Tri-Society Conf of SLB, ICS & ISICR) Lisbon, Portugal 17-21 October 2009 [Cytokine-the official journal of International Cytokine Society 2009;46(1-2)PP1-071]. 2009.

Fang J.W., Yim H.C.H. and Lau A.S.Y., Interleukin-17A differentially modulates mycobacterial-induction of cytokines in human blood macrophage., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.

Fang J.W., Li C.B., Yim H.C.H. and Lau A.S.Y., Modulation of mycobacterium bovis (BCG)-induced cytokine response by IL-17., 9th World Congress on Inflammation 2009, Tokyo, Japan, July 8,. 2009.

Li C.B., Cheng M., Yim H.C.H., Lee D.C.W. and Lau A.S.Y., Mechanisms underlying HIV-1 suppression of IFN-γ signaling pathways: A role for transactivator Tat in the induction of SOCS-2 in primary human blood monocytes., Tri-Society Annual Conference, Lisbon, Portugal, October 18-21. 2009.

Yim H.C.H. and Lau A.S.Y., HIV-1 Tat dysregulation of lipopolysaccharide-induced cytokine responses: microbial interactions in HIV infection, AIDS. 2009, 23: 1473-84.

Yim H.C.H., Cheung B.K.W. and Lau A.S.Y., Mitogen-activated protein kinase phosphatase-1 positively regulates the anti-mycobacterial immune responses (oral presentation)., 14th Research Postgraduate Symposium, LKS Faculty of Medicine, The University of Hong Kong. December 2-3,. 2009.

Researcher : Ying D

List of Research Outputs

Yang W., Ying D. and Lau Y.L., In-depth cDNA Library Sequencing Provides Quantitative Gene Expression Profiling in Cancer Biomarker Discovery, Genomics Proteomics Bioinformatics. 2009, 7: 1-12.

Researcher : Yip PMC

List of Research Outputs

Liao S., Liu Y., Siu D.C.W., Zhang Y., Lai K.W.H., Au K.W., Lee Y.K., Chan Y.C., Yip P.M.C., Wu E.X., Lau C.P., Wu Y., Li R.A. and Tse H.F., Pro-arrhythmic Risk of Embryonic Stem Cell-Derived Cardiomyocytes Transplantation in Infarcted Myocardium. Heart Rhythm. , 2010.

Researcher : Yu J

List of Research Outputs

Yu J., Chan G.C.F. and Yang M., Platelet-derived growth factor enhances platelet recovery in a radiation-induced thrombocytopenic mouse model and reduces apoptosis in megakaryocytes via its receptors and PI3- k/Akt pathway, Haematologica. 2010, 95: 1745-1753.

Researcher : Yung AWY

List of Research Outputs

Chan S.H.S., Fung C.W., Yung A.W.Y., Lee S.L., Wong V.C.N., Dale R.C. and Vincent A.C., Anti-NMDA-R encephalitis - an encephalitis lerthargica-like illness, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Chan S.H.S., Wong V.C.N., Fung C.W., Dale R.C., Vincent A., Yung A.W.Y. and Lee S.L., Anti-NMDAR encephalitis - An encephalitis lethargica like illness, 11^th International Child Neurology Congress, Cairo, Egypt, 2-7 May 2010. The International Journal of Child Neuropsychiatry (poster presentaion). 2010, 184.

Tso W.W.Y., Yung A.W.Y., Lun K.S., Yung T.C., Fan K. and Wong V.C.N., Posterior Reversible Encephalopathy Syndrome (PRES): Paediatric heart transplant with cyclosporine neurotoxicity, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Wong V.C.N. and Yung A.W.Y., Risk factors associated with childhood medical intratability, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Yung A.W.Y., Wong V.C.N., Khong P.L., Mak H.K.F., Hung K.N., Chan P.H., Ho W.Y. and Fan Y.W., Paediatric Epilepsy Surgery Program in Hong Kong - a single centre experience, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Researcher : Yung TC

List of Research Outputs

Hong W., Yung T.C., Lun K.S., Wong S.J. and Cheung Y.F., Impact of right ventricular pacing on three-dimensional global left ventricular dyssynchrony in children and young adults with congenital and acquired heart block associated with congenital heart disease , The American Journal of Cardiology. 2009, 104: 700-706.

