DEPT OF BIOCHEMISTRY

Researcher : Cai K

List of Research Outputs

 

Cai K., Xu R. and Sham M.H., Adeno-associated virus vector-mediated angiogenic inhibitors suppress lung tumor growth in mice., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Researcher : Chan C

List of Research Outputs

 

Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Mechanistic insight into point mutations in sedlin that result in spondyloepiphyseal dysplasia tarda, FASEB Journal. 2006, 873.9.

 

Researcher : Chan CH

List of Research Outputs

 

Chan C.H., Ip M.S.M. and Shum D.K.Y., Heparan Sulfate/Syndecan-1 Modulates the Balance between Proteinase and Anti-Proteinase in Bronchiectasis, Proteoglycans in Signaling Stockholm (Runo), Sweden, September 7-11,2005.

 

Researcher : Chan CSL

List of Research Outputs

 

Chan C.S.L., Chan D., Cheah K.S.E. and Tanner J.A., Purification and targeting sclerostin: Steps towards, osteoporosis therapy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

 

Researcher : Chan D

Project Title:

A matrix metalloproteinase detector for in vitro monitoring of enzyme activity

Investigator(s):

Chan D, Lam E

Department:

Biochemistry

Source(s) of Funding:

Research Initiation Programme

Start Date:

06/2002

 

Abstract:

To establish efficient in vitro reporter assays for aggrecanase and other MMPs.

 

Project Title:

The role of matrix remodeling in endochondral bone formation

Investigator(s):

Chan D, Cheah KSE

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

10/2002

 

Abstract:

The project attempts to:- 1) create heterozygous and homzygous mouse mutants expressing MMP-resistant collagen X from the four embryonic stem (ES) cell clones; 2) perform detailed in virto and in vivo analysis to study the molecular and phenotypic consequences on endochondral bone formation.

 

Project Title:

Understanding the molecular basis of skeletal (digit) patterning defects in Brachydactylyl type A-1

Investigator(s):

Chan D, Cheah KSE, He L.

Department:

Biochemistry

Source(s) of Funding:

NSFC/RGC Joint Research Scheme

Start Date:

01/2003

Completion Date:

12/2005

 

Abstract:

To create a BDA-1 mouse model by gene targeting; to study the impact of the BDA-1 mutation on skeletal morphogenesis; to study the biochemical consequence of BDA-1 mutations using in vitro cell approaches.

 

Project Title:

The biology of digit formation and its pathology in brachydactyly

Investigator(s):

Chan D, Mundlos S.

Department:

Biochemistry

Source(s) of Funding:

Germany/Hong Kong Joint Research Scheme

Start Date:

01/2005

 

Abstract:

To characterize the Ihh-E95K mouse phenotype focusing on endochondral ossification and digit formation; to investigate interacting brachydactyly pathways using a genetic approach in mice; to create Hoxd13 targeting constructs with expanded poly-Als repeats and perform gene-targeting in ES cells.

 

Project Title:

Genomic analysis of the regulation of osteoblast activity in a mouse with generalized hyperostosis

Investigator(s):

Chan D

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2005

 

Abstract:

N/A

 

Project Title:

Genomic analysis of the regulation of osteoblast activity in a mouse with generalized hyperostosis

Investigator(s):

Chan D, Cheah KSE, Cheung KMC

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2005

 

Abstract:

To analyses of specific markers for known regulators of osteoblast differentiation, proliferation and biosynthetic activity; to use gene expression profiling using micro-arrays to gain insights into genes that are expressed in normal and 13del-tg osteoblasts to identify alterations in pathways as a consequence of expressing Col10-13del; to create a transgenic mouse expression of Col10-13del in osteoblasts to assess its expression and correlation to the hyperostosis phenotype.

 

List of Research Outputs

 

Abbah S.A., Lu W.W., Luk K.D.K., Cheung K.M.C., Liu W., Chan D., Li Z. and Leong J.C.Y., New Bone Formation by Injected With Osteogenic Cells Confined in Sodium Alginate Microcapsules, The XXIII SICOT/SIROT Triennial World Congress held in Istanbul, Turkey, September 2-9, 2005.

 

Abbah S.A., Lu W.W., Cheung K.M.C., Zhao F., Chan D., Liu W.G., Li Z., Leong J.C.Y. and Luk K.D.K., Polymer encapsulated human osteoblastic cells form ectopic bone in mice, 52nd Annual Meeting of Orthopaedic Research Society, Chicago, Illinois, March 19-22, 2006.

 

Aladin K.D.M., Lu W.W., Cheung K.M.C., Yeung K.W.K. and Chan D., Impact of Trp2 allele mutation of alpha-2 chain in collagen IX on the structural integrity of human annulus fibrosus, European Cells and Materials. 2005, 10(3): 53.

 

Aladin K.D.M., Lu W.W., Cheung K.M.C., Yeung K.W.K. and Chan D., Impact of Trp2 allele mutation of alpha-2 chain in collagen IX on the structural integrity of human annulus fibrosus, European Cells and Materials Symposium: Spinal Motion Segment: From Basic Science to Clinical Application, 4th to 7th July, 2005. Davos, Switzerland. 2005.

 

Aladin Kaderbatcha D.M., Lu W.W., Cheung K.M.C., Yeung K.W.K. and Chan D., Impact of the Trp2 allele mutation of the alpha-2 chain in collagen IX on the structural integrity of human annulus fibrosus., European Cells and Material: ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application. Davos, Switzerland, July 2005 . 2005.

 

Chan C.S.L., Chan D., Cheah K.S.E. and Tanner J.A., Purification and targeting sclerostin: Steps towards, osteoporosis therapy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

 

Chan D., Gao B., Hu J.X., Law K.F.S., He L. and Cheah K.S.E., Abnormal Indian Hedgehog Signaling affects Distal Digit Patterning in a Mouse Model with Brachydactyly Type A1, Frontiers in Biomedical Research, The Univeristy of Hong Kong, Hong Kong, Dec 2. 2005.

 

Chan D., ER stress alters the course of endochondral ossification, Max-Plank Institute for Molecular Genetics, Berlin, July 14. 2005.

 

Chan D., Tsang K.Y., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E. B., Yamada Y., Bateman J.F., Cheung K.M.C. and Cheah K.S.E., Endoplasmic reticulum stress and reprogramming of hypertrophic chondrocytes, Gordon Research Conference: Collagen. New London, New Hampshire USA, July. 2005.

 

Chan D., Chan W.Y., Murphy G. and Cheah K.S.E., Mouse model with impaired collagen X degradation at the chondr-osseous junction, International Workshop on the Skeletal Growth Plate, Portland, USA. June 11-15. 2006.

 

Chan D., Ho G. and Cheung K.M.C., Stem cell therapy for intervertebral disc degeneration, The Croucher Foundation Advanced Study Institute on Stem Cell Research, Nov 14-15. 2005.

 

Chan D. and Cheung K.M.C., The effect of severity of degeneration on mesenchymal stem cells' ability to regenerate the intervetebral disc: a rabbit model, Hansjoerg Wyss Foundation Oral Presentation Award European Cells and Materials VI / SRN I Spinal Motion Segment: From Basic Science to Clinical Application, July 4-7 2005. 2005.

 

Chan D., Ho G., Leong V.Y.L. and Cheung K.M.C., The effect of severity of disc degeration on mesenchymal stem cell's ability to regenerate the intervertebral disc., European Cells and Material: ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application. Davos, Switzerland, July 2005 . 2005.

 

Chan W.Y., Cheah K.S.E., Ng V.C.W., Murphy G. and Chan D., Mouse model with impaired collagen X degradation at the chondro-osseous junction, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006.

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25.

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September . 2005.

 

Cheung K.M.C., Chen Y., Karppinen J., Chan D., Jim J.J.T., Luk K.D.K., Ala-Kokko L., Leong J.C.Y., Ott J., Sham P.C., Cheah K.S.E. and Song Y., Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in Chinese, Spine. 2006, 31(10): 1143-8.

 

Cheung K.M.C., Jim J.J.T., Noponen-Hietala N., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The Genetics of intervertebral disc degenertation, European Cells and Material: ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application. Davos, Switzerland, July . 2005.

 

Cheung K.M.C., Lu W.W., Luk K.D.K., Wong C.T., Chan D., Shen J.X., Qiu G.X., Zheng Z.M., Li C.H., Liu S.L., Chan W.K. and Leong J.C.Y., Vertebroplasty by use of a strontium containing bioactive bone cement, Spine (Focus Issue). 2005, 30(17S): S84-S91.

 

Cheung K.M.C., Ho G., Chan D. and Leong V.Y.L., regeneration of nucleus pulposus after disectomy by autologous mesenchymal stem cells: a rabbit model, European Cells and Material: ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application. Davos, Switzerland, July 2005 . 2005.

 

Choi M.Y., Chan D., Cheah K.S.E. and Tanner J.A., Functional studies on sedlin, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, 3 Dec . 2005.

 

Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Mechanistic insight into point mutations in sedlin that result in spondyloepiphyseal dysplasia tarda, FASEB Journal. 2006, 873.9.

 

Guo X., Cheung K.M.C., Chan D. and Irwin M.G., Comparison of the effect of non-selective NSAID and Cycloosygenoase-2 (COX-2) selective NSAID on bone formation - implications for spinal fusion, 40th Annual Meeting of Scoliosis Research Society, Miami, Florida, USA, October 27-30, 2005.

 

Guo X., Irwin M.G., Chan D., Tipoe G.L. and Cheung K.M.C., Differential functions of cyclooxygenase 1 and 2 in bone repair, European Cells and Materials. 2005, 10(3): 56.

 

Guo X., Irwin M.G., Cheung K.M.C., Chan D. and Tipoe G.L., The Role of Cyclooxygenase 1 and 2 in Bone Repair, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S.P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on familial Early-onset Degenerative Disc Disease(DDD), Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland.. 2006.

 

Hui T.Y., Ho G., Cheung K.M.C., Chan D., Cheung W.L. and Chan B.P., Rabbit bone marrow derived mesenchymal stem cells induced collagen gel contraction-fabrication of tissue-like structures with different cell densities, Tissue Engineering. May Ann Liebut, Inc., 2005, 110.

 

Jim J.J.T., Noponen-Hietala N., Cheung K.M.C., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration, Spine. 2005, 30: 2735-2742.

 

Leung V.Y.L., Ho G., Chan D. and Cheung K.M.C., The effect of severity of degeneration on intervertebral disc regeneration by autologous mesenchymal stem cells, 25th Annual Congress of the Hong Kong Orthopaedic Association, Nov 19-20 2005, Hong Kong. 2005.

 

Leung Y.L., Chan D. and Cheung K.M.C., Regeneration of intervertebral disc by mesenchymal stem cells: Potentials, limitations, and future direction, Eur Spine J. 2006, 15 Suppl 15: 406-13.

 

Leung Y.L., Ho G., Chan D. and Cheung K.M.C., The effect of severity of degeneration on intervertebral disc regeneration by use of mesenchymal stem cells, 52nd Annual Meeting of Orthopaedic Research Society, Chicago, Illinois, March 19-22, 2006.

 

Leung Y.L., Ho G., Cheung K.M.C. and Chan D., The effect of severity of degeneration on intervertebral disc regeneration by use of mesenchymal stem cells, European Cells & Materials Conference, Davos, Switzerland. 2005.

 

Li Z., Lu W.W., Ni G., Lam W.M.R., Chan D., Abbah S.A., Yang F., Cheung K.M.C. and Luk K.D.K., Strontium combined with calcium increases vertebral bone mineral density and stiffness in goats, 25th Annual Congress of the Hong Kong Orthopaedic Association, Nov 19-20 2005, Hong Kong. 2005.

 

Lo R.L.K., Ng V.C.W., Cheah K.S.E. and Chan D., ER-stress signaling and chondrocyte differentiation in mice, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005.

 

Song Y., Ho D.W.H., Cheung K.M.C., Karppinen J., YIP S. P., Leong J.C.Y., Ott J., Luk K.D.K., Cheah K.S.E., Sham P.C. and Chan D., Genetic Linkage analysis of early onset degenerative disc disease in Southern Chinese., HUGO Pacific meeting & Asia-pacific Human Genetics Conference (HUGO-AP 2006), March 6-10, 2006 Academica Sinica, Taipei. 2006.

 

Tsang K.Y., Chan D., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B., Yamada Y., Bateman J.F., Cheung K.M.C. and Cheah K.S.E., Chondroctes Alleviate ER Stress Caused by Unfolded Proteins by Reprogramming, The British Society for Matrix Biology. 25th Anniversary Meeting Pathobiology of Bone and Cartilage. Manchester, UK, 12-13 September . 2005.

 

Yee A.F.Y., Cheung K.M.C. and Chan D., Gene and Protein Expression Profiles of the Intervertebral Disc: In Health and Disease - A General Overview, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Yeung K.W.K., Poon R.W., Liu X.Y., Ho J.P., Chung C.Y., Chu P.K., Lu W.W., Chan D. and Cheung K.M.C., Corrosion resistance, mechanical properties and cyto-compatibility of NiTi shape memory alloys using nitrogen, and oxygen plasma immersion ion implantation, Journal of Biomedical Materials Research: Part A. 2005, 75: 256-67.

 

Yeung K.W.K., Poon R.W.Y., Liu X.Y., Ho J.P.Y., Chung C.Y., Chu P.Y., Lu W.W., Chan D. and Cheung K.M.C., Enhanced corrosion resistance and biocompatibility by plasma implantation of nickel-titanium alloys: An in-vitro and surface chemical study, 51st Annual Meeting of Orthopaedic Research Society, Washington DC, U.S.A., 2005.

 

Yeung K.W.K., Poon R.W.Y., Liu X., Ho J.P.Y., Chung C.Y., Chu P.K., Lu W.W., Chan D. and Cheung K.M.C., Nickel suppression in Ni-Ti alloys by plasma immersion ion implantation surface treatment: new materials for orthopaedic implantation, European Cells and Materials. 2005, 10(3): 78.

 

Yeung K.W.K., Poon R.W.Y., Liu X., Ho J.P.Y., Chung C.Y., Chu P.K., Wu W.W., Chan D. and Cheung K.M.C., Nickle suppression in Nickle-titanium alloys by plasma immersion ion implanation surface treatmentL new material for orthopaedic implanation., European Cells and Material: ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application. Davos, Switzerland, July 2005 . 2005.

 

Yeung K.W.K., Poon R.W., Liu X.Y., Chung C.Y., Chu P.K., Lu W.W., Chan D. and Cheung K.M.C., Nitrogen Plasma Immersion Ion Implanted Nickel Titanium Alloys For Orthopedic Use, 5th Asian-European International Conference on Plasma Surface Engineering, Qingdao, China, Sept 12-16, 2005.. 2005.

 

Yeung K.W.K., Poon R.W.Y., Liu X.Y., Chung C.Y., Chu P.K., Lu W.W., Chan D. and Cheung K.M.C., Nitrogen plasma immersion ion implanted nickel titanium alloys for orthopedic use, 5th Asian-European International Conference on Plasma Surface Engineering, Qingdao, PR China, September 12-16. 2005.

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Expression of heparanase in newborn mouse growth plates, Glycoconjugate Journal, GlycoXVIII, XVIII International Symposium on Glycoconjugates, Firenze, Italy. 2005.

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan Sulfates and Heparanase in the Mineralizing Matrix of Developing Mouse Growth Plate., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan sulfates and heparanase at the mineralization front of the developing growth plate., Proteoglycans in Signaling, Stockholm (Runo), Sweden, September 7-11,2005.

 

Researcher : Chan KMJ

List of Research Outputs

 

Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785.

 

Researcher : Chan KT

Project Title:

Investigation of novel RNA-mediated regulation of Hoxb3 gene expression profiles

Investigator(s):

Chan KT, Sham MH

Department:

Biochemistry

Source(s) of Funding:

Small Project Funding

Start Date:

11/2005

Completion Date:

11/2006

 

Abstract:

Hox homeobox genes are transcription factor genes with a clustered genomic organization in both mouse and human. The temporal and spatial specific expressions of Hox genes are essential for their function in regulating a variety of embryonic developmental processes. Recent studies on micro RNA genes in mammalian genomes demonstrated that there are a number of micro RNA genes present within Hox gene clusters. These micro RNA products have specific functions in regulating the expressions of target Hox genes, suggesting that apart from known regulatory mechanisms, RNA-mediated gene expression regulation is important of normal Hox gene function. To investigate RNA mediated control of Hox gene expression, we have performed pilot experiments by both in-silico and experimental approaches. From available databases, we have identified wide-spread conserved anti-sense RNA transcripts in all four Hox gene clusters in the mouse and human genomes, suggesting that these anti-sense RNAs may have important functions in Hox gene regulation. Moreover, we have identified a novel Hoxb3 anti-sense RNA which is expressed in a tissue-specific manner during mouse neural development. Similar anti-sense RNA transcript expression has also been observed for the human HoxA3 gene. Based on these observations, we hypothesize that these anti-sense RNA transcripts may be important for regulating Hox gene expression; and that RNA sequence mediated gene regulation may be a common mechanism for Hox gene regulation. The specific objectives of this project are: (1) To build up a complete expression profile of the differential mRNA transcripts for Hox genes; (2) To characterize both the structure and the expression patterns of the Hoxb3 anti-sense RNA transcript at different stages of mouse embryogeneis; (3) To perform a cell based functional analysis to examine the effect of anti-sense RNA on the expression of the normal Hoxb3 sense mRNA transcript.

 

List of Research Outputs

 

Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Chan LC

List of Research Outputs

 

Ng M.H., Jin D. and Chan L.C., Ras Signalling in Mll-Mediated Leukaemia, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Chan SF

List of Research Outputs

 

Ching Y.P., Chan S.F. and Jin D., A centrosomal target of human T-cell leukemia virus type I oncoprotein Tax on the road to genome instability, The Croucher Advanced Study Institute “Signaling in Cell Growth abd Differentiation”. The Hong Kong University of Science and Technology, Hong Kong, January 16-20, 2006.

 

Ng D.C.H., Chan S.F., Kok K.H., Yam J.W.P., Ching Y.P., Ng I.O.L. and Jin D., Mitochondrial targeting of growth suppressor protein DLC2 through the START domain, FEBS Letters . 2006, 580(1): 191-8.

 

Researcher : Chan SY

List of Research Outputs

 

Tang L.F., Chan S.Y., Sham P.C. and Song Y., In silico mapping of quantitative trait loci affecting bone mineral density in mice., HUGO Pacific meeting & Asia-Pacific Human Genetics Conference (HUGO-AP 2006) March 6-10,2006 Academica Sinica, Taipei. 2006.

 

Researcher : Chan WCW

List of Research Outputs

 

Chan D., Tsang K.Y., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B., Yamada Y., Bateman J.F., Cheung K.M.C. and Cheah K.S.E., Endoplasmic reticulum stress and reprogramming of hypertrophic chondrocytes, Gordon Research Conference: Collagen. New London, New Hampshire USA, July. 2005.

