Medical Faculty

MEDICAL FACULTY

Researcher : Hui EC

Project Title:	A survey of viewpoints regarding medical decision-making capacity of adolescents in Hong Kong
Investigator(s):	Hui EC, Kuan HY, Chiu S.Y.
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding for New Staff
Start Date:	09/2004

Abstract:

To investigate healthcare providers' attitudes and perspectives regarding AP and their capacity for and right to MDM; to investigate the attitudes and perspectives of parents of both well and sick adolescents regarding AP and their capacity for and right to MDM; to investigate the attitudes and perspectives of well and sick adolescents and young adults in age groups between 12 to 21 regarding capacity for and right to MDM; to make a comparison of the attitudes and perspectives of healthcare providers, parents and adolescents regarding AP and their capacity for and right to MDM.

Project Title:	Promotion of the reflection, dialogue and teaching of ethical issues related to the development and uses of biotechnologies among students and faculty members of health-related sciences at the University of Hong Kong
Investigator(s):	Hui EC
Department:	Medical Faculty
Source(s) of Funding:	Teaching Development Grants
Start Date:	03/2005

Abstract:

(1) To enhance in the HKU campus an awareness of the ethical issues related to the rapid advances of bio-technology and to promote among students and faculty members moral dialogues and discourses of the impacts of bio-technoogy on the Hong Kong society, socially, medically, legally, economically and environmentally. (2) To develop skills in clinical ethics analysis based on a Case-Based Learning approach for medical, nursing and Chinese Medicine students in the Faculty of Medicine as well as dental students from the Faculty of Dentistry. (3) To train and support faculty members in biological, physical, and social sciences, law, bio-engineering, environmental students, psychology, medicine, nursing, dentistry, and Chinese Medicine to engage in ethical reflections and to stimulate students to think ethically as they teach in their respective disciplines of learning. (4) To provide a "venue", a university website on ethics and biotechnology, to encourage a campus-wide dialogue, discussion and debate of bioethical issues, as well as dissemination of information.

Project Title:	Ethical decision-making and the potential use of advance directives by Hong Kong Chinese patients with meta-static and/or recurrent cancer: a prospective study
Investigator(s):	Hui EC, Chua DTT, Liu R., Yau CC
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2005

Abstract:

The overall goal of this study is to develop an ethical framework for the management of cancer patients in Hong Kong that takes into consideration the Chinese cultural background that informs and shapes patients' values, beliefs, preferences, goals and decisions.

List of Research Outputs

Hui E.C., Doctors as Fiduciaries: a Legal Construct of the Patient-physician Relationship, Hong Kong Medical Journal. 2005, 11: 420-422.

Hui E.C., Ethical Principles and Oversight Policies for Human Stem Cells (Part I), Medicine and Philosophy. 2006, 27: 1-5.

Hui E.C., Ethical Principles and Oversight Policies for Human Stem Cells (Part II), Medicine and Philosophy. 2006, 27: 20-23.

Hui E.C., Ethics of Stem Cell Transplant for Patients with Spinal Cord Injuries, Inivted Speaker of the Investigators' Meeting on Spinal Cord Injury for the ChinaSCINet. 15&16 October 2005. The University of Hong Kong Spinal Cord Injury Fund.. 2005.

Hui E.C., Perceptions of Adolescent Medical Decision-Making by Healthy Secondary School Teenagers and Their Parents in Hong Kong, Poster Presentation - 3rd Congress of Asian Medical Education Association. Seoul, Korea, 23-26 October 2005.. 2005.

Hui E.C., The Contractual Model of the Patient-Physician Relationship and the Demise of Medical Professionalism, Hong Kong Medical Journal. Hong Kong, Hong Kong Academy of Medicine Press, 2005, 11 (5): 67-69.

Hui E.C., The Development of a New Curriculum in Medical Ethics for Undergraduate Students in the University of Hong Kong, Oral Presentation - 3rd Congress of Asian Medical Education Association. Seoul, Korea, 23-26 October 2005.. 2005.

Hui E.C., The Doctor as Fuduciaries: Do Doctors Have the Right Not to Treat, Poiesis & Prax. 2005, 3: 256-276.

Hui E.C., The Patient-surgeon Relationship. Part I: Its Professional Nature and Moral Implications, Asian Journal Oral Maxillofac Surg. 2005, 17: 151-156.