Hong W., Yung T.C., Lun K.S., Wong S.J. and Cheung Y.F., Impact of temporary interruption of right ventricular pacing for heart block on left ventricular function and dyssynchrony. , Pacing and Clinical Electrophysiology. 2010, 33: 41-48.

Ko L.Y., Chau A.K.T., Yung T.C., Cheung Y.F. and Lun K.S., Retrospective Review on Anomalous Left Coronary Artery from Pulmonary Artery , Hong Kong Journal of Paediatrics . 2010, 15: 12-18.

Koh C., Lee P.P.W., Yung T.C., Lun K.S. and Cheung Y.F., Left ventricular noncompaction in children, Cogenital Heart Disease. 2009, 4: 288-294.

Lun K.S., Fan K., Yung T.C., Wong K.T., Cheung Y.F., Chau A.K.T. and Cheng L.C., Experience of pediatric heart transplantation in Hong Kong, International Congress of Cardiology, Hong Kong, 26-28 February 2010.

Lun K.S., Fan K., Wong C.F., Yung T.C., Chow P.C., Wong K.T., Cheung Y.F., Chow W.H., Chau A.K.T., Chiu S.W. and Cheng L.C., Outcome of thoracic organ transplantation for adults with congenital heart disease, 18^th Annual Scientific Congress, Hong Kong College of Cardiology, Hong Kong, 14-16 May 2010.

Poon G.W.K., Kwok A.M.K., Cheung P.T., Yung T.C., Ng Y.K., Tsoi N.S., Wong K.Y. and Low L.C.K., Variable Response to Enzyme Replacement Therapy in Two Chinese Children with Infantile-onset Pompe Disease in Hong Kong , Hong Kong Journal of Paediatrics. 2009, 14: 243-251.

Tso W.W.Y., Yung A.W.Y., Lun K.S., Yung T.C., Fan K. and Wong V.C.N., Posterior Reversible Encephalopathy Syndrome (PRES): Paediatric heart transplant with cyclosporine neurotoxicity, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009.

Researcher : Zhang L

List of Research Outputs

Yang W., Shen N., Ye D.Q., Liu Q., Qian X.X., Hirankarn N., Pan H.F., Mok C.C., Chan D.T.M., Wong R.W.S., Lee K.W., Wong S.N., Leung A.M.H., Li X.P., Avihingsanon Y., Wong C.M., Lee T.L., Ho M.H.K., Lee P.P.W., Chang Y.K., Li P.H., Li R., Zhang L., Wong W.H.S., Ng I.O.L., Lau W.C.S., Sham P.C., Lau Y.L. and Asian Lupus Genetics Consortium A.L.G.C., Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. , PLoS Genetics. 2010, 6: e1000841.

Researcher : Zhang Y

List of Research Outputs

Mao H., Tu W., Qin G., Lau H.K.W., Chan P.L., Liu Y., Lam K.T., Zhang Y., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, Journal of Virology. 2009, 83: 9215-9222.

Researcher : Zhao M

List of Research Outputs

Fung C.W., Chung B.H.Y., Ng P., Zhao M., Yang W. and Wong V.C.N., Infantile Convulsion Choreoathetosis Syndrome in a Hong Kong Chinese Family, ASHG 2009 Annual Meeting, Hawaii, Honolulu, 20-24 October 2009.

Researcher : Zheng J

List of Research Outputs

Liu Y., Zheng J., Lau Y.L. and Tu W., Intrinsic IFN-gamma-T-bet pathway mediates the Generation of Th1-like regulatory T cells induced by CD40-activated B cells, FOCIS meeting. 2010.