 

Tsang K.Y., Chan D., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B., Yamada Y., Bateman J.F., Cheung K.M.C. and Cheah K.S.E., Chondroctes Alleviate ER Stress Caused by Unfolded Proteins by Reprogramming, The British Society for Matrix Biology. 25th Anniversary Meeting Pathobiology of Bone and Cartilage. Manchester, UK, 12-13 September . 2005.

 

Researcher : Chan WY

List of Research Outputs

 

Chan D., Chan W.Y., Murphy G. and Cheah K.S.E., Mouse model with impaired collagen X degradation at the chondr-osseous junction, International Workshop on the Skeletal Growth Plate, Portland, USA. June 11-15. 2006.

 

Chan W.Y., Cheah K.S.E., Ng V.C.W., Murphy G. and Chan D., Mouse model with impaired collagen X degradation at the chondro-osseous junction, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

 

Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia . 2005.

 

Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Hoxb3 is involved in the endothelin-1 signaling pathway in patterning the facial branchial arches, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005.

 

Researcher : Chau CH

List of Research Outputs

 

Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42.

 

Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57.

 

Researcher : Chau PYP

List of Research Outputs

 

Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785.

 

Researcher : Cheah KSE

Project Title:

The role of Type II procollagens encoded by alternatively spliced forms of aI(II) procollagen mRNA in cartilage differnetiation and growth

Investigator(s):

Cheah KSE

Department:

Biochemistry

Source(s) of Funding:

Arthritis and Rheumatism Council (ARC) - General Award

Start Date:

12/1993

 

Abstract:

To gain insight into the function of type IIA procollagen by: a) performing a loss-of function test by introducing into the mouse germ line, a mutation in the [alpha]1(II) collagen gene in which exon 2 is deleted, using gene targeting; determining the phenoypic consequence of reduced levels of expression or failure to express type IIA procollage; generating monoclonal antibodies to the cysteine-rich domain within the aminopropeptide of type IIA procollagen.

 

Project Title:

Defining the role of the transcription factor Sox9 in skeletal development by tissue-specific gene inactivation

Investigator(s):

Cheah KSE, Lovell-Badge R.H.

Department:

Biochemistry

Source(s) of Funding:

UK/Hong Kong Joint Research Scheme

Start Date:

02/1998

 

Abstract:

To inactivate the mouse Sox9 gene selectively and specifically in developing cartilage tissue in order to understand the role of Sox9 in skeletal formation and the relationship between loss of Sox9 gene function and skeletal malformation.

 

Project Title:

Molecular and transgenic approaches for the identification of genes regulated by SOX9 during mouse development

Investigator(s):

Cheah KSE

Department:

Biochemistry

Source(s) of Funding:

Outstanding RGC Projects

Start Date:

09/1998

 

Abstract:

To use a combination of molecular cloning, cell culture and transgenic/chimeric mouse approaches to: 1) identify other downstream targets of SOX9; 2) test the possibility that SOX9 may have a role as a negative regulator of transcription; 3) study SOX9 function by determining the developmental consequences of mis-expression of the gene in transgenic mice. These studies will provide fundatmental information on the mechanisms by which SOX9 regulates gene expression, with profound implications for understanding it's development role and the molecular basis of CD caused by loss of SOX9 function.

 

Project Title:

In vivo functional analysis of the SOX9 transcription factor in regulating developmental gene expression

Investigator(s):

Cheah KSE, Chan D, Tam P.P.L.

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2001

Completion Date:

08/2005

 

Abstract:

To use transactivation of the COL2A1 enhancer reporter upon ectopic expression of SOX in transgenic mice to assess: i) the functional requirement for SOX9 to activate its target genes by testing the competence of SOX2 and SOX8 to substitute for SOX9; ii) the requirements for the N-, HMG, C terminus regions of SOX9 in activating its target genes by testing the competence of SOX9-SOX2 and SOX9-SOX8 chimeric proteins to substitute for SOX9 by gene targeting into the Sox9 locus in mouse ES cells, to test further the competence of the alternative SOX gene and/or relevant chimeric SOX protein to mediate the differentiation and developmental roles of SOX9, with particular focus on chondrogenesis.

 

Project Title:

Genomic approaches to uncover functionally relevant signalling pathways in craniofacial development

Investigator(s):

Cheah KSE, Wong BCW, Sham MH, Chung SK, Huang J, Smith DK, Wicking C.A., Yang MMS, Chow KL, Tam P.P.L.

Department:

Biochemistry

Source(s) of Funding:

Central Allocation Vote - Group Research Project

Start Date:

06/2002

 

Abstract:

To build a multidisciplinary, competitive and productive research team of a critical size with the central theme of uncovering genetic relationships and functionally relevant signalling pathways in craniofacial development in order to make an impact in this important research area, currently at the fore-front of genomic biology; to pool expertise and resources, employing complementary genetic approaches in mice, coupled with advanced technology to reveal networks of genes and the complex interactions that specify morphology of the head skeleton and facial structures; to use and develop bioinformatics tools to analyse the expression data and formulate hypotheses on genetic relationships and the pathways regulating patterning, formation and growth of the craniofacial primordia; to test the hypotheses on potential functional relationships and molecular interactions revealed by the bioinformatic analyses, in the worm model and in the yeast two hybrid system.

 

Project Title:

The regulation and role of Sox2 in the circling, deaf and yellow mouse mutants Yellow submarine (Ysb) and Light coat and circling (Lcc)

Investigator(s):

Cheah KSE

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

10/2002

Completion Date:

09/2006

 

Abstract:

The current project will test some hypotheses of Sox2 function using gene mapping, comparative genomics, genetics and transgenesis to: - i) identify the chromosomal breakpoints in Lcc; ii) identify the mutations in Ysb and Lcc and determine whether these have disrupted cis-elements which regulate Sox2 expression in the inner ear and hair follicle; iii) validate these findings by functional rescue/mutagenesis/genetic experiments in transgenic mice; iv) identify the molecular developmental changes in inner ear hair cell and hair follicle morphogenesis.

 

Project Title:

Understanding gene function and molecular bases of disease using transgenic and gene targeting technology

Investigator(s):

Cheah KSE, Chan SY, Chan LC, Sham MH, Chung SK, Chow BKC, Kung H, Chan D, Huang J, Lin MC, Zhang JCL, Waye MMY, Lung M.L., Chow KL, Tam P.P.L., Chan W.Y., Lui VCH, Yao KM

Department:

Biochemistry

Source(s) of Funding:

Central Allocation Vote - Group Research Project

Start Date:

06/2003

Completion Date:

05/2006

 

Abstract:

To continue to build up a multidisciplinary, competitive and productive research team of a critical size pooling expertise and resources to tackle several fore-front issues of human diseases using animal models; to maintain a highly productive Transgenic Core Facility (TCF) with extended "clientele", facilitating the timely generation of genetically modified mice for more projects which will serve to provide new knowledge in understanding gene function and as models of human disease, provide insight into the molecular pathogenesis of disease.

 

Project Title:

Genetic manipulation and analyses of the regulation of chondrocyte hypertrophy

Investigator(s):

Cheah KSE, Chan D

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2003

 

Abstract:

To understand the roles of Ihh and Ppr specifically in hypertrophic chondrocytes (HCs) and will dissect the mode of action of the Ihh and PPR pathways in HCs, in vivo, in transgenic and conditional knockout mice, Specially we will: 1) Investigate whether abnormal Ihh signaling and /or processing in 13del HCs is a primary cause of the differentiation abnormality by a) ablating Smoothened (Smo), the transducer of Ihh signaling in 13 del and wild-type HCs and b) over-expressing either Ihh or a non-secreted and unprocessed form of Ihh in normal HCs. 2) By the same rationale, study the role of the PTHrP/PPR pathway by ablating PPR in 13 del and wild-type HCs.

 

Project Title:

Functional analysis of SM22[beta] by tissue-specific targeted deletion in mice

Investigator(s):

Cheah KSE, Lau CP, Feil R., Parmacek M.S., Zhang JCL

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2003

 

Abstract:

To determine the general role of SM22[beta] in a cell; to understand the specific role of SM22[beta] in cardiovascular development.

 

Project Title:

Genetic manipulation and analyses of the regulation of chondrocyte hypertrophy

Investigator(s):

Cheah KSE, Chan D

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

09/2003

 

Abstract:

N/A

 

Project Title:

Strategic research theme of development and reproduction under the strategic research area of health development framework and seed funding proposal

Investigator(s):

Cheah KSE, Ho PC, Wong WT, Sham PC, Chin FYL, Chan BP

Department:

Biochemistry

Source(s) of Funding:

Seed Funding for Strategic Research Theme

Start Date:

05/2005

 

Abstract:

To promote and facilitate partnership that are highly interactive, collaborative and multidisciplinary; to achieve research excellence in the fields of development and reproduction and, through their translation, better treatment and prevention of diseases; to raise community awares and understanding of important issues and advances concerning healthy development and reproduction and treatment of diseases.

 

Project Title:

Functional and genetic analyses of the role of type IIA procollagen in morphogenesis and as a regulator of BMP and TGFβ signaling

Investigator(s):

Cheah KSE

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

08/2005

 

Abstract:

N/A

 

Project Title:

Functional and genetic analyses of the role of type IIA procollagen in morphogenesis and as a regulator of BMP and TGFβ signaling

Investigator(s):

Cheah KSE, Chan D

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

08/2005

 

Abstract:

To address the hypothess that IIA regulates nodal signaling by a) maintaining the midline barrier or b) by interacting with Nodal protein.

 

Project Title:

Genomic approaches to uncover functionally relevant signalling pathways in craniofacial development

Investigator(s):

Cheah KSE, Chan WY, Chow KL, Huang J, Sham MH, Smith DK, Bronner-Fraser M, Fraser SE, Tam PPL, Wu DKW, Chung SK, Zhou Z

Department:

Biochemistry

Source(s) of Funding:

Central Allocation Vote - Group Research Project

Start Date:

03/2006

 

Abstract:

To uncover and understand the roles of two sets of transcription factor genes: Hos genes in establishing the complex pattern and structures of the inner ear and middle ear; and Sox9 and Sox10 in the early induction of the inner ear and the later specification of cell fate or type; to generate hypotheses on genetic relationships, molecular interactions and pathways involving Hoxa/b, Six1, Sox9 and Sox10 using simpler model systems such as the worm; to validate the hypotheses on molecular interactions by molecular, biochemical and cellular approaches.

 

List of Research Outputs

 

Au T.Y.K., Wynn S.L., Cheah K.S.E. and Cheung K.M.C., The use of a mouse model to understand the role of SOX9 in campomelic dysplasia and the notochord, 25th Annual Congress of the Hong Kong Orthopaedic Association, Nov 19-20 2005, Hong Kong. 2005.

 

Au Y.K., Wynn S.L., Cheung K.M.C. and Cheah K.S.E., Foxa2 minimal notochord enhancer element mediates Cre expression in the node and notochord, Mechanisms of Development. 2005, 122 (Supp 1): S88.

 

Au Y.K., Wynn S.L., Cheung K.M.C. and Cheah K.S.E., Foxa2 minimal notochord enhancer element mediates Cre expression in the node and notochord, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia. 2005.

 

Au Y.K., Cheung K.M.C. and Cheah K.S.E., In vivo functional analysis of SOX9 by conditional expression of a mutant SOX9, SOx9Y440X, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec. 2005.

 

Chan C.C.Y., Luk K.D.K. and Cheah K.S.E., Understanding the function of the SEDL gene and the molecular pathogenesis of spondyloepiphyseal dysplasia tarda, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

 

Chan C.S.L., Chan D., Cheah K.S.E. and Tanner J.A., Purification and targeting sclerostin: Steps towards, osteoporosis therapy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

 

Chan D., Gao B., Hu J.X., Law K.F.S., He L. and Cheah K.S.E., Abnormal Indian Hedgehog Signaling affects Distal Digit Patterning in a Mouse Model with Brachydactyly Type A1, Frontiers in Biomedical Research, The Univeristy of Hong Kong, Hong Kong, Dec 2. 2005.

 

Chan D., Tsang K.Y., Cheslett D., Chan W.C.W., So C.L., Kwan K. M., Hunziker E.B., Yamada Y., Bateman J.F., Cheung K.M.C. and Cheah K.S.E., Endoplasmic reticulum stress and reprogramming of hypertrophic chondrocytes, Gordon Research Conference: Collagen. New London, New Hampshire USA, July. 2005.

 

Chan D., Chan W.Y., Murphy G. and Cheah K.S.E., Mouse model with impaired collagen X degradation at the chondr-osseous junction, International Workshop on the Skeletal Growth Plate, Portland, USA. June 11-15. 2006.

 

Chan W.Y., Cheah K.S.E., Ng V.C.W., Murphy G. and Chan D., Mouse model with impaired collagen X degradation at the chondro-osseous junction, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

 

Cheah K.S.E., ER stress in the hypertrophic chondrocyte. , Workshop on the Skeletal Growth Plate, 11-15 June 2006, Portland, USA. . 2006.

 

Cheah K.S.E. and Zhang J.C.L., Procollagen IIA deficient mice. , US Patent application no. PTC/CN2005/001114. pending . 2005.

 

Cheah K.S.E., Chair a session and invited speaker, in Gordon Research Conference on Collagen, 24-29 July, 2005 in Boston, USA. 2005.

 

Cheah K.S.E., Chair a session and invited sympoisum speaker in 6th Pan Pacific Connective Tissue Societies Symposium, 30 November - 5 December 2005, Kohala Cost, Hawaii. 2005.

 

Cheah K.S.E., Discovering the crucial link for sensory development in the inner ear, Invited scientific talk at Institute of Biomedical Science, Hong Kong Branch, 19 May 2006 Hong Kong . 2006.

 

Cheah K.S.E., Discussion leader and speaker in Gordon Research Conference on Collagen, 24-29 July 2005, Boston, USA . 2005.

 

Cheah K.S.E., Genetic basis of skeletal dysplasia, ear development & congenital deafness – lessons from mose models of human malformations, Invited seminar at Hong Kong College of Paediatricians, 27 November 2005 Hong Kong. 2005.

 

Cheah K.S.E., Member, Scientific Programme Committee , HGM2006 (Human Genome meeting) , Helsinki, Finland. 2006.

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006.

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25.

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September . 2005.

 

Cheah K.S.E., Sox2 as a master regulator of prosensory development in the mouse inner ear, Invited seminar at Department of Biochemistry, the Chinese University of Hong Kong, 24 June 2006 Hong Kong. 2006.

 

Cheah K.S.E., Sox2, Sox18 and hair follicle development. , Sox Meeting, 30 August – 2 September 2005, Palm Cove, Australia.. 2005.

 

Cheah K.S.E., The role of Sox genes in inner ear development, Invited seminar at the Institute of Molecular and Cell Biology, National University of Singapore, 8 March 2006 Singapore. 2006.

 

Cheah K.S.E., The role of procollagen IIA as a facilitator of BMP signaling in Heart development, Croucher Advanced Study Institute [ASI] on Signaling in Cell Growth and Differentiation, HKUST 16-20 January 2006 Hong Kong. 2006.

 

Cheah K.S.E., The role of procollagen IIA as a facilitator of BMP signaling, 6th Pan Pacific Connective Tissue Societies symposium 30 November - 3 December, Kohala Cost, Hawaii, USA. . 2005.

 

Cheah K.S.E., Unraveling pathways and disease mechanisms using mouse models, Transcriptome 2005 International Conferences, Shanghai, China 5-9 November 2005. 2005.

 

Cheung K.M.C., Chen Y., Karppinen J., Chan D., Jim J.J.T., Luk K.D.K., Ala-Kokko L., Leong J.C.Y., Ott J., Sham P.C., Cheah K.S.E. and Song Y., Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in Chinese, Spine. 2006, 31(10): 1143-8.

 

Cheung K.M.C., Jim J.J.T., Noponen-Hietala N., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The Genetics of intervertebral disc degenertation, European Cells and Material: ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application. Davos, Switzerland, July . 2005.

 

Choi M.Y., Chan D., Cheah K.S.E. and Tanner J.A., Functional studies on sedlin, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, 3 Dec . 2005.

 

Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Mechanistic insight into point mutations in sedlin that result in spondyloepiphyseal dysplasia tarda, FASEB Journal. 2006, 873.9.

 

Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S.P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on familial Early-onset Degenerative Disc Disease(DDD), Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland.. 2006.

 

Jim J.J.T., Noponen-Hietala N., Cheung K.M.C., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration, Spine. 2005, 30: 2735-2742.

 

Kong C.T., Sham M.H., So C.W.E., Cheah K.S.E., Chen S.J. and Chan L.C., The Mll-Een knockin fusion gene enhances proliferation of myeloid progenitors derived from mouse embryonic stem cells and causes myeloid leukaemia in chimeric mice, Leukemia. 2006, 20: 1829–1839.

 

Li J. and Cheah K.S.E., The role of Indian Hedgehog in chondrocyte hypertrophy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005.

 

Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785.

 

Lo R.L.K., Ng V.C.W., Cheah K.S.E. and Chan D., ER-stress signaling and chondrocyte differentiation in mice, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005.

 

Song Y., Ho D.W.H., Cheung K.M.C., Karppinen J., YIP S.P., Leong J.C.Y., Ott J., Luk K.D.K., Cheah K.S.E., Sham P.C. and Chan D., Genetic Linkage analysis of early onset degenerative disc disease in Southern Chinese., HUGO Pacific meeting & Asia-pacific Human Genetics Conference (HUGO-AP 2006), March 6-10, 2006 Academica Sinica, Taipei. 2006.

 

Tsang K.Y., Chan D., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B., Yamada Y., Bateman J.F., Cheung K.M.C. and Cheah K.S.E., Chondroctes Alleviate ER Stress Caused by Unfolded Proteins by Reprogramming, The British Society for Matrix Biology. 25th Anniversary Meeting Pathobiology of Bone and Cartilage. Manchester, UK, 12-13 September . 2005.

 

Wong E.Y.M., Chan Y.S., Wu D.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in mouse hindbrain causes abnormal ear development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September . 2005.

 

Wong E.Y.M., Chan Y.S., Wu D.K. and Cheah K.S.E., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development., Mechanisms of Development . 2005, 122 (Supp 1): S88.

 

Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia . 2005.

 

Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Hoxb3 is involved in the endothelin-1 signaling pathway in patterning the facial branchial arches, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005.

 

Researcher : Chen Y

List of Research Outputs

 

Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Hui K.C., Ng P.K.M., Mak W.W., Jin D. and Song Y., Association of the cholesterol 24S-hydroxylase polymorphism with Alzheimer's disease in Chinese, HUGO 2006 Helsinki, Finland, 31 May-03 June 2006 . 2006.

 

Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Ng K.M., Mak W., Jin D., st. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese. , Dement Geriatr Cogn Disord. 2006, 22: 399-404.