Hui E.C., The Patient-surgeon Relationship. Part II: Its Professional Nature and Moral Implications, Asian J Oral Maxillofac Surg. 2005, 17: 210-216.

Researcher : Lam SK

Project Title:	Chemoprevention of gastric cancer by intervention with Helicobacter pylori and cyclooxygenase pathway
Investigator(s):	Lam SK, Wong BCY, Xu G.W.
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2001

Abstract:

To assess if the combination of treatment of Helicobacter pylori infection and use of specific cyclooxygenase-2 inhibitors in asymptomatic individuals can reduce the incidence of gastric cancer in a high risk area over a five to ten year period; to assess if the combination of treatment of Helicobacter pylori infection and use of specific cyclooxygenase-2 inhibitors will lead to progression or regression of various precancerous gastric conditions including gastric atrophy, intestinal metaplasia and dysplasia over a three year period; to assess the long term sequelae of Helicobacter pylori eradication and use of specific cyclooxygenase-2 inhibitors histologically, including changes in cell proliferation, apoptosis and oncogene expressions.

Project Title:	Biotech Company in the Faculty of Medicine, The University of Hong Kong
Investigator(s):	Lam SK
Department:	Medicine
Source(s) of Funding:	The University of Hong Kong Foundation Seed Grant
Start Date:	07/2003

Abstract:

To enable the Faculty of Medicine of The University of Hong Kong to establish itself as the regional centre of excellence in the provision of complete solutions to industry from laboratory research services to clinical trials, setting standards and quality benchmarks comparable to the best international practices for other similar centres in the region to follow.

Project Title:	Treatment of gastrointestinal cancer by targeting survivin using adeno-associated virus gene delivery system
Investigator(s):	Lam SK, Wong BCY, Lin MC
Department:	Medical Faculty
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2004

Abstract:

To elucidate the molecular mechanisms of survivin in tumor angiogenesis, to will investigater the effect of overexpression of survivin on the migration and capillary tuber-like networks of endothelial cells, expression of angiogenic factors in gastrointestinal cancer cells and angiogenesis in Chorioallantoic membrane angiogenesis (CAM) model and nude mice xenograft; to establish a novel gene therapy for gastrointestinal cancer by targeting survivin gene with adeno-associated virus vector. We will further study the therapeutic effect of rAAV-mediated survivin mutant on gastrointestinal cancer in vivo and evaluate long-term effect and safety of the rAAV virus.

Project Title:	The prevalence of Obstructive Sleep Apnea Syndrome (OSAS) in patients with gastro-oesophageal reflux disease (GERD) and the effects of proton pump inhibitor therapy on OSAS and quality of sleep in Hong Kong Chinese
Investigator(s):	Lam SK, Wong RWM, Ip MSM
Department:	Medical Faculty
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To study the prevalence of Obstructive Sleep Apnea Syndrome (OSAS) in Chinese patients with gastro-oesophageal reflux disease (GERD) and the effects of proton pump inhibitor therapy on OSAS and quality of sleep in patients with GERD.

Project Title:	Treatment of gastrointestinal cancer by targeting survivin using adeno-associated virus gene delivery system
Investigator(s):	Lam SK
Department:	Medical Faculty
Source(s) of Funding:	Merit Award for RGC CERG Funded Projects
Start Date:	01/2005

Abstract:

N/A

Project Title:	Characterization of the role of FHL2 in the induction of apoptosis and therapy of GI cancers
Investigator(s):	Lam SK
Department:	Medical Faculty
Source(s) of Funding:	Incentive Award for RGC CERG Fundable But Not Funded Projects
Start Date:	07/2005
Completion Date:	06/2006

Abstract:

N/A

List of Research Outputs

Lee A.M., Lam S.K., Lau S.M. and Tang L.C.H., Prevalence and risk factors of antenatal anxiety and depression among Chinese pregnant women, Paper presented at the Conference on the Quality of Life Research in Asia (May 19-21, 2006). Hong Kong, 2006.

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:	Seroepidemiological prevalence survey of SARS-associated coronavirus antibody in children residing in Amoy Garden compared to a control group in southern district
Investigator(s):	Lau YL, Peiris JSM, Chiu SSS, Lam TH
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Health and Health Services Research Fund - Full Grants
Start Date:	05/2004

Abstract:

To define the seropositive rate of SARS-associated coronavirus (CV) infection among children who are household contacts or community contacts of SARS cases; to ascertain the full clinical spectrum of SARS-associated CV infection among chldren in Amoy Garden.