Mao H., Tu W., Qin G., Law H.K., Sia S.F., Chan P.L., Liu Y., Lam K.T., Zheng J., Peiris J.S.M. and Lau Y.L., Influenza virus directly infects human natural killer cells and induces cell apoptosis, J Virol. 2009, 83(18): 9215-22.

Mao H., Tu W., Liu Y., Qin G., Zheng J., Chan P.L., Lam K.T., Peiris J.S.M. and Lau Y.L., Inhibition of human natural killer cell activity by influenza virions and hemagglutinin, J Virol. 2010, 84(9): 4148-57.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded Human Gammadelta T Cells Display Potent Cytotoxicities Towards Human and Avian Influenza Virus-infected Monocyte-derived Macrophages, clinical immunology. 2009, 131: s91-s92.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded gammadelta T cells display potent cytotoxicity against human and avian influenza virus-infected monocyte-derived macrophages, Journal of Infectious Diseases. 2009, 200: 858-865.

Qin G., Mao H., Zheng J., Sia S.F., Liu Y., Chan P.L., Lam K.T., Peiris J.S.M., Lau Y.L. and Tu W., Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses, J Infect Dis. 2009, 200(6): 858-65.

Tu W., Mao H., Zheng J., Liu Y., Chiu S.S.S., Qin G., Chan P.L., Lam K.T., Guan J., Zhang L., Guan Y., Yuen K.Y., Peiris J.S.M. and Lau Y.L., Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-react against 2009 Pandemic H1N1 Influenza Virus, Journal of Virology. 2010, 84(13): 6527-6535.

Tu W., Zheng J., Liu Y. and Lau Y.L., Stimulatory or tolerohenic role of CD40-activated B cells depends on the strength of the activation to T cells, blood. U.S.A., 2009, 114: 747-748.

Zheng J., Liu Y., Lau Y.L. and Tu W., CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4(+) regulatory T cells, Cell Mol Immunol. 2010, 7(1): 44-50.

Zheng J., Liu Y., Lau Y.L. and Tu W., CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4+ regulatory T cells, Cellular & Molecular Immunology. 2010, 7: 44-50.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., lewis D.B., Lau Y.L. and Tu W., Efficient Induction and Expansion of Human Alloantigen-Specific CD8 Regulatory T Cells from Naive Precursors by CD40-Activated B Cells. , Journal of Immunology. U.S.A., 2009, 2009 Aug 14.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lam K.T., Lewis D.B., Lau Y.L. and Tu W., Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells, J Immunol. 2009, 183(6): 3742-50.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H.W., Lewis D.B., Lau Y.L. and Tu W., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, Clinical Immunology. 2009, 131: S163-S163.

Zheng J., Liu Y., Qin G., Chan P.L., Mao H., Lewis D.B. and Lau Y.L., Large-scale Induction and Expansion of a Novel Human Alloantigen-specific CD8 Regulatory T Cells, clinical immunology. 2009.

Researcher : Zheng J

List of Research Outputs

Liu Y., Zheng J., Lau Y.L. and Tu W., Intrinsic IFN-gamma-T-bet pathway mediates the Generation of Th1-like regulatory T cells induced by CD40-activated B cells, FOCIS meeting. 2010.

Tu W., Zheng J., Liu Y. and Lau Y.L., Stimulatory or tolerohenic role of CD40-activated B cells depends on the strength of the activation to T cells, blood. U.S.A., 2009, 114: 747-748.

Zheng J., Liu Y., Lau Y.L. and Tu W., CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4(+) regulatory T cells, Cell Mol Immunol. 2010, 7(1): 44-50.

Researcher : Zhou J

List of Research Outputs

Chong W.P., Zhou J., Law H.K.W., Tu W. and Lau Y.L., Natural killer cells become tolerogenic after interaction with apoptotic cells, European Journal of Immunology. 2010, 40: 1-10.

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