 

Researcher : Cheng LYL

Project Title:

A concordance study of the importance of autosomal short tandem repeat (STR) and Y-chromosome STR in the Chinese community

Investigator(s):

Cheng LYL, Tan-Un KC

Department:

Biochemistry

Source(s) of Funding:

Small Project Funding

Start Date:

11/2002

 

Abstract:

In recent years, Short Tandem repeat (STR) and microsatellite analyses offer invaluable evidences in forensic science casework in court. Despite the well established database in the US forensic system, an Asian population database urgently needed to be established. In this research study, we use the STR markers that suit the American Combined DNA index system (CODIS) required by FBI to analyse Asian Chinese samples. Hence, the frequency of the allele for each locus can be calculated statistically, and stored for the use of the Chinese community.

 

List of Research Outputs

 

Lai K.K.S., Lo I.F.M., Tong T.M.F., Cheng L.Y.L. and Lam S.T.S., Detecting exon deletions and duplications of the DMD gene using Multiplex Ligation-dependent Probe Amplification (MLPA)., Clinical Biochemistry. 2005.

 

Researcher : Cheung MS

List of Research Outputs

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific Community - Stem Cells, Senescence and Cancer. Singapore, Oct 25 - Oct 30, 2005.

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Researcher : Chin KT

List of Research Outputs

 

Chin K.T., Wong C.M., Ng I.O.L. and Jin D., Functional characterization of liver-enriched transcription factor CREB-H (poster 1989). , The American Society for Cell Biology 45th Annual Meeting, San Francisco, California, USA, December 10-14, 2005.. 2005.

 

Chin K.T., Siu Y.T., Siu K.L. and Jin D., Tax-induced recruitment of TORC family coactivators is required for transcriptional activation of the human T-cell leukemia virus type 1 long terminal repeats (invited discussant). , The Leukemia and Lymphoma Society's 2005 Stohlman Scholars Symposium, Renaissance Scottsdale Resort, Arizona, USA, September 23-24, 2005. . 2005.

 

Researcher : Ching YP

Project Title:

The functional characterisation of Pak5 and caspase 4 interaction- a role in apoptosis

Investigator(s):

Ching YP

Department:

Pathology

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

02/2004

Completion Date:

01/2006

 

Abstract:

To confirm the interaction of Pak5 and caspase 4 using three independent assays, including co-immunoprecipitation, co-immunostaining and GST affinity pull down assays; to map the minimal binding region of these two proteins and develop functional assays to assess the functional outcome of this interaction; to determine if Pak5 plays a role in apoptosis by regulating the caspase 4.

 

Project Title:

Roles and regulation of group II p21-activated protein kinases:-implications in cancer metastasis

Investigator(s):

Ching YP

Department:

Pathology

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2005

 

Abstract:

N/A

 

Project Title:

Roles and regulation of group II p21-activated protein kinases:-implications in cancer metastasis

Investigator(s):

Ching YP, Jin D, Ng IOL

Department:

Pathology

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2005

 

Abstract:

To study: (1) Characterisation of the interaction between Pak5 and NM23 i) co-immunoprecipitation of Pak5 adn NM23 ii) defining the binding domain between Pak 5 and NM23 iii) xploring the interaction between Pak4 adn NM23. (2) Impact of Pak5-NM23 interaction in the biochemical properties of Pak5 and NM23 i) nucleotide diphosphate kinase activity ii) GTPase activating activity iii) in vitro kinase activity iv) subcellular localisation. 3) Roles of PakII in cancer metastasis using HCC as a model i) expression profile of Pak4 in HCC ii) clinicopathological analysis iii) cell invasion assay.

 

Project Title:

Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer

Investigator(s):

Ching YP

Department:

Pathology

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

07/2005

 

Abstract:

To characterize the overexpression of Pak1 protein and its activities in human HCC; to delineate the signaling pathways mediated by Pak1 in HCC; to investigate the roles of Pak1 in the metastasis of HCC.

 

Project Title:

Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer

Investigator(s):

Ching YP

Department:

Pathology

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2006

 

Abstract:

N/A

 

Project Title:

Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer

Investigator(s):

Ching YP, Ng IOL, Jin D, Yau TO

Department:

Pathology

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2006

 

Abstract:

(1) To characterize the mechanisms leading to Pak1 overexpression in human HCC; (2) to delineate the roles of Pak1 in hepatocarcinogenesis: (i) Phosphorylation of possible downstream targets of Pak1 in human HCCs. (ii) characterization of the tumorigenic activity of Pak1 in HCC cells. (iii) characterization of the anti-apoptotic activity of Pak1 in HCC cells. (3) to investigate the role of Pak1 in cancer metastasis: >(i) regulation of cell motility and cell adhesion by Pak1 in HCC cells. (ii) HGF/Rac1/Cdc42/Pak1 signaling in HCC metastasis. (iii) HGF/Pak1 mediated angiogenic activity. (iii) HGF/Pak1 mediated angiogenic activity.</I

 

Project Title:

Functional characterization of a putative tumour suppressor, AMP-activated protein kinase, in liver cancer

Investigator(s):

Ching YP

Department:

Pathology

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

02/2006

 

Abstract:

Purpose of study Liver cancer (hepatocellular carcinoma, HCC) is one of the most common cancers in the world, especially in Asia and Africa, and is the third most common fatal cancer in Hong Kong. While the risk factors are well defined, the underlying molecular mechanisms of HCC are still far from clear. Since the development of HCC is a multistep process, our long-standing interest is to identify tumour suppressor genes that play important roles in hepatocarcinogenesis. In our search, we have found that a hepatic kinase called AMP-activated protein kinase (AMPK), a key regulator for lipid and glucose metabolism in response to energy stress, is frequently downregulated in HCC cell lines and clinical samples (42%). Interestingly, recent discoveries have shown that tumour suppressors LKB1 and TSC2 lie upstream and downstream of AMPK, respectively, indicating that AMPK may be important in the regulation of cell growth, proliferation and apoptosis. Our pilot studies have also demonstrated that ectopic expression of the AMPK catalytic subunit in HepG2 cells significantly suppresses cell growth in colony formation assay. Conversely, HCC cell line with stable knockdown of AMPK catalystic subunit expression displays a much higher proliferation rate than that of the parental cell line (see research plan). These results suggest that AMPK possesses an activity to inhibit HCC cell growth. Here we propose to fully document the expression of AMPK and its effectors in HCC. We will explore the molecular basis of the underexpression of AMPK catalytic subunit in human HCC. We will also confirm the tumour suppressor activity of AMPK and delineate the molecular mechanisms by which loss of AMPK contributes to the formation of HCC. Findings derived from our work should shed important light on the pathogenesis of HCC and may provide novel targets for therapeutic intervention. Key issue and problem being address So far, the overall prognosis of HCC is unsatisfactory due to high incidence of recurrence and metastasis. It is therefore a high priority to unravel the molecular mechanisms underlying the pathogenesis of HCC so that better treatment modalities can be designed. In previous reports and our preliminary study, activation of AMPK has been demonstrated to play a role in suppressing the growth of cancer cells. These results prompt us to further address the pathogenic role of AMPK in HCC and to determine how dysregulation of AMPK leads to hepatocarcinogenesis. In this study, we will define the tumour suppressive function of AMPK in HCC and the regulatory roles of AMPK in cell signalling. Since AMPK is an important physiological regulator of cellular metabolism in response to nutrient stress and energy supply, our proposed study should advance our understanding on whether perturbation of energy metabolism can possibly linked to carcinogenesis. Results obtained in this study will derive novel insight on how the loss of AMPK function leads to the formation of cancer, aiming to provide opportunity for new molecular drug targets.

 

List of Research Outputs

 

Researcher : Choi MY

List of Research Outputs

 

Choi M.Y., Chan D., Cheah K.S.E. and Tanner J.A., Functional studies on sedlin, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, 3 Dec . 2005.

 

Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Mechanistic insight into point mutations in sedlin that result in spondyloepiphyseal dysplasia tarda, FASEB Journal. 2006, 873.9.

 

Researcher : Choy EYW

List of Research Outputs

 

Choy E.Y.W., Kok K.H. and Jin D., Construction of New DNA Vectors Based on Promoters of Epstein-Barr Virus-Encoded Small RNAS For Expression of Small Hairpin RNAS in Mammalian Cells., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Choy E.Y.W., Kok K.H. and Jin D., Construction of new DNA vectors based on promoters of Epstein-Barr virus-encoded small RNAs for expression of small hairpin RNAs in mammalian cells., Cold Spring Harbor Laboratory 2005 Meeting on RNAi, Cold Spring Harbor, New York, USA, September 28 to October 2, 2005. . 2005.

 

Researcher : Chun CS

List of Research Outputs

 

Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367.

 

Researcher : Dung WF

List of Research Outputs

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006.

 

Researcher : Garcia-Barcelo MM

Project Title:

Role of RET regulatory polymorphisms in Hirschsprung's disease

Investigator(s):

Garcia-Barcelo MM, Tam PKH, Ganster RW

Department:

Surgery

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

02/2004

Completion Date:

01/2006

 

Abstract:

To identify and functionally test a RET susceptibility locus which may predispose to disease more than 60% of the Chinese HSCR patients and to replicate our findings in an extended sample.

 

Project Title:

RET regulatory polymorphisms and susceptibility to Hirschsprung's disease

Investigator(s):

Garcia-Barcelo MM, Tam PKH, Ganster RW, Sham P.C.

Department:

Surgery

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2004

 

Abstract:

To study the effect of the RET promoter SNPs on transcription, independently and in conjection with other 5' cis-regulatory elements; to identify the transcription factor functioning at the SNPs site; to investigate whether there is functional and/or physical interactions between PHOX2B and the RET promoter; to test our genetic observations on a larger sample of Chinese HSCR patients; to investigate whether there is association between the transmission of HSCR-susceptibility RET haplotypes and PHOX2B-associated polymorphisms in affected individuals.

 

Project Title:

Study of the molecular basis of anorectal malformations

Investigator(s):

Garcia-Barcelo MM, Tam PKH, Lui VCH

Department:

Surgery

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

01/2005

Completion Date:

12/2005

 

Abstract:

The main objective of this project is: To evaluate the human SHH, GLI3, HOXD12, HOXD13, SALL1, HLXB9, EPHB2 genes as disease susceptibility loci for anorectal malformations. Data provided by mutant mice studies (mutant mice for these genes present with a phenotype resembling ARM) suggest that these genes are likely to be implicated in the pathology of ARM.

 

Project Title:

RET regulatory polymorphisms and susceptibility to Hirschsprung's disease

Investigator(s):

Garcia-Barcelo MM

Department:

Surgery

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2005

 

Abstract:

N/A

 

Project Title:

Study of the molecular basis of anorectal malformations

Investigator(s):

Garcia-Barcelo MM

Department:

Surgery

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2006

 

Abstract:

N/A

 

Project Title:

Study of the molecular basis of anorectal malformations

Investigator(s):

Garcia-Barcelo MM, Lui VCH, Yuan Z.W., Tam PKH

Department:

Surgery

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2006

 

Abstract:

To evaluate in patients with isolated ARM and/or VACTERL those genes known to be implicated in ARM according to data provided by i)mutant mice studies and, ii) their role in syndromes that include ARM as part of their spectrum (SHH, GLI3, HOXD12, HOXD13, SALL1, HLXB9, EPHB2); to investigate the gene expression profile during the development of the anorectal region in both, normal and teratogen (ethylenethiourea, ETU)-induced ARMs rat fetuses; to evaluate the genes differentially expressed in the control and in the teratogen ARM-induced embryos as candidates for ARM in humans.

 

List of Research Outputs

 

Researcher : Ho DWH

List of Research Outputs

 

Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S.P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on familial Early-onset Degenerative Disc Disease(DDD), Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland.. 2006.

 

Ho D.W.H., Polymorphism of Asporin Increases Susceptibility and Severity to Degenerative Disc Disease., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Song Y., Ho D.W.H., Cheung K.M.C., Karppinen J., YIP S.P., Leong J.C.Y., Ott J., Luk K.D.K., Cheah K.S.E., Sham P.C. and Chan D., Genetic Linkage analysis of early onset degenerative disc disease in Southern Chinese., HUGO Pacific meeting & Asia-pacific Human Genetics Conference (HUGO-AP 2006), March 6-10, 2006 Academica Sinica, Taipei. 2006.

 

Researcher : Huang J

Project Title:

Identification of myosin VA interacting proteins

Investigator(s):

Huang J, Wong NS, Pearlman R.E., Siu M.K.W.

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2001

Completion Date:

08/2005

 

Abstract:

To use biochemical, molecular biology and cell biology techniques to evaluate the candidates that are likely to be the proteins mediating MyoVA binding to the cargoes; to identify more MCP candidates as well as other proteins that are important for MyoVA function.

 

Project Title:

RNA-DNA hybrid oligonucleotide mediated site-specific repair and gene therapy

Investigator(s):

Huang J, Liu DP

Department:

Biochemistry

Source(s) of Funding:

Matching Fund for Hi-Tech Research and Development Program of China (863 Projects)

Start Date:

01/2003

 

Abstract:

To establish the reporter system for RDO and SSO mediated mutagenesis in mouse ES cells; to investigate the methods to improve the mutagenesis efficiency of RDO- and SSO-mediated mutagenesis; to study the mechanisms underlying SSO-mediated mutagenesis.

 

Project Title:

DNA recombineering mediated by single stranded oligonucleotides

Investigator(s):

Huang J, Cheah KSE, Watt RM, Liu DP

Department:

Biochemistry

Source(s) of Funding:

NSFC/RGC Joint Research Scheme

Start Date:

03/2003

Completion Date:

02/2006

 

Abstract:

To understand detailed biophysical characterization o the [beta] protein; to identify endogenous proteins essential for Red-mediated recombination in E. coli; to introduce [beta] into mammalian cell lines; to study the mechanism of SSO-mediated mutagenesis in mammalian cells.

 

Project Title:

Helicases as antiviral drug targets

Investigator(s):

Huang J, Zheng B, Sun H

Department:

Biochemistry

Source(s) of Funding:

Research Fund for the Control of Infectious Diseases - Full Grants

Start Date:

06/2004

Completion Date:

05/2006

 

Abstract:

To provide a foundation for antiviral drug development, we will expand our screen to identify more helicase inhibitors against SCV. We will also validate SCV helicase as drug target.

 

Project Title:

Development of a novel system for recombinant protein production

Investigator(s):

Huang J, Danchin A.L.M.

Department:

Biochemistry

Source(s) of Funding:

Seed Funding Programme for Applied Research

Start Date:

10/2004

Completion Date:

10/2005

 

Abstract:

To study in silicon identification of genetic elements necessary for high level protein production; to develop an efficient and versatile recombinant expression system for the expression of recombinant proteins; to carry out genetic modification of P. haloplanktis TAC125 for the improvement of protein production.

 

Project Title:

Development of an Efficient Recombinant Protein Expression System in Pseudoalteromonas haloplanktis TAC125

Investigator(s):

Huang J, Danchin A.L.M.

Department:

Biochemistry

Source(s) of Funding:

France/Hong Kong Joint Research Scheme - Travel Grants

Start Date:

01/2005

 

Abstract:

In silico identification of cold-adapted promoters, strongly and tightly regulated by simple environmental changes, genetic modifications necessary to improve protein production; development of an efficient and versatile recombinant expression system for the expression of recombinant proteins; genetic modification of Pesudoalteromonas haloplanktis TAC125 for the improvement of protein production.

 

Project Title:

Functions of the ubiquitously expressed kinesin in Purkinje neurons

Investigator(s):

Huang J, Yip HKF, Wu W, Mugnaini E., Copeland N.G., Jenkins NA

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2005

 

Abstract:

To determine the KhcU mutation effect on overall cerebellum development; to determine whether PC can project their processes to the target area; determine the localization of ER, Golgi complex, mitochondria, synaptic vesicles and lysosomes; to determine whether KhcU-mediated transport is required for normal MyoVA distribution and neurite out growth; to determine the ultrastructures of KhcU-deficiency PC.

 

Project Title:

Functions of the ubiquitously expressed kinesin in Purkinje neurons

Investigator(s):

Huang J

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2005

 

Abstract:

N/A

 

Project Title:

Determine the functions of the putative metal-binding domain of SARS-CoV helicase

Investigator(s):

Huang J, Sun H, Tanner JA, Watt RM

Department:

Biochemistry

Source(s) of Funding:

Research Fund for the Control of Infectious Diseases - Full Grants

Start Date:

02/2005

 

Abstract:

We aim to fully dissect the mechanism of bismuth-mediated SCV helicase inhibition on the molecular level, focussing on the manner in which zinc, bismuth and RNA interact with the MBD. Through this work, we will garner a detailed understanding of the role played by the MbD and the way in which it modulates helicase activity, aiding our development of more effective bismuth drugs.

 

Project Title:

Biochemical characterization of a putative helicase from a novel coronavirus that causes pneumonia

Investigator(s):

Huang J, Yuen KY

Department:

Biochemistry

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

02/2005

Completion Date:

01/2006

 

Abstract:

This study will provide the foundation for drug discovery to prevent a SARS-like outbreak by the novel CoV-HKU1. Our special aims are: (1) Clone, express and purify the putative helicase from CoV-HKU1; (2) Determine whether this protein exhibits an NTPase activity, and whether the NTPase activity is stimulated by the presence of single stranded DNA or RNA oligomers; (3) Investigate the RNA and DNA-duplex unwinding activities of the purified protein to establish beyond doubt that it is the functional viral helicase of the CoV-HKU1.

 

Project Title:

Role of kinesin-mediated intracellular transportation in Alzheimer's Disease

Investigator(s):

Huang J

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2006

 

Abstract:

N/A

 

Project Title:

Role of kinesin-mediated intracellular transportation in Alzheimer's Disease

Investigator(s):

Huang J, Song Y, Copeland NG, Jenkins NA, St George-Hyslop P, Westaway D, Wu W

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2006

 

Abstract:

(1) generation of mouse models with intracellular transport deficiency; (2) neuropathological analysis of the AD mouse models; (3) characterization of intracellular transportation in the mutant mice and primary cell cultures

 

List of Research Outputs

 

Bernini A., Spiga O., Venditti V., Prischi F., Bracci L., Huang J., Tanner J.A. and Niccolai N., Tertiary structure prediction of SARS coronavirus helicase, Biochem Biophys Res Commun. 2006, 343: 1101-1104.

 

Ge R., Watt R.M., Sun X., Tanner J.A., He Q., Huang J. and Sun H., Expression and characterization of a histidine-rich protein, Hpn: potential for Ni2+ storage in Helicobacter pylori, Biochemical Journal. 2006, 393: 285-293.

 

He M.L., Zheng B., Chen Y., Wong K.L., Huang J., Lin M.C., Peng Y., Yuen K.Y., Sung J.J. and Kung H.F., Kinetics and synergistic effects of siRNAs targeting structural and replicase genes of SARS-associated coronavirus., FEBS Letters. 2006, 580(10): 2414-2420.

 

Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785.