Project Title:	Interferon-gamma gene polymorphism in systemic lupus erythematosus and rheumatoid arthritis
Investigator(s):	Lau YL
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004
Completion Date:	10/2005

Abstract:

To study the association of IFN-γ gene polymorphism (+874 A/T) with SLE and RA (case-control study); to investigate the association of this polymorphism with the clinical manifestation in patients with SLE and RA.

Project Title:	Joint Course on Molecular Medicine under the Joint Centre for Advanced Study
Investigator(s):	Lau YL
Department:	Medical Faculty
Source(s) of Funding:	Other Funding Scheme
Start Date:	07/2005

Abstract:

To carry out a joint course on molecular medicine under the Joint Centre for Advanced Study.

Project Title:	The role of dentritic cells in SARS coronavirus infection
Investigator(s):	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:	08/2005

Abstract:

Despite the SARS epidemic being controlled by case isolation, neither an effective treatment nor an efficacious vaccine is available. Our study will shed lights on the pathogenesis and the immune evasion of SARS-CoV and the knowledge gained may facilitate the development of new treatment protocols and vaccines for SARS.

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:	Immune response of cord blood macrophages and dendritic cells to the 1997 and 2004 strains of avian influenza viruses
Investigator(s):	Lau YL, Peiris JSM
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2005

Abstract:

(1) To determine the host response against human/avian viruses infection. In particular, we will focus on: host immune responses; mechanism of lymphopenia;evolution of H5N1; (2) to campare the cytokine/chemokine expression in antigen presenting cell infected by different influenza viruses; (3) to determine the expression of death receptor ligands in influenza infected APCs and subsequent effect on T cell priming and polarisation.

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:	Immune response of cord blood macrophages and dendritic cells to the 1997 and 2004 strains of avian influenza viruses
Investigator(s):	Lau YL
Department:	Paediatrics & Adolescent Med
Source(s) of Funding:	Merit Award for RGC CERG Funded Projects
Start Date:	09/2005

Abstract:

N/A

List of Research Outputs

Researcher : Li G

Project Title:	The Neuroprotective Effect of Coenzyme Q10 in AD mice model
Investigator(s):	Li G, Yang ES, Yang YiHong, Jack Jr. Clifford
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2006

Abstract:

Alzheimer's disease (AD) and ischemic cerebrovascular disease are two main causes of dementia in elderly people. Recent basic and clinical investigations demonstrate that AD and vascular dementia (VaD), traditionally considered two independent neurological disorders, may interact in an additive manner. In clinical studies, the presence of ischemic lesions enhances the cognitive deficits in patients with AD pathology. Mutations in the genes of beta-amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) cause familial AD. In transgenic mice with overexpressed APP, susceptibility to ischemic brain damage caused by middle cerebral artery occlusion (MCAO) is increased. In AD patients, the extent of AD pathology is increased if ischemic stroke coexists. Elderly subjects are more likely to have been demented in life if both AD pathology and ischemic cerebrovascular disease are present at autopsy than if either is pathology is found in isolation. Several studies suggest a possible role of increased oxidative stress and impairment of mitochondrial energy metabolism in the pathogenesis of both AD and stroke. A number of investigators have identified a deficiency in the complex VI, cytochrome c oxidase (COX) of the mitochondrial electron transport chain in AD patients and a reduced activity of complexes I and III in ischemic conditions. Coenzyme Q10 (CoQ10) is an essential biological cofactor produced endogenously in the body and provided in the food chain. As the electron acceptor for mitochondrial complexes I and II, it has an essential role in cellular energy production as an electron and proton carrier. Complex I or II dysfunction are found in neurological disorders such as Parkinson’s disease and Huntington disease. Shults et al. reported a correlation between mitochondrial CoQ10 level and the biological activity of complexes I - IV Parkinson’s disease patients who were administered the highest dose of CoQ10 showed the greatest clinical benefit. Oral CoQ10 supplementation increases brain mitochondrial concentrations and exerts neuroprotective effects. A neuroprotective effect of CoQ10 has been found in various animal models of stroke and this has been attributed to its role as a potent antioxidant and an oxygen derived free radical scavenger. This finding has not been universally replicated, however, as Li and his colleagues found that immediate treatment with CoQ10 via intraperitoneal injection did not prevent neuronal injuries following global and focal ischemia. Mitochondrial abnormalities have been found in human AD patients, and there are a few reports about the therapeutic effect of CoQ10 in AD patients. Results have been mixed however, for example, de Bustos et al. investigated serum levels of CoQ10 in patients with AD and found no relationship with the risk of AD and vascular dementia. CoQ10 has been shown to have a neuroprotective effect in other neurodegenerative diseases, such as Parkinson’s and Huntington’s diseases. In this study, we address the effects of CoQ10 on AD and cerebral ischemia using volume magnetic resonance imaging (MRI) in transgenic animal models. APP/PS1, APP and PS1 transgenic mice with ischemic stroke will be treated with high-dose CoQ10 for 28 days, and then their brain specimens will be examined by MRI to investigate the neuroprotective effects of CoQ10, compared to the non-treated counterparts. Transgenic rather than wild type mice will be employed in order to amplify the destructive effects of stroke in the experimental animals.

List of Research Outputs

Li G., Chan Q.C.C., Ehman R.L., Rossman P.J., Cao G., Li R. and Yang E.S., Shear waves Imaging Induced by Moving Needle. , The 5th National MRI Academic Congress. Oct. 15-18, 2004, Nanjing, China.. 2005.

Li G., Cheung R.T.F., Wong K.K., Ma Q.Y. and Yang E.S., A Functional MRI Study Comparing Brain Activation Between Word Generation and Electrical Stimulation of Language-implicated Acupoints. The Chinese Academy of Sciences. , The International Symposium on Cognitive Neuroscience. 14-18 August 2002 Qing Dao, China.. 2005.

Li G., Cheung R.T.F. and Yang E.S., An Fmri Study Of Senorimotor Deficit-related Acupoints Stroke Patients With Persistent Motor Deficits , Annual Meeting Press Book as a lay-language summary. The 34th Annual Meeting of Neuroscience. October 23-27, 2004 in San Diego, CA, USA.. 2005.

Li G., Jack Jr. C.R. and Yang E.S., An fMRI study of sensory deficit-implicated acupoints in sensory stroke patients., JMRI. 2006.

Li G., Tang A.M.Y., Jing G.G. and Yang E.S., Brain Activation Induced By Acupoint Stimulation In The Yin Meridian: Fmri Study. , Neurobiological Correlates of Acupuncture. Nov. 17-18, 2005, Bethesda, USA.. 2005.

Li G., Brain Activations on Functional Magnetic Resonance Imaging during Acupuncture and/or Physiological Tasks in Healthy Volunteers and Stable Stroke Patients., The 2nd Great China MR Research User Meeting – fMRI. Trader Hotel, August 21, 2004, Beijing, China.. 2005.

Li G., Zou L.Y., Cao C.M. and Yang E.S., Coenzyme Q10 Protects SHSY5Y Neuronal Cells From Beta Amyloid Toxicity And Oxygen-glucose Deprivation By Inhibiting The Opening Of The Mitochondrial Permeability Transition Pore., Biofactors / Invited Paper. 2005.

Li G., Cheung R.T.F., Gao J.H., Lee T.M.C., Tan L.H., Fox P., Jack Jr C.R. and Yang E.S., Cognitive Processing In Chinese Literate And Illiterate Subjects: An fMRI Study , In: Peter Fox, Hum Brain Mapp . 2005, 27: 144-152.

Li G., Innovation For Acupoint Research: Magnetic Resonance Elastography With A Needle Driver. , Neurobiological Correlates of Acupuncture. Nov. 17-18, 2005, Bethesda, USA.. 2005.

Li G., Peh W.C.G. and Yuen P.W., MR-surgical Correlation of the Volume of Tongue Carcinoma. , Advanced Body Imaging, Singapore Radiological Society 9th Annual Scientific Meeting 2000, Singapore.. 2006.

Li G., Neuroprotective Effects Of Coenzyme Q10 In Aged Mice: Volume Mri Study. , The 12th Annual Meeting of Chinese Society of Radiology. Sept. 19-23, 2005. Beijing, China.. 2005.