 

Lu L. and Huang J., Single-stranded oligonucleotide-mediated targeted gene repair in mammalian cells, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Peng Y., Yang P., Tanner J.A., Huang J., Li M., Lee H.H.F., Xu R.H., Kung H. and Lin M.C., Cold-inducible RNA binding protein is required for the expression of adhesion molecules and embryonic cell movement in Xenopus laevis, Biochem Biophys Res Commun. 2006, 344: 416-424.

 

Wang J. and Huang J., Characterization of Intracellular Transportation in KbcU-Mutant Purkinje Cells., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Wang Z. and Huang J., Mechanism study on two DNA repair systems, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Yin W.X., Wu X.S., Li Z.H., Watt R.M., Huang J., Liu D.P. and Liang C.C., Targeted correction of a chromosomal point mutation by modified single-stranded oligonucleotides in a GFP recovery system, Biochemical and Biophysical Research Communications 334 (2005) 1032-1041. 2005.

 

Zhang X., Chen B., Ng A.H.L., Tanner J.A., Tay D.K.C., So K.F., Rachel R.A., Copeland N.G., Jenkins N.A. and Huang J., Transgenic mice expressing cre-recombinase specifically in retinal rod bipolar neurons, Invest Ophthalmol Vis Sci. 2005, 46: 3515-20.

 

Researcher : Huen MSY

List of Research Outputs

 

Huen M.S.Y., A Mechanistic Study of Lambdaphage-Mediated Recombination in E. coli, PhD Thesis.. 2006.

 

Researcher : Hui KC

List of Research Outputs

 

Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Hui K.C., Ng P.K.M., Mak W.W., Jin D. and Song Y., Association of the cholesterol 24S-hydroxylase polymorphism with Alzheimer's disease in Chinese, HUGO 2006 Helsinki, Finland, 31 May-03 June 2006 . 2006.

 

Researcher : Jang BR

List of Research Outputs

 

Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42.

 

Researcher : Jim JJT

List of Research Outputs

 

Cheung K.M.C., Chen Y., Karppinen J., Chan D., Jim J.J.T., Luk K.D.K., Ala-Kokko L., Leong J.C.Y., Ott J., Sham P.C., Cheah K.S.E. and Song Y., Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in Chinese, Spine. 2006, 31(10): 1143-8.

 

Cheung K.M.C., Jim J.J.T., Noponen-Hietala N., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The Genetics of intervertebral disc degenertation, European Cells and Material: ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application. Davos, Switzerland, July . 2005.

 

Jim J.J.T., Noponen-Hietala N., Cheung K.M.C., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration, Spine. 2005, 30: 2735-2742.

 

Researcher : Jin D

Project Title:

Implementation of theoretical and technical system for disease genomics

Investigator(s):

Jin D

Department:

Institute of Molecular Biology

Source(s) of Funding:

Matching Fund for National Key Basic Research Development Scheme (973 Projects)

Start Date:

08/2001

 

Abstract:

To study implementation of theoretical and technical system for disease genomics.

 

Project Title:

Characterization of a novel centrosomal target of HTLV-I oncoprotein tax

Investigator(s):

Jin D

Department:

Institute of Molecular Biology

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

12/2001

Completion Date:

11/2005

 

Abstract:

To characterize a novel human centrosomal protein, which binds to HTLV-I oncoprotein Tax in yeast two-hybrid assay and co-immunoprecipitates with Tax from extracts of mammalian cells.

 

Project Title:

Mitotic checkpoint and genomic stability in ovarian cancer

Investigator(s):

Jin D

Department:

Biochemistry

Source(s) of Funding:

National Institutes of Health, US Department of Health and Human Services - General Award

Start Date:

09/2002

 

Abstract:

To investigate the molecular basis of mitotic checkpoint in mammalian cells nad its relevance to genomic instability in ovarian cancer.

 

Project Title:

Functional characterization of a novel liver-enriched transcription factor of the bZIP family

Investigator(s):

Jin D, Chung SK, Ching YP, Ng IOL

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

12/2002

 

Abstract:

Previous study of the research team shows that LZIP-[beta] is a liver-enriched transcription factor implicated in tissue-specific expression of genes. In this study, the team will focus on four areas of research:- 1) biochemical and biological characterization of LZIP-[beta] transcript and protein in mammalian tissues and cells; 2) functional characterization of LZIP-[beta] as a novel CRE-binding transcription factor; 3) investigating the roles of LZIP-[beta] in liver-specific gene expression and cancer development; and 4) establishment of frog and mouse models for functional studies of LZIP-[beta].

 

Project Title:

Development of RNAi technology for inhibition of viral replication

Investigator(s):

Jin D

Department:

Biochemistry

Source(s) of Funding:

Small Project Funding

Start Date:

11/2003

Completion Date:

02/2007

 

Abstract:

To use Sindbis virus as a model to systematically study RNAi-mediated inhibition of viral replication; to study the rules for selection of RNAi targets particularly effective for inhibition of viral replication in mammalian cells; to compare the effectiveness of siRNAs targeting UTR, non-structural (such as polymerase) or structural (such as capsid) regions.

 

Project Title:

Roles and regulation of peroxiredoxins: from yeast to human

Investigator(s):

Jin D

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

12/2003

 

Abstract:

To perform in-depth analyses on the transcriptional regulation of yeast PMP20; to study the structure-function relationship of yeast and human peroxiredoxins; to characterize the impact of binding to heme on Tsa1p/Tsa2p function; to investigate the roles of peroxiredoxins in cell physiology and pathology. Out focus will be on apoptosis, aging and cell proliferation.

 

Project Title:

Roles and regulation of peroxiredoxins: from yeast to human

Investigator(s):

Jin D

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

12/2003

 

Abstract:

N/A

 

Project Title:

Roles of spike protein in the pathogenesis of SARS coronavirus

Investigator(s):

Jin D, Zheng B

Department:

Biochemistry

Source(s) of Funding:

Research Fund for the Control of Infectious Diseases - Full Grants

Start Date:

02/2005

 

Abstract:

To derive novel and important insights into the molecular mechanisms for SARS-CoV pathogenesis and to reveal novel strategies for prevention as well as therapeutic interventions of SARS

 

Project Title:

Regulatory roles for vault poly(ADP-ribose) polymerase in NF[kappa]B activation

Investigator(s):

Jin D, Yam JWP

Department:

Biochemistry

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

03/2005

 

Abstract:

The main objectives of this project are: 1) To perform independent assays including co-immunoprecipitation and co-localization to verify the CIKS-VPARP interaction and to define the binding domains in the two proteins. 2) To document VPARP activation of NFkB using additional methods including EMSA and IKK assays. We will also determine the requirement for PARP activity in this activation. 3) To identify the relevant substrates or partners of VPARP that mediate its effect on NFkB.

 

Project Title:

Roles for p21-activated protein kinase 3 in HTLV-I pathogenesis

Investigator(s):

Jin D, Ching YP

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2006

 

Abstract:

To characterize the expression of Pak 3 in HTLV-I-transformed ATL cells; to study whether and how Tax induces Pak 3 expression and activity; to define the contributory roles of Pak 3 in Tax modulation of transcription and cell signaling; to assess the significance of Tax-Pak3 interaction in viral transformation and leukemogenesis.

 

Project Title:

Roles for p21-activated protein kinase 3 in HTLV-I pathogenesis

Investigator(s):

Jin D

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2006

 

Abstract:

N/A

 

Project Title:

Gene regulatory function and cellular partners of SARS-associated coronavirus nucleocapsid protein

Investigator(s):

Jin D, Zheng B, Ching YP

Department:

Biochemistry

Source(s) of Funding:

Research Fund for the Control of Infectious Diseases - Full Grants

Start Date:

02/2006

 

Abstract:

This project addressed fundamental questions on an important SARS-CoV structural protein. Our work may have implications in other aspects of SARS research. For one example, the activation of FGL2 has been thought to cause thrombosis in viral infection. Thus, elucidation of the influence of N protein on FGL2 may reveal a new mechanism for SARS-CoV pathogenesis. In addition, molecular dissection of the gene regulatory function of N protein and characterization of its cellular partners will help identify new targets for treatment. Finally, the biological systems and assays established might be used for drug screening.

 

List of Research Outputs

 

Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245.

 

Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367.

 

Chin K.T., Wong C.M., Ng I.O.L. and Jin D., Functional characterization of liver-enriched transcription factor CREB-H (poster 1989). , The American Society for Cell Biology 45th Annual Meeting, San Francisco, California, USA, December 10-14, 2005.. 2005.

 

Chin K.T., Siu Y.T., Siu K.L. and Jin D., Tax-induced recruitment of TORC family coactivators is required for transcriptional activation of the human T-cell leukemia virus type 1 long terminal repeats (invited discussant). , The Leukemia and Lymphoma Society's 2005 Stohlman Scholars Symposium, Renaissance Scottsdale Resort, Arizona, USA, September 23-24, 2005. . 2005.

 

Ching Y.P., Chan S.F. and Jin D., A centrosomal target of human T-cell leukemia virus type I oncoprotein Tax on the road to genome instability, The Croucher Advanced Study Institute “Signaling in Cell Growth abd Differentiation”. The Hong Kong University of Science and Technology, Hong Kong, January 16-20, 2006.

 

Choy E.Y.W., Kok K.H. and Jin D., Construction of New DNA Vectors Based on Promoters of Epstein-Barr Virus-Encoded Small RNAS For Expression of Small Hairpin RNAS in Mammalian Cells., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Choy E.Y.W., Kok K.H. and Jin D., Construction of new DNA vectors based on promoters of Epstein-Barr virus-encoded small RNAs for expression of small hairpin RNAs in mammalian cells., Cold Spring Harbor Laboratory 2005 Meeting on RNAi, Cold Spring Harbor, New York, USA, September 28 to October 2, 2005. . 2005.

 

Deng J., Yang Y.L., Wang L.H., Jin D. and Liang G.D., Inhibition of the replication of Sindbis virus XJ-160 by RNAi., Chinese Journal of Microbiology and Immunology. 2005, 25: 496-500.

 

Jin D., A centrosomal target of HTLV-I oncoprotein Tax on the road to genome instability., School of Life Sciences/The Biodesign Institute, Arizona State University, Tempe, Arizona, USA. September 22, 2005.. 2005.

 

Jin D., Journal of RNAi and Gene Silencing (an international journal of biology and application of RNA interference), Editorial Board. LibPubMedia, 2005.

 

Ko C.F., Yam J.W.P., Chan P.C.Y., Jin D. and Ng I.O.L., Interaction of deleted in liver cancer 1 (DLC1) with tensin2 and its implications in tumor suppression, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006.

 

Kok K.H. and Jin D., Cell to cell spreading of RNAi in mammalian cell, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Leung H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity, Proc Natl Acad Sci U S A. 2005, 102: 15207-15212.

 

Leung T.H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in Liver Cancer 2, DLC2, Suppresses Cell Transformation via Inhibition of Rhoa Activity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Li H., Fung K.L., Jin D., Chung S.S.M., Cing Y.P., Ng I.O.L., Sze K.H., Ko C.B. and Sun H., Solution structures and dynamics of the sterile of Motif (SAM) domain of the deleted in liver cancer 2 (DLC2): a monomeric structure with membrane-binding properties, Croucher Foundation Advanced Study Institute: Advances in Protein Sciences, Biochemistry Department, The Chinese University of Hong Kong, Hong Kong, 15-17 December 2005 . 2005, PO-17, p.33.

 

Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Hui K.C., Ng P.K.M., Mak W.W., Jin D. and Song Y., Association of the cholesterol 24S-hydroxylase polymorphism with Alzheimer's disease in Chinese, HUGO 2006 Helsinki, Finland, 31 May-03 June 2006 . 2006.

 

Li Y. and Jin D., Genetic Variations of the Cholesterol Metabolism Pathway Genes and the risk of Alzheimer's Disease, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Ng K.M., Mak W., Jin D., st. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese. , Dement Geriatr Cogn Disord. 2006, 22: 399-404.

 

Man C.W.Y., Rosa J., Wu Z.Q., Akira H., Jin D., Ling M.T., Cheung A., Kwong Y.L., Doxsey S. and Tsao G.S.W., ID1 Upregulates Aurora Kinase A, Induces Centrosome abnormalities, Polyploidy and Disrupts Microtubule Integrity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Man C.W.Y., Rosa J., Lee T.O., Lee H.Y.V., Chow B.K.C., Lo K.W., Doxsey S., Wu Z.G., Kwong Y.L., Jin D., Cheung A. and Tsao G.S.W., Latent membrane protein 1 suppresses RASSFIA expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells, Oncogene. 2006, 1-12.

 

Ng D.C.H., Chan S.F., Kok K.H., Yam J.W.P., Ching Y.P., Ng I.O.L. and Jin D., Mitochondrial targeting of growth suppressor protein DLC2 through the START domain, FEBS Letters . 2006, 580(1): 191-8.

 

Ng M.H., Jin D. and Chan L.C., Ras Signalling in Mll-Mediated Leukaemia, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Sze M.F., Ching Y.P., Jin D. and Ng I.O.L., Dysregulation of Mitotic Spindle Checkpoint Control in Hepatocellular Carcinomas , 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Wang X., Cheung H.W., Jin D., Ling M.T., Wong Y.C., Wang Q. and Tsao G.S.W., Effect of MAD2 expression on chemosensitivity to DNA damaging agent cisplatin in nasopharyngeal carcinoma cells., Proceeding NCRI Cancer conference, Birmingham, UK. 2005, 54.

 

Wong C.M., Yam J.W.P., Ching Y.P., Yau T.O., Leung T.H.Y., Jin D. and Ng I.O.L., Rho GTPase-Activating Protein Deleted in Liver Cancer Suppresses Cell Proliferation and Invasion in Hepatocellular Carcinoma, Cancer Research. 2005, 65: 8861-8868.

 

Wong H.L., Wang X., Chang R.C.C., Jin D., Feng H., Wang Q., Lo K.W., Huang D.P., Yuen P.W., Wong Y.C. and Tsao G.S.W., Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress., Molecular Carcinogenesis. 2005, 44: 92-101.

 

Researcher : Kok KH

List of Research Outputs

 

Choy E.Y.W., Kok K.H. and Jin D., Construction of New DNA Vectors Based on Promoters of Epstein-Barr Virus-Encoded Small RNAS For Expression of Small Hairpin RNAS in Mammalian Cells., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Choy E.Y.W., Kok K.H. and Jin D., Construction of new DNA vectors based on promoters of Epstein-Barr virus-encoded small RNAs for expression of small hairpin RNAs in mammalian cells., Cold Spring Harbor Laboratory 2005 Meeting on RNAi, Cold Spring Harbor, New York, USA, September 28 to October 2, 2005. . 2005.

 

Kok K.H. and Jin D., Cell to cell spreading of RNAi in mammalian cell, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Ng D.C.H., Chan S.F., Kok K.H., Yam J.W.P., Ching Y.P., Ng I.O.L. and Jin D., Mitochondrial targeting of growth suppressor protein DLC2 through the START domain, FEBS Letters . 2006, 580(1): 191-8.

 

Researcher : Kwok JCF

List of Research Outputs

 

Lau J.W.K., Kwok J.C.F., Ng K.Y., Chan Y.S. and Shum D.K.Y., Developing vestibular neurons display altered commissural projections with depletion of chondroitin sulfates of the hindbrain matrix, Proceedings of the 28th Annual Meeting of Japan Neuroscience Society. 2005, P3–37.

 

Researcher : Lai WL

List of Research Outputs

 

Lai W.L. and Wong N.S., Regulation of GADD153 Expression at Post-transcriptional Level by ROS, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Researcher : Lam VMS

Project Title:

Structural NADP+, subunit interaction and other stability determinants in human glucose-6-phosphate dehydrogenase (G6PD) and deficient variants

Investigator(s):

Lam VMS, Engel P.C., Adams M.J.

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

11/2000

Completion Date:

09/2005

 

Abstract:

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a global and local of jaundice in newborns. The majority are usually asymptomatic but environmental agents such as the ingestion of fava bean or some Chinese herbal medicines can induce favism or haemolysis. The project aims to bioengineer change(s) in the amino acids, around the 'structural' NADP site, some of which correspond to naturally occurring Class 1 variants.

 

Project Title:

The C-terminus of human glucose-6-phosphate dehydrogenase (h-G6PD): a structural and/or regulatory domain?

Investigator(s):

Lam VMS, Engel P.C., Adams M.J.

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

12/2002

Completion Date:

09/2005

 

Abstract:

The project aims at examining the role of the aromatic amino acids in the C-terminus. The research team will create a series of mutations in each of these residues, express and purify these enzymes for assay of stability and NADP+ binding.

 

Project Title:

'Structural' NADP+ and conformation change accompanying Glucose-6-phosphate dehydrogenase (G5PD) activity

Investigator(s):

Lam VMS, Au SWN

Department:

Biochemistry

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

01/2005

Completion Date:

09/2005

 

Abstract:

The main objectives of this project are: (1) use molecular biology techniques to create recombinant G6PD mutants at the catalytic site i.e., at His 263 and R393H & R393G near the 'structural' NADP; (2) use fluorimetric and spectrophotometric measurements to track the 'structural' NADP in mutant enzymes in (1) and compare with WT; (3) use sugar substrate analogues to form catalytically inactive enzyme-coenzyme sugar phosphate complexes. Use of this complex to assess the ability of G6P to promote reduction of the 'structural' NADP. Attempt to crystallise such enzyme ternary complexes and/or the mutant enzymes in (1).

 

List of Research Outputs

 

Researcher : Law KFS

List of Research Outputs

 

Chan D., Gao B., Hu J.X., Law K.F.S., He L. and Cheah K.S.E., Abnormal Indian Hedgehog Signaling affects Distal Digit Patterning in a Mouse Model with Brachydactyly Type A1, Frontiers in Biomedical Research, The Univeristy of Hong Kong, Hong Kong, Dec 2. 2005.

 

Researcher : Law ML

List of Research Outputs

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in Sox 10 mouse mutant, Mechanisms of Development. Elsevier, 2005, 122: S177.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in a Sox10 mouse mutant generated by gene targeting , Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the Enteric Neural Crest Development, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Law ML

List of Research Outputs

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in Sox 10 mouse mutant, Mechanisms of Development. Elsevier, 2005, 122: S177.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in a Sox10 mouse mutant generated by gene targeting , Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the Enteric Neural Crest Development, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Lee YF

List of Research Outputs

 

Lee Y.F., Identifying the inner ear specific SOX2 regulatory element(s) and SOX2 regulation of MATH1, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

 

Researcher : Leong VYL

List of Research Outputs

 

Chan D., Ho G., Leong V.Y.L. and Cheung K.M.C., The effect of severity of disc degeration on mesenchymal stem cell's ability to regenerate the intervertebral disc., European Cells and Material: ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application. Davos, Switzerland, July 2005 . 2005.

 

Cheung K.M.C., Ho G., Chan D. and Leong V.Y.L., regeneration of nucleus pulposus after disectomy by autologous mesenchymal stem cells: a rabbit model, European Cells and Material: ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application. Davos, Switzerland, July 2005 . 2005.

 

Researcher : Leung GWY

List of Research Outputs

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific Community - Stem Cells, Senescence and Cancer. Singapore, Oct 25 - Oct 30, 2005.

 

Researcher : Leung KKH

List of Research Outputs

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006.

 

Researcher : Leung WL

List of Research Outputs

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006.

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25.

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September . 2005.

 

Leung W.L., Functional Analyses of Type IIA Procollagen in Embryo Development, PhD Thesis. 2006.

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Researcher : Leung YL

Project Title:

Molecular identity of nucleus pulposus cells in intervertebral disc

Investigator(s):

Leung YL, Cheung KMC, Chan D

Department:

Orthopaedics and Traumatology

Source(s) of Funding:

Small Project Funding

Start Date:

12/2005

 

Abstract:

1) Introduction: Low back pain has been a major focus in clinical practice. It represents a world-wide health problem of which about 70-80% population will experience low back pain in their lifetime [1,6]. Intervertebral disc degeneration has been suggested to associate with low back pain and sciatica and is thought to have multi-factorial causes. Previous study in human indicated that 90% of people will develop intervertebral disc degeneration above the age of 50. However, whether the degeneration is caused by natural aging or other unknown pathological conditions is still not clear [2]. Intervertebral discs (IVD) are avascular fibrocartilagenous structures between the vertebral bodies of the spine which function to articulate the spinal motion and are subject to high mechanical loading. Degeneration of IVD is generally characterized by changes in disc morphology, composition of extracellular matrix (ECM), loss of proteoglycan and water content, and an up-regulation of metalloproteinases in IVD [2,8-10]. Nonetheless, there is a lack of consensus on the cause of degeneration. In particular, whether the degeneration is a result from a loss of mechanical integrity in the disc or the mechanical loading itself being a precipitating factor of the degeneration is still controversial [6,7]. Studies have also suggested that the degeneration is related to a change of disc cells response to mechanical stimuli [11], but the molecular events happened during the response have not been clearly elaborated. IVD consists of three components: an outer fibrous ring (annulus fibrosus, AF), an inner gelatinous filling (nucleus pulposus, NP), and cartilaginous endplates (EP) which sandwich the former two structures. During organogenesis, NP is developed from the transformation of notochord and AF is differentiated from the condensation of sclerotome, implying that IVD is derived from mesodermal origin [3,4]. IVD is populated by three major cell types: chondrocytes in EP, notochordal/chondrocyte-like cells in NP and fibroblast-like cells in AF. NP and AF contain abundant ECM, particularly collagens and proteoglycans, which are present in different proportions in the two structures [6]. Cells in IVD have been defined base on their morphology, intercellular organization, and gene expression. NP is composed of a heterogeneous cell population of interconnected cells with prominent vacuoles, which are thought to be originated from the notochord, and small chondrocyte-like cells from yet unknown origin [12]. The notochordal cells appear to be replaced with chondrocyte-like cells during IVD maturation. The replacement of cells may be possibly due to apoptosis of notochordal cells together with an invasion of chondrocytes from AF or EP, or due to differentiation of notochordal cells into chondrocytic phenotype. Study has demonstrated that degeneration is not observed in IVD where notochordal cells persist to adult age, suggesting notochordal cells play vital role in maintaining IVD integrity [21]. Among various species studied, mature sheeps, dogs, and rats are suggested to retain NP cell populations mimicking those in adult humans [12]. In situ expression of variety of genes has been studies in NP. They express chondrocyte markers such as SOX9, collagen II and IX, agreccan, decorin, TGFbeta, and Ptc [13-18]. Gene knockout in mice has demonstrated that Sox5 and Sox6 regulate NP formation while Col2a1, Pax1/Pax9, Bapx1, and Jun play regulatory roles in the development of vertebral column [4,5,19,20]. To-date, the developmental regulation and specific function of NP in IVD are still largely unknown. In particular, there have been no genes found to be specifically expressed in the notochordal cells which can define their identity and distinguish them from chondrocyte-like cells in NP. 2) Key issues and problems: There has been limited advancement in the molecular biology of prenatal and postnatal IVD. Insufficient molecular characterization of IVD cells in is one of the major obstacles in understanding the properties of IVD and the etiology of disc degeneration. The lack of knowledge in NP cell-specific genes inevitably hampers the dissection of molecular pathways related to the IVD formation, maintenance, and the cause of IVD degeneration. On the other hand, we and other groups have been working on biological therapies such as the use of bioactive molecules and stem cells to regenerate disc cells in degenerated IVD. Without sufficient knowledge in the molecular signatures of the cells, accessing the outcome of the therapies will be difficult because cell phenotype in the treated IVD cannot be adequately described. In addition, the lack of cell-specific markers also compromises the use of high-throughput screening technologies that may rely on molecular cues to report expression changes specific to IVD. Taken together, the issue is critical to both basic and applied IVD research. 3) Hypothesis and objectives: It is hypothesized that notochordal cells in NP are specialized cells for IVD function and express unique genes which determine their specific differentiation status and cellular function. This study aims to identify the genes specifically expressed in notochordal cells in NP by the use of transcriptomics and bioinformatics.

 

List of Research Outputs

 

Researcher : Li J

List of Research Outputs

 

Li J. and Cheah K.S.E., The role of Indian Hedgehog in chondrocyte hypertrophy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005.

 

Researcher : Li SKM

List of Research Outputs

 

Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785.

 

Researcher : Li X

List of Research Outputs

 

Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42.

 

Researcher : Li Y

List of Research Outputs

 

Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Hui K.C., Ng P.K.M., Mak W.W., Jin D. and Song Y., Association of the cholesterol 24S-hydroxylase polymorphism with Alzheimer's disease in Chinese, HUGO 2006 Helsinki, Finland, 31 May-03 June 2006 . 2006.

 

Li Y. and Jin D., Genetic Variations of the Cholesterol Metabolism Pathway Genes and the risk of Alzheimer's Disease, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Ng K.M., Mak W., Jin D., st. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese. , Dement Geriatr Cogn Disord. 2006, 22: 399-404.

 

Song Y., Ho W.L., Kwok H.H., Chu A.C.Y., Li Y. and Ho S.L., Genetic study of a large Chinese amyotrophic lateral sclerosis family., The 55th American society of Human Genetics meeting, October 25-29, 2005, Salt Lake City Utah, USA . 2005.

 

Researcher : Liu B

List of Research Outputs

 

Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785.

 

Researcher : Liu H

List of Research Outputs

 

Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42.

 

Researcher : Liu J

List of Research Outputs

 

Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42.

 

Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y. S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57.

 

Researcher : Liu J

List of Research Outputs

 

Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42.

 

Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57.

 

Researcher : Lo RLK

List of Research Outputs

 

Lo R.L.K., Ng V.C.W., Cheah K.S.E. and Chan D., ER-stress signaling and chondrocyte differentiation in mice, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005.

 

Researcher : Lu L

List of Research Outputs

 

Lu L. and Huang J., Single-stranded oligonucleotide-mediated targeted gene repair in mammalian cells, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Researcher : Lui VCH

Project Title:

Cre-inducible disruption of Hedgehog signaling in neural crest cell: a novel approach to study roles of Hedgehog in enteric nerous system development

Investigator(s):

Lui VCH, Tam PKH, Sham MH

Department:

Surgery

Source(s) of Funding:

Small Project Funding

Start Date:

11/2003

 

Abstract:

To generate a DNA construct for Cre-inducible expression of a Ptc1[Delta]loop2 protein; to generate transgenic mice carrying the Ptc1[Delta]loop2 DNA construct by microinjection; transgenic mice will be crossed with a vagal NCC specific Cre mouse strain; to analysis of abnormal phenotypes in the devleoping ENS of the transgenic mutant mice.

 

Project Title:

Conditional knockout of Patched gene in enteric neural crest cells: functional study of the role of Hedgehog signaling in enteric nervous system development

Investigator(s):

Lui VCH, Tam PKH, Sham MH, Hui C.C.

Department:

Surgery

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

10/2004

 

Abstract:

To cross floxed Ptc1 mice with a vagal NCC specific Cre mouse strain (b3-IIIa-cre); to analyze the abnormal phenotypes in the developing ENS of the transgenic mutant mice; to analyze the effects of mesenchyme-derived factors on NCCs of the transgenic mutant mice.

 

Project Title:

Investigation of Hoxb5 functions in enteric neurons in late gestation and neonatal period

Investigator(s):

Lui VCH, Sham MH, Tam PKH

Department:

Surgery

Source(s) of Funding:

Small Project Funding

Start Date:

11/2004

 

Abstract:

To investigate the functions of Homeobox gene Hoxb5 in enteric neurons.

 

Project Title:

Conditional knockout of Patched gene in enteric neural crest cells: functional study of the role of Hedgehog signaling in enteric nervous system development

Investigator(s):

Lui VCH

Department:

Surgery

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2005

 

Abstract:

N/A

 

Project Title:

Functional analysis of Hoxb5 in enteric neurons in mice

Investigator(s):

Lui VCH

Department:

Surgery

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

11/2005

 

Abstract:

N/A

 

Project Title:

Functional analysis of Hoxb5 in enteric neurons in mice

Investigator(s):

Lui VCH, Sham MH, Tam PKH

Department:

Surgery

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

11/2005

 

Abstract:

To analyse the expression pattern of Hoxb5 protein in enteric neurons in postnatal and adult mice; to induce the expression of en-hoxb5 in enteric neurons in late stage of ENS development and shall analyse the phenotypic consequence of the perturbation of hoxb5 function in the ENS of postnatal and adult mice.

 

List of Research Outputs

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the Enteric Neural Crest Development, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Ma RYM

List of Research Outputs

 

Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005.

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific Community - Stem Cells, Senescence and Cancer. Singapore, Oct 25 - Oct 30, 2005.

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Researcher : Ma YMR

List of Research Outputs

 

Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022.

 

Researcher : Murphy G

List of Research Outputs

 

Chan W.Y., Cheah K.S.E., Ng V.C.W., Murphy G. and Chan D., Mouse model with impaired collagen X degradation at the chondro-osseous junction, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

 

Researcher : Ng AHL

List of Research Outputs

 

Ng A.H.L., Characterization of Cre expression in BAC-Pcp2-IRES-Cre Transgenic mice, MPhil Thesis. 2005.

 

Zhang X., Chen B., Ng A.H.L., Tanner J.A., Tay D.K.C., So K.F., Rachel R.A., Copeland N.G., Jenkins N.A. and Huang J., Transgenic mice expressing cre-recombinase specifically in retinal rod bipolar neurons, Invest Ophthalmol Vis Sci. 2005, 46: 3515-20.

 

Researcher : Ng DCH

List of Research Outputs

 

Ng D.C.H., Chan S.F., Kok K.H., Yam J.W.P., Ching Y.P., Ng I.O.L. and Jin D., Mitochondrial targeting of growth suppressor protein DLC2 through the START domain, FEBS Letters . 2006, 580(1): 191-8.

 

Researcher : Ng VCW

List of Research Outputs

 

Chan W.Y., Cheah K.S.E., Ng V.C.W., Murphy G. and Chan D., Mouse model with impaired collagen X degradation at the chondro-osseous junction, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

 

Lo R.L.K., Ng V.C.W., Cheah K.S.E. and Chan D., ER-stress signaling and chondrocyte differentiation in mice, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005.

 

Researcher : Ott J

List of Research Outputs

 

Cheung K.M.C., Jim J.J.T., Noponen-Hietala N., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The Genetics of intervertebral disc degenertation, European Cells and Material: ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application. Davos, Switzerland, July . 2005.

 

Researcher : Poon WH

List of Research Outputs

 

Wong N.S. and Poon W.H., The Kappa-opioid receptor specific agonist U50488H induces mitochondrial stress in cultured human cancer cells., The FEBS Journal (formerly European Journal of Biochemistry). 2005, 272, Supplement 1: n5-029p.

 

Researcher : Sae-Pang JJ

List of Research Outputs

 

Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Sham MH

Project Title:

Hoxb3lacZ: a mutant mouse model for studying the roles of Hoxb3 in heart and thoracic body wall development

Investigator(s):

Sham MH

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2003

 

Abstract:

To characterize the Hoxb3(lacZ) mutant locus and examine if this is a hypomorphic mutant; to analyse the cardiac abnormalities in the Hoxb3(lacZ) mutant using molecular markers and determine the role of Hoxb3 during heart development; to examine the ventral body wall defect by morphological and molecular markers, and identify any cooperation of Hoxb3 with other Hox genes in the developmental processes involved.

 

Project Title:

Hoxb3lacZ: a mutant mouse model for studying the roles of Hoxb3 in heart and thoracic body wall development

Investigator(s):

Sham MH

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

09/2003

 

Abstract:

N/A

 

Project Title:

Investigating the molecular basis of Sox10 functions in enteric nervous system development using a series of mutant mouse models

Investigator(s):

Sham MH

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

09/2005

 

Abstract:

N/A

 

List of Research Outputs

 

Cai K., Xu R. and Sham M.H., Adeno-associated virus vector-mediated angiogenic inhibitors suppress lung tumor growth in mice., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005.

 

Kong C.T., Sham M.H. and Chan L.C., The MLL-EEN fusion gene leads to maturation arrest and self-renewal of hematopoietic progenitors in ES cells and the development of myeloid leukemia in chimeric mice, FASEB Summer Research Conferences - Hematological Malignancies, Saxtons River, USA. July 30 - August 4, 2005 . 2005.

 

Kong C.T., Sham M.H., So C.W.E., Cheah K.S.E., Chen S.J. and Chan L.C., The Mll-Een knockin fusion gene enhances proliferation of myeloid progenitors derived from mouse embryonic stem cells and causes myeloid leukaemia in chimeric mice, Leukemia. 2006, 20: 1829–1839.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in Sox 10 mouse mutant, Mechanisms of Development. Elsevier, 2005, 122: S177.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in a Sox10 mouse mutant generated by gene targeting , Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the Enteric Neural Crest Development, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Lui V.C.H., Fu M., Poon H.C., Sham M.H., Pachnis V., Hui C.C. and Tam P.K.H., Conditional knockout of PTC1 gene in vagal neural crest cells causes defective ENS development in mice, Development of the Enteric Nervous System: Cells, signals and genes, New York, U.S.A., 26-29 March 2006. 2006.

 

Lui V.C.H., Cheng W.C., Chen Y., Sham M.H. and Tam P.K.H., Homeobox gene HOXB5 is required in the embryonic development of the enteric nervous system, 52nd Annual International Congress of British Association of Paediatric Surgeons, Dublin, Ireland, 12-15 July 2005.

 

Lui V.C.H., Cheng W.C., Chen Y., Sham M.H. and Tam P.K.H., Perturbation of Hoxb5 signalling in vagal neural crest cells causes defective development of the enteric nervous system, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September 2005.

 

Lui V.C.H., Cheng W.C., Chen Y., Sham M.H. and Tam P.K.H., Perturbation of Hoxb5 signalling in vagal neural crest cells causes defective development of the enteric nervous system, Mechanisms of Development. 2005, 122: S93.

 

Ngan E.S.W., Lui V.C.H., Lau K.C., Garcia-Barcelo M.M., Sham M.H. and Tam P.K.H., Transcriptional profiling of enteric neural crest cells, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Sham M.H., Ectopic expression of Hoxb3 in the mouse hindbrain causes abnormal ear development, The 15th International Society of Development Biologists Congress, Sydney, Australia. 2005.

 

Sham M.H., Sox10 mutations and enteric nervous system development, Department of Anatomy and Cell Biology, University of Melbourne, Australia. 2005.

 

Siu K.Y., Sham M.H. and Chow B.K.C., Secretin is widely expressed during mouse embryonic development, 7th International Symposium on VIP, PACAP and Related Peptides, Rouen, France.. 2005.

 

Siu K.Y., Sham M.H. and Chow B.K.C., Secretin is widely expressed during mouse embryonic development, Regulatory Peptides. 2006, 130(3): 176.

 

Siu K.Y., Sham M.H. and Chow B.K.C., The prenatal expression of secretin receptor, Annals New York Academy of Sciences. 2006, 1070: p561-565.

 

Wong E.Y.M., Chan Y.S., Wu D.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in mouse hindbrain causes abnormal ear development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September . 2005.

 

Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia . 2005.

 

Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Hoxb3 is involved in the endothelin-1 signaling pathway in patterning the facial branchial arches, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005.

 

Wong P.M., Lu L. and Sham M.H., HOXB3 Mutation Generated By Gene Targeting Leads to Plasmacytoma, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Xu R., Ma H., Li H., Sham M.H., Li E.T.S., Tam P.K.H. and Lam K.S.L., Oral viral vector gene delivery, In: Redberry GW (ed). Trends in Gene Therapy Research. New York, U.S.A., Nova Sciecen Publishers, Inc., 2005, 191-221.

 

Researcher : Sham PC

Project Title:

An association screen for schizophrenia susceptibility loci in a high-LD, gene-rich region of chromosome 3p

Investigator(s):

Sham PC

Department:

Psychiatry

Source(s) of Funding:

Small Project Funding

Start Date:

07/2004

 

Abstract:

To identify novel susceptibility loci for schizophrenia, by conducting a high-density SNP screen of a region recently identified by a meta-analysis of 20 genome-wide linkage scans.

 

Project Title:

A systematic screen for schizophrenia susceptibility loci in high-LD, gene-rich chromosomal regions implicated by meta-analysis of whole genome linkage scans

Investigator(s):

Sham PC

Department:

Psychiatry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2006

 

Abstract:

N/A

 

Project Title:

A systematic screen for schizophrenia susceptibility loci in high-LD, gene-rich chromosomal regions implicated by meta-analysis of whole genome linkage scans

Investigator(s):

Sham PC, Chen RYL, Ng KP, Li T

Department:

Psychiatry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2006

 

Abstract:

To identify novel susceptibility loci for schizophrenia, by conducting a high-density SNP screen of a number of chromosomal regions that are (a) identified as linkage hotspots by a recent meta-analysis of 20 genome-wide scans of schizophrenia, (b) gene-rich and (c) high in the level of linkage disequilibrium (LD). Optimal marker sets that tag all common variation in these regions will be selected using HapMap data on the Chinese population. These regions will be screened in 489 cases of DSM-IV schizophrenia and 520 controls recruited from Hong Kong; significant associations will be replicated on 500 cases and both parents recruited from Chengdu.

 

List of Research Outputs

 

Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S.P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on familial Early-onset Degenerative Disc Disease(DDD), Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland.. 2006.

 

Researcher : Shum DKY

Project Title:

Expression of heparanase in the injured spinal cord

Investigator(s):

Shum DKY

Department:

Biochemistry

Source(s) of Funding:

Small Project Funding

Start Date:

11/2003

 

Abstract:

To determine the time course and cellular source of heparanase expression in the bridged hemicord; to determine the distribution of substrate HS in relation to the heparanase-expressing cells.