Li G., Zou L.Y., Jack Jr. C.R., Yang Y.H. and Yang E.S., Neuroprotective effect of Coenzyme Q10 on Ischemic Hemisphere in aged Mice with Mutations in the Amyloid Precursor Protein., In: Paul D. Coleman, Neurobiology of Aging. 2006.

Li G., Ng M.C., Wong K.K., Luk K.D.K. and Yang E.S., Proton Density-weighted Spinal Fmri Induced By Acupuncture Stimulation At 0.2t. , In: John Gore, Magnetic Resonance Imaging / Invited Paper. 2005, 23: 998-999.

Li G., The Neuropretictive Effect Of Coenzyme Q10 In Aging Mice And Shsy5y Neuronal Cells. , International Day for Alzheimer’s Disease. September 21, 2005. Beijing, China. . 2005.

Li G., The Neuroprotective Effect Of Coenzyme Q10 In Aging Mice And Shsy5y Neuronal Cells., International Alzheimer’s Disease And Related Disease Conference. August 18-22, 2005. Shang Hai, China.. 2005.

Li G., The scholarship for 4-year (Oct. 1, 2001 to Sept. 31, 2005) PhD study in The University of Hong Kong., The University of Hong Kong. 2005.

Li G., Wong K.K., Liu S.R., Huang L., Cao G., Shen G.X., Yang E.S. and Ma Q.Y., Use of Functional MRI to Evaluate Correlation Between Acuponts and the Somatic Sensory Cortex and Occipital Lobe Activities. , The First fMRI Technique and Application Investigation Meeting 2000, Beijing, China.. 2005.

Ng M.C., Wong K.K.K., Li G., Lai S., Yang E.S., Hu Y. and Luk K.D.K., Proton-density-weighted spinal fMRI with sensorimotor stimulation at 0.2 T, Neuroimage. 2006, 29: 995-999.

Ng M.C., Wong K.K., Li G., Lai S., Yang E.S., Hu Y. and Luk K.D.K., Proton Density-weighted Spinal Fmri With Sensorimotor Stimulation At 0.2t. , Neuroimage (accepted On 3rd Aug 2005.).. 2005.

Son J.G., Li G., Liu S.R., Huang L., Ma Q.Y. and Yang E.S., Tongue acupuncture significantly improves recovery in patients with chronic ischemic stroke., Journal of Alternative and Complementary Medicine. 2006.

Researcher : Li GR

Project Title:	Volume-sensitive chloride current and cell volume regulation in human atrial myocytes
Investigator(s):	Li GR, Lau CP, Chiu SW, Tse HF
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2001

Abstract:

To determine the intracellular signaling pathways that regulate I_Cl.vol and cell volume in human atrium; to determine whether I_Cl.vol is persistently activated in atrial myocytes from patients with dilated atrial cardiomyopathy.

Project Title:	Ionic channels of mesenchymal stem cells from bone marrow and cell proliferation
Investigator(s):	Li GR, Lau CP, Chung SSM, Tse HF
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2003
Completion Date:	07/2006

Abstract:

To analyze the molecular identities of IK_DR, I_KCa, and I_Na in MSCs from rat bone marrow with semi-quantitative reverse transcript-polymeterase chain reaction (RT-PCR) and patch clamp techniques; to test the hypothesis that the three types of channels (IK_DR, I_KCa and I_Na) are involved in the proliferation of rat MSCs by determining cell proliferation in the absence and presence of channel blockers and modulators.

Project Title:	Ionic channels of mesenchymal stem cells from bone marrow and cell proliferation
Investigator(s):	Li GR, Lau CP, Chung SSM, Tse HF
Department:	Medicine
Source(s) of Funding:	Merit Award for RGC CERG Funded Projects
Start Date:	12/2003
Completion Date:	11/2005

Abstract:

N/A

Project Title:	Modulation of cloned human cardiac potassium channel by protein tyrosine kinase
Investigator(s):	Li GR
Department:	Medical Faculty
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004
Completion Date:	10/2005

Abstract:

To clarify specific PTK pathway that is involved in the modulation of I_Ks channels.

Project Title:	Ion channels of preadipocytes and cell proliferation and differentiation
Investigator(s):	Li GR
Department:	Medical Faculty
Source(s) of Funding:	Incentive Award for RGC CERG Fundable But Not Funded Projects
Start Date:	07/2005
Completion Date:	06/2006

Abstract:

N/A

Project Title:	Studies on Ion Channels in Human Pre-adipocytes
Investigator(s):	Li GR, Lau CP
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2006

Abstract:

Ion channels play an important role in the physiological activities of many types of cells. In excitable cells, activation of ion channels generates action potentials and participates in excitation-contraction (muscles), excitation-secretion (glands), and impulse conduction (nerve and muscles), as well as repolarizing cell membrane potential. In proliferative cells, ion channels are found to be required for cell proliferation. Recent studies have demonstrated that several K channels, eg. inward rectifier K channels (IKir), delayed rectifier K channels (IKDR), ATP-sensitive K channel (IKATP), are involved in the cell cycling of lymphocytes, neuronal glial cells (e.g. astrocytes), epithelial cells, and cancer cells. Blockade of IKDR is believed to inhibit cell proliferation, whereas inhibition of IKIR promotes proliferation in rat spinal cord astrocytes. In addition, volume-sensitive chloride current (ICl.vol) is involved in the proliferation of several types of cells including vascular smooth muscle and endothelial cells, cancer cells etc. These studies indicate an important relationship between ion channels and cell proliferation. There has been a dramatic increase in the incidence of obesity resulting from an excess of white adipose tissue. Obesity is a prevalent health hazard in industrial countries, and is closely associated with the occurrence of type 2 diabetes and cardiovascular disease. Preadipocytes are the origin of fat cells of white adipose tissue. For the past two decades, in vitro systems have been extensively used to study adipocyte differentiation with preadipocytes. Although significant progress has been made in the dissection of the molecular and cellular events taking place during the transition from undifferentiated preadipocytes into mature round fat cells, control of adipocyte differentiation is not completely understood, especially ion channels and thire physiological roles in proliferation/differentiation have not been studied. The present proposal was to study ion channel expression and thire molecular identidies in human pre-adipocytes commercially obtained from CellSicence using whole-cell patch clamp and RT-PCR techniques, and to provide the experimental data for obtaining external RGC grant to further study whether/how ion channels are involved in proliferation/differentiation in human pre-adipocytes.

List of Research Outputs

Deng X., Lau C.P. and Li G.R., Cell-cycling dependent expression of potassium channels of rat mesenchymal stem cells from bone marrow., Journal of Hong Kong College Cardiology/The 9th Institute of Cardiovascular Science and Medicine & the 5th Scientific Conference on Cardiovascular Science Across the Strait. 2005, 13: 99-OP14.

Deng X., Sun H., Lau C.P. and Li G.R., Modulation of voltage-gated delayed rectifier potassium channels by EGFR-mediated kinase and relation to cell proliferation in mesenchymal stem cells from rat bone marrow, 11th Medical Research Conference, The University of Hong Kong/Queen Mary Hospital . 2006.

Li G.R., Deng X., Sun H., Chung S.S.M., Tse H.F. and Lau C.P., Ion channels in mesenchymal stem cells from rat bone marrow. , Stem Cells. 2006, 24: 1519-1528.

Li G.R., Ion channels in mesenchymal stem cells--their role in cell proliferation, Tongji Medical College, Huazhong University of Science and Technology. 2006, Invited lecture.

Li G.R., Liu H. and Lau C.P., Modulation of cardiac voltage-gated sodium current by the interplay of protein tyrosine kinase and phosphatases, Biophyscal Journal. 2006, 90: 435a-436a.

Li G.R., Signaling control of voltage-gated cardiac sodium channel current, Journal of Hong Kong College Cardiology/The 9th Institute of Cardiovascular Science and Medicine & the 5th Scientific Conference on Cardiovascular Science Across the Strait.. 2005, 13:93-IL10.

Li G.R., Signaling control of voltage-gated cardiac sodium channels current, The 9th Institute of Cardiovascular Science and Medicine & the 5th Scientific Conference on Cardiovascular Science Across the Strait, Conventional center, Hong Kong. 2005.

Li G.R., Voltage-Gated Cardiac Sodium Channels and Intracellular Signals, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2005.