 

Project Title:

Expression of chondroitin sulfotransferases in the injured spinal cord

Investigator(s):

Shum DKY

Department:

Biochemistry

Source(s) of Funding:

Small Project Funding

Start Date:

11/2004

 

Abstract:

To determine the expression profiles of the chondroitin sulfotransferases (STs) with time; to map the expression of chondroitin STs in reactive astrocytes, macrophages and meningeal fibroblasts that invade the leison site; to recover chondroitin sulfates of the lesion site and surrounding glial scar for comparison of sulfation patterns with those of intact tissue.

 

Project Title:

Chondroitin sulfates regulate axonal growth and patterning in the developing hindbrain

Investigator(s):

Shum DKY

Department:

Biochemistry

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

 

Chan C.H., Ip M.S.M. and Shum D.K.Y., Heparan Sulfate/Syndecan-1 Modulates the Balance between Proteinase and Anti-Proteinase in Bronchiectasis, Proteoglycans in Signaling Stockholm (Runo), Sweden, September 7-11,2005.

 

Chen L.W., Tse Y.C., Li C., Guan Z.L., Lai C.H., Yung K.K.L., Shum D.K.Y. and Chan Y.S., Differential expression of NMDA and AMPA/KA receptor subunits in the inferior olive of postnatal rats. , Brain Research. 2006, 1067(1): 103-114.

 

Lai S.K., Lai C.H., Yung K.K., Shum D.K.Y. and Chan Y.S., Maturation of otolith-related brainstem neurons in the detection of vertical linear acceleration in rats. , Eur J Neurosci.. 2006, 23(9): 2431-46.

 

Lau J.W.K., Kwok J.C.F., Ng K.Y., Chan Y.S. and Shum D.K.Y., Developing vestibular commissural projections display differential patterns with chondroitinase treatment of the hindbrain, Society for Neuroscience Abstract (U.S.A.). 2005, 481.8.

 

Lau J.W.K., Kwok J.C.F., Ng K.Y., Chan Y.S. and Shum D.K.Y., Developing vestibular neurons display altered commissural projections with depletion of chondroitin sulfates of the hindbrain matrix, Proceedings of the 28th Annual Meeting of Japan Neuroscience Society. 2005, P3–37.

 

Li C., Zhang Y. K., Guan Z.L., Shum D.K.Y. and Chan Y.S., Vestibular afferent innervation in the vestibular efferent nucleus of rats. , Neurosci Lett.. 2005, 385(1): 36-40.

 

Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42.

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Expression of heparanase in newborn mouse growth plates, Glycoconjugate Journal, GlycoXVIII, XVIII International Symposium on Glycoconjugates, Firenze, Italy. 2005.

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan Sulfates and Heparanase in the Mineralizing Matrix of Developing Mouse Growth Plate., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan sulfates and heparanase at the mineralization front of the developing growth plate., Proteoglycans in Signaling, Stockholm (Runo), Sweden, September 7-11,2005.

 

Zhang F.X., Lai C.H., Tse Y.C., Shum D.K.Y. and Chan Y.S., Expression of Trk receptors in otolith-related neurons in the vestibular nucleus of rats., Brain Research. 2005, 1062(1-2): 92-100.

 

Zhang F.X., Lai C.H., Li J.L., Shum D.K.Y. and Chan Y.S., Tyrosine kinase receptor immunoreactivity in trigeminal mesencephalic and motor neurons following transection of masseteric nerve of the rat. , Neuroscience. 2006, 139(3): 921-30.

 

Zhang Y. and Shum D.K.Y., Functional Study of Heparanase in the explant cultures of rat dorsal root ganglia., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57.

 

Researcher : Siu KL

List of Research Outputs

 

Chin K.T., Siu Y.T., Siu K.L. and Jin D., Tax-induced recruitment of TORC family coactivators is required for transcriptional activation of the human T-cell leukemia virus type 1 long terminal repeats (invited discussant). , The Leukemia and Lymphoma Society's 2005 Stohlman Scholars Symposium, Renaissance Scottsdale Resort, Arizona, USA, September 23-24, 2005. . 2005.

 

Researcher : Siu YT

List of Research Outputs

 

Chin K.T., Siu Y.T., Siu K.L. and Jin D., Tax-induced recruitment of TORC family coactivators is required for transcriptional activation of the human T-cell leukemia virus type 1 long terminal repeats (invited discussant). , The Leukemia and Lymphoma Society's 2005 Stohlman Scholars Symposium, Renaissance Scottsdale Resort, Arizona, USA, September 23-24, 2005. . 2005.

 

Researcher : Smith DK

Project Title:

Patterns in proteins with unusual flexibility profiles

Investigator(s):

Smith DK

Department:

Biochemistry

Source(s) of Funding:

Seed Funding for New Staff

Start Date:

08/2002

 

Abstract:

To identify what makes some proteins imcompatible with flexibility parameters calculated from a large set of protein structures.

 

List of Research Outputs

 

Cai J.J., Smith D.K., Xia X. and Yuen K.Y., MBEToolbox 2.0: an enhanced version of a Matlab toolbox for Molecular Biology and Evolution., Evolutionary Bioinformatics Online. 2006, 2: 187-190.

 

Fu W., Chung B.H.Y., Smith D.K. and Cheung P.T., Automated method for the identification of conserved non-coding regions in hypoxic-ischaemic regulated genes in different species, DK 50th Anniversary Symposium on Paediatric Neurology and Neuro-Rehabilitation, 16-17 September 2005.

 

Fu W., Chung B.H.Y. and Smith D.K., Bioinformatic Pipeline for the Identification of Transciption Factor Binding Sites in Mouse and Human, Human Genome Meeting (HGM) 2006, Helsinki, Finland, 31 May - 3 June 2006. 59.

 

Fu W., Chung B.H.Y., Smith D.K. and Cheung P.T., Bioinformatic piepline for the identification of transcription factor binding sites in mouse and human, Joint 6th Human Genome Organization (HUGO) Pacific Meeting & 7th Asia-Pacific Human Genetics Conference (HUGO-AP 2006), Taipei, Taiwan, 6-10 March 2006. 93.

 

Fu W., Chung B.H.Y., Smith D.K. and Cheung P.T., Bioinformatic pipeline for the identification of transcription factor binding sites in mouse and human, Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association, Queen Elizabeth Hospital, 7 January 2006. 58.

 

Fu W., Chung B.H.Y., Chan K.W., Bhatia I., Smith D.K. and Cheung P.T., Sequence analysis for putative transcription factor binding sites of a novel hypoxic-ischaemic regulated gene - HID-1, Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association, Queen Elizabeth Hospital, 7 January 2006. 61.

 

Fu W., Chung B.H.Y., Chan K.W., Bhatia I., Smith D.K. and Cheung P.T., Sequence analysis of putative promoter sequences of known and novel genes identified by hpoxic-ischaemic insult, 10th Research Postgraduate Symposium , Faculty of Medicine, HKU, 3 December 2005. 118.

 

He W., Gong K., Smith D.K. and IP N.Y., The N-terminal cytokine binding domain of LIFR is required for CNTF binding and signaling ., FEBS Letters. 2005, 579: 4317-4323.

 

Researcher : So CL

List of Research Outputs

 

Chan D., Tsang K.Y., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B., Yamada Y., Bateman J.F., Cheung K.M.C. and Cheah K.S.E., Endoplasmic reticulum stress and reprogramming of hypertrophic chondrocytes, Gordon Research Conference: Collagen. New London, New Hampshire USA, July. 2005.

 

Tsang K.Y., Chan D., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B., Yamada Y., Bateman J.F., Cheung K.M.C. and Cheah K.S.E., Chondroctes Alleviate ER Stress Caused by Unfolded Proteins by Reprogramming, The British Society for Matrix Biology. 25th Anniversary Meeting Pathobiology of Bone and Cartilage. Manchester, UK, 12-13 September . 2005.

 

Researcher : Song Y

Project Title:

Genetic linkage analysis of early onset degenerative disc disease in Southern Chinese

Investigator(s):

Song Y, Cheah KSE, Cheung KMC, Leong JCY, Chan D

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

11/2003

 

Abstract:

To detect linkage associated with early onset familial DDD by performing a genome-wide scan; to define the chromosomal location of the early onset familial DDD gene; to begin preliminary work towards positional/candidate clonning.

 

Project Title:

Genetic linkage analysis of early onset degenerative disc disease in Southern Chinese

Investigator(s):

Song Y, Cheah KSE, Cheung KMC, Leong JCY, Chan D

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

11/2003

 

Abstract:

N/A

 

Project Title:

Genetic study of Alzheimer disease in Chinese

Investigator(s):

Song Y, Sham PC, Chu LW

Department:

Genome Research Centre

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

01/2005

Completion Date:

06/2006

 

Abstract:

The main objectives of the project are: 1) To establish the methodology for genome-wide association analysis using pooled DNA samples and the Affymetrix 100k GeneChip at the Genome Research Centre, so that this can be provided as a service to investigators. 2) To detect novel susceptibility loci for Alzheimer's disease using this methodology.

 

Project Title:

Mapping and cloning a new gene on chromosome 8q24 for amyotrophic lateral sclerosis in a large Chinese family

Investigator(s):

Song Y

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2005

 

Abstract:

N/A

 

Project Title:

Mapping and cloning a new gene on chromosome 8q24 for amyotrophic lateral sclerosis in a large Chinese family

Investigator(s):

Song Y, Ho SL, Fong CY, Ramsden D.B.

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2005

 

Abstract:

Biomarkers detection; detection possible ALS modifier on chromosome 10 in Branch A; longitudinal follow-up of both branches; mapping the CMT II locus in Branch B.

 

Project Title:

Mapping a genetic modifier for heart defects in Type IIA procollagen deficient mutant mice

Investigator(s):

Song Y

Department:

Genome Research Centre

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2006

 

Abstract:

N/A

 

Project Title:

Mapping a genetic modifier for heart defects in Type IIA procollagen deficient mutant mice

Investigator(s):

Song Y, Cheah KSE, Sham PC

Department:

Genome Research Centre

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2006

 

Abstract:

To perform a genome-wide scan using mouse microsatellite markers to map the modifer locus to within a 20cM region; to generate region-specific speed modifer congenic mice for fine mapping of this 20cM region; to map the modifier locus to a 1cM region and combine with the results of gene expression in the modifier region to provide the essential genetic resources for future studies aimed at precise identification of the modifier gene.

 

List of Research Outputs

 

Chai L., Leung W.K., Zee K.Y. and Song Y., Association Between Genetic Polymorphisms and Periodontitis In Hong Kong Population., A Preliminary Report. 84th International association for Dental Research, June 28 - July 1, 2006, Brisbane, Australia. 2006.

 

Cheung K.M.C., Chen Y., Karppinen J., Chan D., Jim J.J.T., Luk K.D.K., Ala-Kokko L., Leong J.C.Y., Ott J., Sham P.C., Cheah K.S.E. and Song Y., Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in Chinese, Spine. 2006, 31(10): 1143-8.

 

Cheung K.M.C., Jim J.J.T., Noponen-Hietala N., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The Genetics of intervertebral disc degenertation, European Cells and Material: ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application. Davos, Switzerland, July . 2005.

 

Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S.P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on familial Early-onset Degenerative Disc Disease(DDD), Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland.. 2006.

 

Jim J.J.T., Noponen-Hietala N., Cheung K.M.C., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration, Spine. 2005, 30: 2735-2742.

 

Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Hui K.C., Ng P.K.M., Mak W.W., Jin D. and Song Y., Association of the cholesterol 24S-hydroxylase polymorphism with Alzheimer's disease in Chinese, HUGO 2006 Helsinki, Finland, 31 May-03 June 2006 . 2006.

 

Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Ng K.M., Mak W., Jin D., st. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese. , Dement Geriatr Cogn Disord. 2006, 22: 399-404.

 

Meng Y., Rogaeva E., Lee J.H., Gu Y.J., Kawarai T., Katayama T., Erlich P., Baldwin C.T., Cheng R., Hasegawa H., Chen F., Shibata N., Lunetta K.L., Cupples L.A., Song Y., Fraser P.E., Westaway D., Mayeux R., Farrer L.A. and St. George-Hyslop P., The sortilin-related recentor SORLA is functionally and genetically associated with Alzheimer Disease., The 55th american society of Human Genetics meeting. October25-29, 2005, Salt Lake City Utah. 2005.

 

Ng M.C., Ho J.T., Ho S.L., Lee R., Li G., Song Y., Chan K.H., Cheng T.S., Yang E.S. and Leong L.Y., Asymptomatic members with SOD1 mutation in a large kindred with familial amyotrophic lateral sclerosis have abnormal water diffusion characterisitcs., The International Society for Magnetic Resonance in Medicine (ISMRM2006). 6-12 May 2006, Seattle, Washington, USA. 2006.

 

Song Y., Ho D.W.H., Cheung K.M.C., Karppinen J., YIP S.P., Leong J.C.Y., Ott J., Luk K.D.K., Cheah K.S.E., Sham P.C. and Chan D., Genetic Linkage analysis of early onset degenerative disc disease in Southern Chinese., HUGO Pacific meeting & Asia-pacific Human Genetics Conference (HUGO-AP 2006), March 6-10, 2006 Academica Sinica, Taipei. 2006.

 

Song Y., Ho W.L., Kwok H.H., Chu A.C.Y., Li Y. and Ho S.L., Genetic study of a large Chinese amyotrophic lateral sclerosis family., The 55th American society of Human Genetics meeting, October 25-29, 2005, Salt Lake City Utah, USA . 2005.

 

Tang L.F., Chan S.Y., Sham P.C. and Song Y., In silico mapping of quantitative trait loci affecting bone mineral density in mice., HUGO Pacific meeting & Asia-Pacific Human Genetics Conference (HUGO-AP 2006) March 6-10,2006 Academica Sinica, Taipei. 2006.

 

Tsui L.C., Mak W., Sham P.C., Song Y. and Tam P.K.H., Haplotype Map of the Human Genome, Nature . 2005, 437: 1299-1320.

 

Researcher : Tai CP

List of Research Outputs

 

Tai C.P., An In VivoAnalysis of Specificity of Gene Transactivation by SOX Proteins, PhD Thesis. 2006.

 

Researcher : Tam PKH

Project Title:

Transgenesis animals as bioreactors: production of a new immunosuppressive protein CTLA4Ig by transgenesis

Investigator(s):

Tam PKH, Wong NS, Cheah KSE, Dallman M.J., Sun F.Z.

Department:

Surgery

Source(s) of Funding:

Vice-Chancellor's Office - General Award

Start Date:

07/1997

 

Abstract:

The use of transgenic farm animals as bioreactors is a potentially powerful and important new industry for the next century. This application of transgenic technology, in combination with the recent advance in ability to clone animals from adult cells, enhances the potential of transgenic animal bioreactors as major producers of therapeutic proteins. Therefore by initiating research in this area there are immediate and long-term benefits to Hong Kong and China.

 

Project Title:

Establishing a "train-the-trainers" programme for paediatric surgery in China

Investigator(s):

Tam PKH, Lin CL

Department:

Surgery

Source(s) of Funding:

S.K. Yee Medical Foundation - General Award

Start Date:

10/1998

 

Abstract:

To improve the standard of surgical care of children in China through the establishment of a scheme of "train-the-trainers"; to improve our understanding of special paediatric surgical issues relevant to the Chinese population (e.g. disease patterns, transferability of western "advances" to China etc.) through systematic exchanges with major centres in China and hence enhance our ability to deliver better surgical care to children in Hong Kong.

 

Project Title:

Expanding the "Train-the-Trainers" programme for paediatric surgery in China

Investigator(s):

Tam PKH, Lin CL, Zhang J.Z., Wang W.L., Shi C.R.

Department:

Surgery

Source(s) of Funding:

S.K. Yee Medical Foundation - General Award

Start Date:

10/2000

 

Abstract:

To improve the standard of surgical care of children in China through the consolidation and expansion of a scheme of "Train-the-Trainers"; to improve our understanding of special paediatric surgical issues relevant to the Chinese population (e.g. disease patterns, transferability of western "advances" to China etc) through systematic exchanges with major centres in China and hence enhance our ability to deliver better surgical care to children in Hong Kong; to promote modern concepts of medical education among leaders of the new generation of doctors through the introduction of structured training, problem-based learning, life-long learning, and the use of evidence-based medicine and information technology.

 

Project Title:

Sonic hedgehog signalling in chronic allograft rejection

Investigator(s):

Tam PKH, Tian L, Dallman M.J., Lamb J.R.

Department:

Surgery

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2002

Completion Date:

08/2005

 

Abstract:

To investigates the role of Notch, Sonic hedgehog (Shh) signalling in acute and chronic graft rejection in a rat model of small bowel transplantation; to study if the blockade of Shh signalling alone or in conjunction with the use of TFG-[beta] inhibitors can ameliorate chronic rejection.

 

Project Title:

The role of sonic hedgehog in immune system

Investigator(s):

Tam PKH, Tian L, Chan VSF, Lamb J.R.

Department:

Surgery

Source(s) of Funding:

Other Funding Scheme

Start Date:

10/2002

 

Abstract:

To elucidate the role of sonic hedgehog in CD4+ T cells activation and to identify its downstream targets suring T cell activation.

 

Project Title:

Improving the survival and quality of life of children with cancers in China

Investigator(s):

Tam PKH, Wong IHN, Chan GCF, Ren Y, Lin CL, Li Z.Z., Zhang J.Z., Wang W.L., Shi C.R.

Department:

Surgery

Source(s) of Funding:

S.K. Yee Medical Foundation - General Award

Start Date:

10/2003

 

Abstract:

To improve the survival and quality of life of poor and sick children suffering from cancer through the establishment of a Chinese Children Cancer Consortium which will be responsible for the introduction and implementation of modern, comprehensive management protocols, and for training and educating health care workers around the country to adopt the new standard of cares for children with cancer.

 

Project Title:

The study of co-stimulatory function of sonic hedgehog in CD4+ lymphocytes

Investigator(s):

Tam PKH, Chan VSF, Lamb J.R.

Department:

Surgery

Source(s) of Funding:

Small Project Funding

Start Date:

11/2003

 

Abstract:

To study the distribution of Shh and its receptors on the surface of T cells during T cell activation; to study the effect of Shh on TH1 and TH2 cell differentiation; to identify the downstream targets of Shh signaling pathway in CD4+ T lymphocytes.

 

Project Title:

Evaluation of HOXB5 as a new Hirschprung's disease susceptibility locus

Investigator(s):

Tam PKH, Lui VCH, Garcia-Barcelo MM

Department:

Surgery

Source(s) of Funding:

Small Project Funding

Start Date:

11/2004

 

Abstract:

To evaluate the human HOXB5 gene as a new Hirschsprung's disease susceptibility locus.

 

Project Title:

Further expansion of the "Train-the-Trainers" programme for paediatric surgery in China

Investigator(s):

Tam PKH, Wong KKY, Chan KL, Yip KF, Wang W.L., Shi C.R., Zhang J.Z., Zhan JH, Jin XQ

Department:

Surgery

Source(s) of Funding:

S.K. Yee Medical Foundation - General Award

Start Date:

05/2005

 

Abstract:

The project aims to improve the standard of surgical care of children in China; to improve understanding of special paediatric surgical issues relevant to the Chinese population; and to promote modern concepts of medical education among leaders of the new generation of doctors in China.