Liu H., Jin M.W., Xiang J.Z., Huang Y., Chiu S.W., Lau C.P. and Li G.R., Effects of raloxifene on action potential, transient outward and ultra-rapid delayed rectifier potassium current in human atrial myocytes., Journal of Hong Kong College Cardiology/The 9th Institute of Cardiovascular Science and Medicine & the 5th Scientific Conference on Cardiovascular Science Across the Strait. 2005, 13:111-OP60.

Tao R., Lau C.P. and Li G.R., Functional ion channel expression in mouse bone marrow derived mesenchymal stem cells, Journal of Hong Kong College Cardiology/The 9th Institute of Cardiovascular Science and Medicine & the 5th Scientific Conference on Cardiovascular Science Across the Strait. 2005, 13:120-OP94.

Tao R., Lau C.P. and Li G.R., InsP3 receptor-mediated calcium oscillation regulates proliferation and differentiation of human mesenchymal stem cells from bone marrow, 11th Medical Research Conference, The University of Hong Kong/Queen Mary Hospital. 2006.

Tao R., Lau C.P. and Li G.R., Ion channels in mouse bone marrow derived mesenchymal stem cells, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

Tian M., Dong M., Chiu S.W., Lau C.P. and Li G.R., Effects of the antifungal antibiotic clotrimazole on human cardiac repolarization potassium currents. , British Journal of Pharmacology. 2006, 147: 289-297.

Wu K.K., Li G.R., Wong H.P.S., Hui K.C., Tai K.K., Lam K.Y., Shin V.Y., Ye Y., Li P., Yang Y., Luo J.C. and Cho C.H., Involvement of K(v)1.1 and Na(v)1.5 in proliferation of gastric epithelial cells, Journal of Cellular Physiology. 2006, 207: 437-444.

Xiao G., Zhou J., Wang G., Cao C., Li G.R. and Wong T.M., In vitro electrophysiologic effects of morphine in rabbit ventricular myocytes, Anesthesiology. 2005, 103: 280-286.

Zhang D., Lau C.P. and Li G.R., A depolarization-induced transient outward component in inward-rectifier potassium current is regulated by intracellular Mg2+ and spermine. , Journal of Hong Kong College Cardiology/The 9th Institute of Cardiovascular Science and Medicine & the 5th Scientific Conference on Cardiovascular Science Across the Strait. 2005, 13:130-OP130.

Zhang D., Lau C.P. and Li G.R., A depolirization-activated transient outward current is contributed by recombinant human cardiac Kir2.1 channels expressed in HEK 293 cells , 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

Zhang D., Lau C.P. and Li G.R., Regulation of human cardiac inwardly-rectifying Kir2.1 channels by tyrosine kinase phosphorylation, 11th Medical Research Conference, The University of Hong Kong/Queen Mary Hospital. 2006.

Researcher : Liu C

Project Title:	Systematic Determination and Compilation of DNA Barcodes for Medicinal Plants Used In Traditional Chinese Medicines
Investigator(s):	Liu C
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2006

Abstract:

During the past decades, interest in Traditional Chinese Medicine (TCM) has grown worldwide. Among the many barriers for TCM to enter the mainstream medicines is the inconsistent quality of TCMs. This complicating factor has hindered the research, development and testing of TCMs. As a result, recent guideline from the US Food and Drug Administration has outlined the required quality control measures (www.fda.gov/cder/guidance/4592fnl.htm) for botanical raw materials (that is, fresh or processed part of a single species of plant or a fresh or processed alga or macroscopic fungus), botanical drug substances (that is, materials derived from one or more plants, algae, or macroscopic fungi by certain processes.) and botanical drug products (that is, a finished, labeled product that contains vegetable matter processed from one or many botanical substance). Among all these quality control requirements, the first step is to make sure that the correct botanical species have been used in the formulation. Unfortunately, there is no universal standard species determination method available at present time. Our hypothesis is that a short DNA sequence (100-650bp long) can be used for species identification of medicinal plants. This kind of short DNA sequence is called a DNA barcode in the following text. Our long term goal is to (1) systematically determine DNA barcode(s) that can be used for the species identification of most, if not all, medicinal plants used in the TCMs, and compile them into a DNA barcode library; and (2) establish a standard procedure to amplify the barcode sequence(s) from a test sample and compare it to sequences from the DNA barcode library for species identification. The present study is a pilot study in an attempt to lay the ground for the future large scale DNA barcode identification project in all important medicinal plants used in TCM. This study intends to address the problem of misidentification of botanical raw materials that has been well-reported in the literature and media. For example, a “Siberian Ginseng” (Eleutherococcus Senticosus) product implicated in a case of neonatal androgenisation was found upon analysis to be an unrelated species, Chinese silk vine “Periploca Sepium” (1). In Hong Kong, encephalopathy and neuropathy associated with a Chinese herbal preparation purportedly made from the roots of Long-Dan-Cao (Gentiana Regescens) turned out to be due to another plant Podophyllum Emodi. In another example, more than 48 cases of renal poisoning attributed to fang-ji (Stephania Tetrandra) in weight-loss preparation were actually caused by Guang-Fang-Ji (Aristolochia Fangchi); aristolochic acid is a known nephrotoxin (2). The exactly extent of this problem can be much greater than what have been reported considering that only the cases having the most severe consequences would be reported. The result obtained from this study will lay the foundation for the development of a standard method that will eventually limit, if not able to eliminate the problems of misidentification, adulteration and contamination of botanical raw materials and botanical drug products. We plan to accomplish our goal through three specific aims: SPECIFIC AIM 1: To select the DNA sequence that can be used as DNA barcode for species determination of medicinal plants. Recent study has led to the concept of “DNA barcode”, which is a short to very short (100-650bp) sequence that server as a DNA marker or fingerprint and has the power to identify most, if not all organisms on Earth based on variability in the barcode sequences (3). An international consortium has been formed to systematically barcode life in different domains (http://barcoding.si.edu/index_detail.htm). A proof-of-concept study has showed that the cytochrome c oxidase I (COI) sequences can server as the core of a global bio-identification system for many animals. These studies suggest that using a single DNA barcode for species identification of medicinal plants is also possible. With very few sequence information available for most medicinal plants, we will depend on literature search to select the sequence most likely to represent the DNA barcode. SPECIFIC AIM 2: To establish a standard experimental procedure for species determination of medicinal plants under test. The procedure will mainly involve Polymerase Chain Reaction (PCR) following by automatic DNA sequencing. Although the standard procedure of PCR has been well established, we might still encounter several problems since we are trying to amplify DNA from samples containing botanical species belonging to a wide range of taxonomic groups. First, our PCR primers might not be universal enough to effectively and specifically amplify the intended DNA barcode from certain samples. Second, the DNA purification method might require substantial modification to extract DNA from certain botanical samples. Third, specific measures might have to be taken to remove potential DNA polymerase inhibitors in the botanical samples. Consequently, significant amount of efforts are expected to optimize the experimental conditions. The goal of this aim to establish a procedure that can be used in the future large scale project. SPECIFIC AIM 3: To build a pilot database of DNA barcodes from approximately two hundred medicinal plants. Using DNA fingerprinting for species identification in specific medicinal plants have been reported before. However, systematic efforts to identify universal DNA barcodes and to use these barcodes for species determination and identification have not been reported. After the successful completion of specific aim 1 and 2, we will extend the study to approximate 200 medicinal plants. This survey type of study will help us to evaluate the usefulness and robustness of the selected DNA barcode and the standard procedure developed above. This information will facilitate the design of the following large-scale DNA barcode determination project. In summary, this proposed study intends to carry out the pilot study that will eventually solve the practically critical problem of species identification of medicinal plants. The data generated from this study can have broad applications in a wide range of research areas. For example, it will generate important new insights into the diversification of life and the rules of molecular evolution. In addition, it will lay the ground work for the future development of a systematic, reliable, cost-effective and accessible solution to authenticate the botanical materials used for making TCMs.

List of Research Outputs

Liu C., Ghosh S., Searls D.B., Saunders A.M., Cossman J. and Roses A.D., Clusters of adjacent and similarly expressed genes across normal human tissues complicate comparative transcriptomic discovery, OMICS. USA, Mary Ann Liebert Inc, 2005, 9: 351-363.

Researcher : Wo SK

List of Research Outputs

Ng K.M., Che C.M., Wo S.K., Tam P.K.H. and Lau A.S.Y., Analytical Application of Acetate Anion in Negative Electrospray Ionization Mass Spectrometry for the Analysis of Triterpenoid Saponins - Ginsenosides , Rapid Communications in Mass Spectrometry. John Wiley and Sons, 2006, 20: 1545 - 1550.

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