 

Project Title:

University strategic research theme: Genomics, Proteomics & Bioinformatics

Investigator(s):

Tam PKH, Leung FCC, Chen SF, Che CM, He Q, Ng KP

Department:

Surgery

Source(s) of Funding:

Seed Funding for Strategic Research Theme

Start Date:

05/2005

 

Abstract:

To facilitate multidisciplinary research in the areas of genomics, proteomics and bioinformatics. The three subthemes would be created, and an additional subtheme on thical, legal and social issues (ELSI) should be created.

 

List of Research Outputs

 

Tsui L.C., Mak W., Sham P.C., Song Y. and Tam P.K.H., Haplotype Map of the Human Genome, Nature . 2005, 437: 1299-1320.

 

Researcher : Tam PPL

List of Research Outputs

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25.

 

Researcher : Tam S

List of Research Outputs

 

Cheung Y.F., Karmin O., Tam S. and Siow Y.L., Induction of MCP1, CCR2, and iNOS Expression in THP-1 Macrophages by Serum of Children Late After Kawasaki Disease, Pediatric Research. 2005, 58(6): 1306-1310.

 

Cheung Y.F., Karmin O., Tam S. and Siow Y.L., MCP1, CCR2 and iNOS Induction in THP-1 Macrophages by Serum of Children Late After Kawasaki Disease, 1st Congress of Asian Society for Pediatric Research, Tokyo, Japan, 24-26 November 2005. 91.

 

Researcher : Tam SMT

List of Research Outputs

 

Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022.

 

Researcher : Tam TSM

List of Research Outputs

 

Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005.

 

Researcher : Tang LF

List of Research Outputs

 

Tang L.F., Chan S.Y., Sham P.C. and Song Y., In silico mapping of quantitative trait loci affecting bone mineral density in mice., HUGO Pacific meeting & Asia-Pacific Human Genetics Conference (HUGO-AP 2006) March 6-10,2006 Academica Sinica, Taipei. 2006.

 

Researcher : Tanner JA

Project Title:

Comparative Characterization of the Two Polyphosphate Kinases of M. tuberculosis

Investigator(s):

Tanner JA

Department:

Biochemistry

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

02/2005

 

Abstract:

Inorganic polyphosphate (polyP) is present in every cell in nature and consists of chains of tens or hundreds of orthophosphate residues linked by high-energy phospoanhydride bonds. For decades, the molecule was ignored as a 'molecular fossil', but recent discoveries, principally by Nobel Prize winner Arthur Kornberg, have challenged this view and brought deserved attention to this forgotten biopolymer [1]. In prokaryotes, the molecule plays a critical role in physiological adjustments to growth, development, stress and deprivation [2], besides acting as a phosphate reservoir, a metal chelator, a buffer, and is an important factor in mRNA processing and degradadation. In eukaryotes, roles have only started to be uncovered in the last year or two, but the molecule has already been shown to be a regulatory factor in the proliferative signaling pathways of mammalian cells [3]. It is clear that this simple inorganic molecule plays fundamental and crucial roles that are only just beginning to be unravelled. Until 2002, it was believed that polyphosphates were synthesized by a single class of enzymes, the polyphosphate kinases (PPK). However, a landmark paper from Kornberg in 2002 challenged that view [4], and it was discovered that there are in fact two classes of polyphosphate synthetases in prokaryotes: PPK1 and PPK2. Some bacteria, such as E. coli and H. pylori, only possess PPK1, others, such as M. tuberculosis, have both PPK1 and PPK2, whilst a few others only have PPK2. As PPK1 and PPK2 only exist in microorganisms and are absolutely absent from higher eukaryotes, these are excellent targets for new classes of antibacterials. As a first step towards both new antibacterials against tuberculosis and to deepen our understanding of this fundamental class of enzymes, we here propose to purify and perform a comparative characterization of PPK1 and PPK2 from M. tuberculosis. We shall test the emerging hypothesis that PPK1 is primarily a Mg2+-dependent ATP driven kinase whilst PPK2 is primarily a Mn2+-dependent GTP driven kinase. If this hypothesis holds true, it carries significant insight into the relationship between inorganic polyphosphate and the cell cycle.We can break down the overall objectives of this seed project funding grant into a three-stage process:I. Cloning of the ppk1 and ppk2 genes from M. tuberculosis.II. Purification of the PPK1 and PPK2 proteins.III. Comparative enzymatic characterization of PPK1 and PPK2.1. Kornberg, A., N. N. Rao, et al. (1999). "Inorganic polyphosphate: a molecule of many functions." Annu Rev Biochem 68: 89-125.2. Kuroda, A., K. Nomura, et al. (2001). "Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E. coli." Science 293(5530): 705-8.3. Wang, L., C. D. Fraley, et al. (2003). "Inorganic polyphosphate stimulates mammalian TOR, a kinase involved in the proliferation of mammary cancer cells." Proc Natl Acad Sci U S A 100(20): 11249-54.4. Zhang, H., K. Ishige, et al. (2002). "A polyphosphate kinase (PPK2) widely conserved in bacteria." Proc Natl Acad Sci U S A 99(26): 16678-83.

 

Project Title:

Evolution, validation and delivery of aptamer-based inhibitors that target the SARS coronavirus

Investigator(s):

Tanner JA

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

10/2005

 

Abstract:

N/A

 

Project Title:

Evolution, validation and delivery of aptamer-based inhibitors that target the SARS coronavirus

Investigator(s):

Tanner JA, Miller A, Huang J, Kao RYT

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

10/2005

 

Abstract:

Development of effective aptamer-based inhibitors of the SARs coronavirus.

 

Project Title:

Mechanistic Insight into Polyphosphate Kinase 2 - a Fundamental Enzyme of Polyphosphate Catabolism

Investigator(s):

Tanner JA

Department:

Biochemistry

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

04/2006

 

Abstract:

Long polyphosphate chains were long thought to be irrelevant to biology and to be a by-product of metabolism, but recent discoveries have overhauled this view and have refocused attention on these fundamental simple molecules [1]. Polyphosphates act in prokaryotes as a control of growth, development, stress, an energy source, a buffer, a metal chelator, and play a role in RNA processing [2]. Perhaps even more significantly, in eukaryotes the molecules have been identified as being critical to certain proliferative signalling pathways of mammalian cells [3]. Two classes of enzymes have been discovered that synthesise these molecules from ATP – polyphosphate kinase 1 (PPK1) and polyphosphate kinase 2 (PPK2) [4]. Polyphosphates are simple and fundamental molecules, yet their roles remain poorly investigated, despite the possibility that structural and functional variation as introduced by branching could result in a completely new class of informational biological macromolecule. Last year, our team was awarded a grant from the Seed Funding for Basic Research scheme entitled “Comparative Characterisation of the Two Polyphosphate Kinases of M. tuberculosis”. The aim of that grant was to clone, purify and characterise PPK1 and PPK2 from Mycobacterium tuberculosis (MTB) with a view to drug development by inhibiting these enzymes (in a follow-up RGC grant application). Our initial hypothesis was that PPK1 was an ATP-driven and Mg2+-dependent polyphosphate kinase, whilst PPK2 was a GTP-driven and Mn2+-dependent polyphosphate kinase. Our research for that grant was successful in that we were able to test the hypothesis, but we actually found that PPK2 was far more effective in catalysing the reverse reaction of hydrolysing long-chain polyphosphate in the presence of GDP. This suggests a novel mechanism for forming energy rich nucleoside triphosphates (and possible tetraphosphates), and is a fascinating departure from our initial hypothesis. However, this opens up many fascinating questions but unfortunately meant that our research was premature for submission to the RGC in the 2005 round. With a view to submitting this research in the 2006 RGC round, here, our overall objective is to strengthen our hypothesis that PPK2 provides a novel route to nucleoside triphosphates from long-chain polyphosphates. We will achieve our objective in three stages: 1. Investigate whether GTP or Gp4 is generated during PPK2 mediated polyphosphate hydrolysis. At present, we use a gel-based assay that enables us to observe changes in polyphosphate chain length. It remains unclear whether phosphate or pyrophosphate is transferred to GDP, and hence whether GTP or Gp4 is generated during the reaction. This is essential mechanistic information prior to observing the details of the kinetics of PPK2 in stage 2. 2. Measure the precise kinetics of GTP/Gp4 formation and polyphosphate catabolism by PPK2 We will use various assays to examine the efficacy of GTP/Gp4 synthesis and the rates of polyphosphate catabolism, and compare these to published kinetic data for polyphosphate formation by PPK1. 3. Measure levels of polyphosphate in a cellular system comparing cells overexpressing PPK1 and PPK2. If our hypothesis holds true that PPK1 plays an anabolic role, whilst PPK2 plays a catabolic role, then we should expect that a system overexpressing PPK1 should have high polyphosphate levels, whilst a system overexpressing PPK2 should have low polyphosphate levels. It would be difficult for technical reasons to test this actually in MTB, but E. coli will act as an excellent model system for the function of the two enzymes. We will use cells overexpressing either MTB PPK1 or PPK2, and measure cellular polyphosphate levels under a variety of conditions. Stage 2 will provide enzymatic, and stage 3 will provide cellular evidence that support our revised hypothesis for PPK2 function. Besides being scientifically important with regards to our understanding of the roles of polyphosphate within the cell, these enzymes are excellent drug targets for development of new classes of MTB drugs. This will provide a firm foundation for a later submission to the RGC in 2006 to discover inhibitors of PPK2 for drug development against MTB. 1. Kornberg, A., N. N. Rao, et al. (1999). "Inorganic polyphosphate: a molecule of many functions." Annu Rev Biochem 68: 89-125. 2. Kuroda, A., K. Nomura, et al. (2001). "Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E. coli." Science 293(5530): 705-8. 3. Wang, L., C. D. Fraley, et al. (2003). "Inorganic polyphosphate stimulates mammalian TOR, a kinase involved in the proliferation of mammary cancer cells." Proc Natl Acad Sci U S A 100(20): 11249-54. 4. Zhang, H., K. Ishige, et al. (2002). "A polyphosphate kinase (PPK2) widely conserved in bacteria." Proc Natl Acad Sci U S A 99(26): 16678-83.

 

List of Research Outputs

 

Bernini A., Spiga O., Venditti V., Prischi F., Bracci L., Huang J., Tanner J.A. and Niccolai N., Tertiary structure prediction of SARS coronavirus helicase, Biochem Biophys Res Commun. 2006, 343: 1101-1104.

 

Chan C.S.L., Chan D., Cheah K.S.E. and Tanner J.A., Purification and targeting sclerostin: Steps towards, osteoporosis therapy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005.

 

Choi M.Y., Chan D., Cheah K.S.E. and Tanner J.A., Functional studies on sedlin, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, 3 Dec . 2005.

 

Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Mechanistic insight into point mutations in sedlin that result in spondyloepiphyseal dysplasia tarda, FASEB Journal. 2006, 873.9.

 

Ge R., Watt R.M., Sun X., Tanner J.A., He Q., Huang J. and Sun H., Expression and characterization of a histidine-rich protein, Hpn: potential for Ni2+ storage in Helicobacter pylori, Biochemical Journal. 2006, 393: 285-293.

 

Hughes S.J., Tanner J.A., Miller A.D. and Gould I.R., Molecular dynamics simulations of LysRS: an asymmetric state, Proteins. 2006, 62: 649-62.

 

Peng Y., Yang P., Tanner J.A., Huang J., Li M., Lee H.H.F., Xu R.H., Kung H. and Lin M.C., Cold-inducible RNA binding protein is required for the expression of adhesion molecules and embryonic cell movement in Xenopus laevis, Biochem Biophys Res Commun. 2006, 344: 416-424.

 

Tanner J.A., Wright M., Christie E.M., Preuss M.K. and Miller A.D., Investigation into the Interactions between Diadenosine 5',5'''-P1,P4-Tetraphosphate and Two Proteins: Molecular Chaperone GroEL and cAMP Receptor Protein, Biochemistry. 2006, 45: 3096-3106.

 

Tanner J.A., Mechanistic Insight into Point Mutations in Sedlin that Result in Spondyloepiphyseal Dysplasia Tarda., International Proteomics Symposium, May 26th 2006, Hong Kong. 2006.

 

Tanner J.A., WTO TRIPS and its effect on the supply and development of medicines in China, Hong Kong Medical Journal. 2006, 12: 84-86.

 

Zhang X., Chen B., Ng A.H.L., Tanner J.A., Tay D.K.C., So K.F., Rachel R.A., Copeland N.G., Jenkins N.A. and Huang J., Transgenic mice expressing cre-recombinase specifically in retinal rod bipolar neurons, Invest Ophthalmol Vis Sci. 2005, 46: 3515-20.

 

Researcher : Tong HK

List of Research Outputs

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific Community - Stem Cells, Senescence and Cancer. Singapore, Oct 25 - Oct 30, 2005.

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Researcher : Tsang ACC

List of Research Outputs

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific Community - Stem Cells, Senescence and Cancer. Singapore, Oct 25 - Oct 30, 2005.

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Researcher : Tsang KY

List of Research Outputs

 

Chan D., Tsang K.Y., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B., Yamada Y., Bateman J.F., Cheung K.M.C. and Cheah K.S.E., Endoplasmic reticulum stress and reprogramming of hypertrophic chondrocytes, Gordon Research Conference: Collagen. New London, New Hampshire USA, July. 2005.

 

Tsang K.Y., Chan D., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B., Yamada Y., Bateman J.F., Cheung K.M.C. and Cheah K.S.E., Chondroctes Alleviate ER Stress Caused by Unfolded Proteins by Reprogramming, The British Society for Matrix Biology. 25th Anniversary Meeting Pathobiology of Bone and Cartilage. Manchester, UK, 12-13 September . 2005.

 

Tsang K.Y., Molecular pathogenesis of abnormal chondrocyte differentiation in a transgenic mouse model, PhD Thesis. 2006.

 

Researcher : Tsang SL

List of Research Outputs

 

Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Tsang SW

List of Research Outputs

 

Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022.

 

Tsang S.W. and Yao K.M., Involvement of PDZD2 in The Regulation of Pancreatic Beta Cell Development and Function , 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Tsang SW

List of Research Outputs

 

Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022.

 

Tsang S.W. and Yao K.M., Involvement of PDZD2 in The Regulation of Pancreatic Beta Cell Development and Function , 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Tsang WH

List of Research Outputs

 

Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in Sox 10 mouse mutant, Mechanisms of Development. Elsevier, 2005, 122: S177.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in a Sox10 mouse mutant generated by gene targeting , Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the Enteric Neural Crest Development, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Tsang WH

List of Research Outputs

 

Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in Sox 10 mouse mutant, Mechanisms of Development. Elsevier, 2005, 122: S177.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in a Sox10 mouse mutant generated by gene targeting , Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005.

 

Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the Enteric Neural Crest Development, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005.

 

Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Wang J

List of Research Outputs

 

Wang J. and Huang J., Characterization of Intracellular Transportation in KbcU-Mutant Purkinje Cells., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Researcher : Wang Y

Project Title:

The role of posttranslational modifications in regulating the oligomerization and biological functions of adiponectin

Investigator(s):

Wang Y, Xu A

Department:

Genome Research Centre

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

02/2005

Completion Date:

06/2006

 

Abstract:

The main objectives of this project are: 1) To investigate whether posttranslational modifications on each of the four lysine residues are required for the formation of the HMW species of adiponectin in mammalian cells; 2) To examine whether posttranslational modifications can modulate the secretion and/or intracellular assembly of the HMW form of adiponectin; 3) To use an adenovirus-mediated expression system to elucidate the roles of posttranslational modifications in regulating the anti-diabetic actions of adiponectin in vivo.

 

Project Title:

Proteomic and functional characterization of the plasma binding proteins fro the anti-diabetic and anti-inflammatory hormone adiponectin

Investigator(s):

Wang Y

Department:

Genome Research Centre

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:

The Fat-Derived Hormone Adiponectin as a Potential Factor Linking Obesity and Breast Cancer

Investigator(s):

Wang Y, Xu A

Department:

Genome Research Centre

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

06/2006

 

Abstract:

1. Background and Research hypothesis: Obesity and its related diseases are now reaching an epidemic level and form one of the major burdens for our current healthcare system worldwide [1]. Recent epidemiological studies suggested that an increase in the risk of cancer is one of the consequences of obesity. The predominant cancers associated with obesity are lifestyle-related and have a hormonal base including breast, prostate, endometrium, colon and gallbladder cancers etc. [2]. Although the exact mechanism of this relationship remains to be determined, many evidence indicated that excess formation of adipose tissue surrounding the malignant cells might play important roles in tumor-microenvironment interaction and in controlling local cancer growth, invasion and distant metastasis [3]. Adipose tissue was traditionally considered to be an inert energy storage organ. However, recent evidences suggested that adipocytes (fat cells) can also produce a variety of biologically active polypeptides, hormones, growth factors and cytokines, collectively called adipokines [4]. Adipokines elicit their diversified actions on angiogenesis, inflammation, lipid/glucose metabolism, haemostasis, immunity and stress-response etc in an endocrine, paracrine and autocrine manner [5]. It is now generally accepted that endocrine dysfunction of adipose tissue may represent one of the causal links between obesity and systemic insulin resistance/diabetes. Interestingly, diabetes and hyperglycemia are also associated with an elevated risk of developing pancreatic, liver, colon, breast, and endometrial cancer [6], suggesting that the dysregulated secretion of adipokines might represent a general mechanism linking obesity and cancer formation. Indeed, many adipokines, such as leptin, tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6), not only causatively link to metabolic diseases but also play important roles in carcinogenesis. In addition, various growth factors/hormones produced from adipocytes in the local tumor environment might act directly on carcinoma cells to stimulate tumor growth and angiogenesis [7,8]. Breast cancer is the most frequent cancer in women and represents the second leading cause of cancer death among women [9]. Obesity is an independent risk factor for the development of breast cancer and is associated with late-stage disease and poor prognosis [10]. Post-menopausal women with upper body fat predominance have a higher risk of breast cancer [11]. The past several years have provided substantial evidence for the vital roles of stromal cells on the tumorigenesis of the mammary ductal epithelial cells [3]. Stromal cells can influence the level of invasiveness and malignancy of the tumor by producing various matrix metalloproteases (MMPs) and growth/angiogenesis stimulators including IGF, VEGF, HGF, FGF and TGF etc. Notably, adipocyte (fat cell) is one of the predominant stromal cell types in the microenvironment of mammary tissue and the proximity suggests that adipocytes could be a key player in the stromal-ductal epithelium interactions. Indeed, the close relationship between adipocytes and mammary tumor growth has been demonstrated by many in vitro and in vivo pharmacological studies [3]. Aromatase in adipose tissue stroma provides an important source of estrogen for the postmenopausal woman. Mature adipocytes can promote the growth of breast carcinoma cells in a collagen gel matrix culture through cancer-stromal cell interactions [12]. Co-transplantation of tumor cells with adipocytes into mice results in increased tumor growth and metastasis [13]. Leptin, a hormone mainly produced in adipose tissue, could act as a paracrine/endocrine growth factor towards mammary epithelial cells and contribute to the development of breast cancer [14,15]. A recent report by Iyengar P. et al suggested that collagen VI secreted from adipocytes could affect early mammary tumor progression and might represent one of the adipokines that have pro-tumorigenic functions [16]. In summary, these evidences suggest that adipose tissue-derived factors might significantly influence the growth and proliferation of tumorous stroma and malignant cells in the local environment of mammary tissue.Adiponectin is a circulating hormone exclusively secreted from adipocytes. Unlike many other adipokines, such as TNFα, IL-6, leptin, heparin-binding epidermal growth factor-like growth factor, hepatocyte growth factor and resistin etc that are increased in obesity, the circulating levels of adiponectin are inversely correlated with obesity and insulin resistance, two risk factors of breast cancer [10]. Adiponectin has been demonstrated to have insulin-sensitizing, anti-inflammatory, anti-diabetic and anti-atherogenic activities whereas most other adipokines are causatively linked to obesity-related diseases [17]. Replenishment of adiponectin in animal models can reduce the body weight, improve glucose/lipid homeostasis, increase insulin sensitivity, prevent atherosclerosis and ameliorate fatty liver diseases. In addition, adiponectin possesses anti-angiogenic and anti-tumor activities as demonstrated by its ability to inhibit cell growth and migration of vascular endothelial cells, prevent new blood vessel formation, and attenuate the growth of transplanted fibrosarcoma cell tumors in mice [18]. Although the detailed relationship between adiponectin expression in local mammary tissue and the development of breast cancer have not been fully established, recent clinical studies have shown that obese women have reduced serum adiponectin levels and low serum adiponectin levels are significantly associated with an increased risk for breast cancer [10,19-22]. Moreover, tumours in women with the low serum adiponectin levels are more likely to show a biologically aggressive phenotype [22]. Notably, we and others have shown that adiponectin has inhibitory activities on the proliferation of a variety of different types of cells, including aortic smooth muscle cells, myelomonocytic cells, endothelial cells and hepatic stellate cells etc [23-27]. It can selectively bind to various carcinogenic growth factor and prevent the interactions of these growth factors to their respective receptors [24]. In line with these clinical findings, our preliminary studies revealed that recombinant adiponectin could significantly attenuate the cell growth of an estrogen receptor (ER)-negative breast cancer cell line, MDA-MB-231, in a time-dependent manner. It could also inhibit the proliferation stimulated by insulin and several other growth factors in an ER-positive breast cancer cell line, T47D. Moreover, our results from DNA fragmentation assay suggest that apoptosis was significantly induced in MDA-MB-231 cells after 48 hours treatment with adiponectin. Based on aforementioned clinical and experimental evidences, we hypothesize that adiponectin might be a negative regulator in breast cancer development, and that replenishment of this protein might represent a novel therapeutic strategy for the treatment of obesity-related breast cancer. 2. Specific objectives:(1). To test whether adiponectin has inhibitory roles on the migration/invasion of breast carcinoma cells and the angiogenesis stimulated by these cells. (2). To investigate the potential mechanism that underlies the growth-inhibitory effects of adiponectin in breast cancer cells. (3). To evaluate the effects of adiponectin on tumor growth/metastasis in athymic nude mice inoculated with breast cancer cells using adenovirus-mediated overexpression system.

 

List of Research Outputs

 

Poppitt S.D., Leahy F.E., Keogh G.F., Wang Y., Mulvey T.B., Stojkovic M. and Cooper G.J., Effect of high-fat meals and fatty acid saturation on postprandial levels of the hormones ghrelin and leptin in healthy men. , Eur J Clin Nutr. 2006, 60: 77-84.

 

Wang Y., Lam K.S.L., Chan L., Chan K.W., Lam J.B.B., Lam C.W., Hoo R.L.C., Mak W.W., Cooper G.J.S. and Xu A., Posttranslational modifications on the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high-molecular-weight oligomeric complex, J Biol Chem. 2006.

 

Wang Y., Lam K.S.L., Cooper G.J. and Xu A., Structural and functional relationship of Adiponectin as an anti-aging hormone, Frontiers in Biomedical Research. 2005, 62.

 

Xu A., Wang Y., Xu J., Stejskal D., Tam S., Zhang J., Wat N.M.S., Wong W.K. and Lam K.S.L., Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome, Clinical Chemistry. 2006, 52: 405-413.

 

Researcher : Wang Z

List of Research Outputs

 

Wang Z. and Huang J., Mechanism study on two DNA repair systems, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Researcher : Watt RM

Project Title:

New Chemical Proteomics Methods For Selective Protein Capture And Identification

Investigator(s):

Watt RM, Che CM

Department:

Chemistry

Source(s) of Funding:

Small Project Funding

Start Date:

09/2005

 

Abstract:

Chemical proteomics (sometimes referred to as chemistry-based functional proteomics) is an extremely new and exciting area within the chemical biology field. It is broadly defined as being the integration of protein biochemistry and organic chemistry to study protein function on a genome wide scale. The main aims of chemical proteomics are to directly identify, quantify and characterize the ultimate products of genes, i.e. proteins: the bio-molecules that are the main effectors of activity within the cell. This is essential for a true and intimate understanding of cellular biology and function - one that cannot be gleamed solely from genetic or transcription-based analyses.Thus far, most of the research in chemical proteomics has centered on the design and synthesis of small chemical molecules that covalently label target proteins, enabling them to be subsequently identified and/or purified. These chemical probes are designed in such a way as to selectively modify certain classes of proteins, based upon mechanistic similarities (e.g. a shared active-site topography) or due to the nature or arrangement of their component amino acid residues. Aspects of this technology are related to two approaches commonly used in medicinal chemistry, for the identification of possible protein targets of drugs or other bio-molecules within the cell. In the first of these approaches, the drug (or an analogue of it) is linked to a resin or bead, which is used to capture interacting protein species from a cell-free extract. These are subsequently identified by mass spectrometry, protein sequencing or antibody-based methods. In the second approach, a radio- or fluorescently- labeled analogue of the drug or enzyme substrate is used to covalently modify the target protein, which is subsequently purified and identified.Thomas Kodadek (University of Texas Southwest Medical Center), Benjamin Cravatt (Scripps Institute, Skaggs Institute for Chemical Biology) and Matthew Bogyo (Celera Genomics and Stanford University) have conducted some innovative research in this field, developing a number of small chemical affinity probes to target classes of proteins that include proteases, hydrolases and phosphatases. They have outlined two main approaches: a) activity-based probes, and b) affinity-based probes. Activity-based chemical probes may be thought of as being analogous to mechanism-based or suicide inhibitors, in that they irreversibly label proteins directly as a result of their catalytic activities. Affinity-based probes may be thought of as being more general protein labeling agents, not directly linked to protein activity. These reagents do not necessarily target active sites residues, but still bind tightly to specific families of proteins, covalently modifying them. In addition, there are non-specific protein labeling reagents that chemically modify a broad range of proteins, usually targeting specific residues e.g. cysteine thiols or lysine amines.In this proposal, I will take a slightly different approach. I will synthesize a novel set of chemical affinity probes to target families of essential and ubiquitous metabolic and biosynthetic proteins/enzymes. The chemical affinity probes will contain a 'reactive' moiety that will be the main determinant for the types of proteins targeted, as well as a component that will enable subsequent affinity-based protein purification or localization on 2D gels by fluorimetry. Two main types of affinity probes will be synthesized: Highly selective probes targeting functionally-related protein families Less functionally-selective probes, targeting a broader range of proteinsStructurally simple reactive homologues of intermediates in common biosynthetic pathways will be used as components of the probes with a more general selectivity. The rationale behind this being that many of these intermediates are shared between different pathways (which are generally highly conserved between organisms), and they form the structural basis of numerous bioactive compounds. Choosing these types of compound maximizes the likelihood of finding chemical affinity probes of broad applicability. These chemical molecules will be designed to bind irreversibly to families of proteins within cells, in a cell or tissue extract (e.g. mouse liver extract, bacterial cell lysate, etc.) or in a biological fluid sample (e.g. plasma, plant sap, etc.).I will focus on (P450-type) oxidases; intermediates of fatty-acid and polyketide biosynthesis; amino acid and small-molecule biosynthesis and metabolism. Established mechanism-based enzyme inactivators will be used along with other simple drug and biosynthetic compound analogues. Synthetic strategies will be kept deliberately straightforward, maximizing the time spent on optimizing the protein labeling chemistry and experimental conditions, etc. I will consciously use compounds that will be relatively non-specific in nature to maximize the potential for serendipitous discovery.

 

List of Research Outputs

 

Yin W.X., Wu X.S., Li Z.H., Watt R.M., Huang J., Liu D.P. and Liang C.C., Targeted correction of a chromosomal point mutation by modified single-stranded oligonucleotides in a GFP recovery system, Biochemical and Biophysical Research Communications 334 (2005) 1032-1041. 2005.

 

Researcher : Wong CM

List of Research Outputs

 

Leung T.H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in Liver Cancer 2, DLC2, Suppresses Cell Transformation via Inhibition of Rhoa Activity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Wong EYM

List of Research Outputs

 

Wong E.Y.M., Chan Y.S., Wu D.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in mouse hindbrain causes abnormal ear development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September . 2005.

 

Wong E.Y.M., Chan Y.S., Wu D.K. and Cheah K.S.E., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development., Mechanisms of Development . 2005, 122 (Supp 1): S88.

 

Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia . 2005.

 

Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Hoxb3 is involved in the endothelin-1 signaling pathway in patterning the facial branchial arches, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005.

 

Researcher : Wong NS

Project Title:

Kappa-opioid receptor mediated cellular stress response: the role of Inositol 1,4,5-trisphosphate and diacylglycerol

Investigator(s):

Wong NS, Yao KM

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

10/2002

 

Abstract:

The Phospholipase-C (PLC)/inositol-lipid signaling mechanism is itself of widespread importance in cellular regulation and is coupled to all the three major subtypes of opioid receptors (OR), but how this signaling pathway mediates OR-simulated cellular responses is scarcely known. The objective of this project is to investigate the importance of the PLC/inositol-lipid pathway in KappaOr-induced stress responses.

 

Project Title:

Identification of a novel signaling pathway that regulates the transcription of the stress-response gene GADD153

Investigator(s):

Wong NS

Department:

Biochemistry

Source(s) of Funding:

Small Project Funding

Start Date:

11/2003

 

Abstract:

To identity the intracellular signaling pathway that is responsible for mediating the effect of fenretinide/4HPR by elucidating the "4HPR-response element" in the proximal promoter of the GADD153 gene.

 

Project Title:

The establishment of a model cellular system for the investigation of the regulation of mRNA-stability by endoplasmic retriculum stress in pancreactic [beta]-cell

Investigator(s):

Wong NS

Department:

Biochemistry

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

05/2005

 

Abstract:

To establish a cellular model system to investigate how ER-stress produced in pancreatic β-cells may regulate mRNA-stability.

 

Project Title:

The investigation of the interaction between xanthin oxidase on thioredoxin reductase and its pathological implications

Investigator(s):

Wong NS, Lao TTH

Department:

Biochemistry

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

02/2006

 

Abstract:

Thioredoxin reductase (TR) is an NADPH-dependent flavoenzyme that takes part in the metabolic conversion of reactive oxygen species (ROS) to relatively harmless compounds. The biological activity of TR is mainly mediated by its substrate thioredoxin, and together, the two proteins form an important enzyme system that serves to maintain the intracellular environment relatively free from the damage of ROS. The importance of this enzyme system is exemplified by observations that over-expression of these enzymes is able to confer resistance against apoptosis induced by oxidative stress. Furthermore, both TR and thioredoxin have been demonstrated to be essential for normal embryogenesis. It was found recently in preliminary experiments that the enzyme activity of purified TR could be inhibited by xanthine oxidase (XO), an enzyme that is involved in the metabolism of hypoxanthine and xanthine to uric acid, with the production of superoxide. Key issue: The interaction between XO and the thioredoxin reductase system has never been reported. The inhibitory effect of XO on TR would be expected to result in the loss of a cell’s ability to metabolise ROS, which will then accumulate to produce oxidative stress. Our finding may have therefore identified a novel mechanism whereby XO is able to produce oxidative stress independent of its ability to metabolisef purines. This would be an important issue since XO is known to be up-regulated in a number of pathological circumstances, notably diabetes. Problem being addressed: the mechanism by which XO interacts and inhibits TR is presently unknown. The present study therefroe aims to address this problem by examining the molecular mechanism through which XO may produce an inhibitory effect on TR. The implication of the interaction between XO and TR will then be further examined in pregnancy induced diabetes, by investigating if the inhibition of TR by XO could occur in placental tissues obtained from normal and diabetic women.

 

List of Research Outputs

 

Lai W.L. and Wong N.S., Regulation of GADD153 Expression at Post-transcriptional Level by ROS, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Wong N.S. and Poon W.H., The Kappa-opioid receptor specific agonist U50488H induces mitochondrial stress in cultured human cancer cells., The FEBS Journal (formerly European Journal of Biochemistry). 2005, 272, Supplement 1: n5-029p.

 

Researcher : Wong PM

List of Research Outputs

 

Wong P.M., Lu L. and Sham M.H., HOXB3 Mutation Generated By Gene Targeting Leads to Plasmacytoma, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Wong SYY

List of Research Outputs

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006.

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25.

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September . 2005.

 

Researcher : Wynn SL

List of Research Outputs

 

Au Y.K., Wynn S.L., Cheung K.M.C. and Cheah K.S.E., Foxa2 minimal notochord enhancer element mediates Cre expression in the node and notochord, Mechanisms of Development. 2005, 122 (Supp 1): S88.

 

Au Y.K., Wynn S.L., Cheung K.M.C. and Cheah K.S.E., Foxa2 minimal notochord enhancer element mediates Cre expression in the node and notochord, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia. 2005.

 

Researcher : Yao KM

Project Title:

Investigating the functional involvement of PDZD2 in the regulation of pancreatic beta cell gene expression and function

Investigator(s):

Yao KM, Cheah KSE, Thomas M.K.

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2004

 

Abstract:

To investigate cellular model - inducible silencing of PDZD2 expression in INS-1E cells; to define PDZD2 function by pancreatic beta cell-specific gene inactivation in mice.

 

Project Title:

Investigating the functional involvement of PDZD2 in the regulation of pancreatic beta cell gene expression and function

Investigator(s):

Yao KM

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

01/2005

 

Abstract:

N/A

 

Project Title:

Activation of FOXM1 by the Raf/MEK/MAK pathway and regulation of cell cycle progression at the G2/M phase

Investigator(s):

Yao KM

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

09/2005

 

Abstract:

N/A

 

Project Title:

Activation of FOXM1 by the Raf/MEK/MAK pathway and regulation of cell cycle progression at the G2/M phase

Investigator(s):

Yao KM, Lam EWF

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2005

 

Abstract:

To study of the molecular mechanism(s) underlying the enhancement of FOXM1 activity by Raf/MEK/MAPK signaling; to identify the phosphorylation sites within FOXM1 that mediate the MEK1enhancing effect; to investigate the requirement of the MEK1 enhancing effect for FOXM1 function in cultured cells.

 

Project Title:

Test of sPDZD2 as a modulator of potassium channel function in INS-1E cells

Investigator(s):

Yao KM, Li GR

Department:

Biochemistry

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

01/2006

 

Abstract:

Abnormality in pancreatic beta cell function leads to diabetes that affects millions of people worldwide. With a scarcity of human pancreatic donors, the recent success in islet cell transplantation as a treatment procedure has generated intense interest into the identification of factors that can enhance and maintain pancreatic beta cell function for generating renewable beta cell sources for transplantation. PDZD2 is a multi-PDZ (for PSD95, Discs-large and ZO-1) domain factor isolated based on its interaction with E2A proteins that regulate the gene expression and physiological function of diverse cell types including pancreatic beta cells (1). Recent analysis of PDZD2 expression reveals strong expression of the protein in pancreatic insulin-secreting beta cells, but not the glucagon-secreting alpha cells. (2) Using an antiserum raised against the C-terminus of the PDZD2, we demonstrated that full-length PDZD2 is subjected to extensive proteolytic processing to generate its C-terminus as a ~37kDa secreted protein, named sPDZD2 (3). Immunoblot analysis indicated expression of both the full-length and secreted forms of PDZD2 in the beta-like cell line INS-1E (2). INS-1E cells express many of the properties of isolated primary rat islet beta cells, including glucose-stimulated insulin secretion, and represent a ready source of beta-like cells for functional and gene expression analysis. To investigate the extracellular signaling function of sPDZD2, a recombinant sPDZD2 protein was synthesized. In culture media with limiting serum, co-incubation with sPDZD2 stimulated the proliferation of INS-1E cells (2). The mitogenic effect was concentration-dependent, with maximal effects detected at concentrations ranging from 0.001 nM to 0.1 nM. As a mitogen of beta-like cells, sPDZD2 will be useful for the optimization of beta cell growth and differentiation in vitro. Little is known about the molecular mechanism(s) underlying the mitogenic effect of sPDZD2. Interestingly, pancreatic islet cells, isolated from a transgenic mouse line with sPDZD2 over-expressed using the rat insulin II promoter, showed dramatic decreases in insulin secretion upon glucose stimulation (4). In islet beta cells, the glucose-sensitive secretory response is triggered by suppression of the ATP-sensitive potassium (KATP) channels (5). At low plasma glucose concentrations, KATP channels remain open to maintain the hyperpolarized (or background) state. With increases in glucose level and hence the ATP/ADP ratio, KATP channels become inhibited and the resulting membrane depolarization leads to activation of calcium channels and eventually insulin release. Also involved in the regulation of action potential in insulin-secreting cells are the delayed outward rectifier Kv channels, which express at high levels in pancreatic beta cells (6). It would be very interesting to determine whether sPDZD2 exerts its inhibitory effect on glucose-stimulated insulin secretion through modulation of KATP and Kv channel activities. Further, a functional link between cell proliferation and Kv channel activity has been demonstrated recently. It remains to be analyzed whether modulation of Kv channel activity may be a means by which sPDZD2 exercises its concentration-dependent mitogenic effects on INS-1E cells. Two recent communications also indicate a connection between PDZD2/sPDZD2 and ion channel function. Using yeast two-hybrid screens, Dr. Stockand (University of Texas Health Science Center) and Dr. Okuse (Imperial College London) independently identified PDZD2 as the interactor of sodium channels (ENaC and Nav1.8, respectively). For ENaC, co-expression with a GFP-fusion protein containing just the last two PDZ domains as in sPDZD2 was enough to activate channel activity by 8-fold. On the other hand, suppression of PDZD2 expression in cultured sensory neurons by siRNA caused a huge reduction of Nav1.8 current. Taken together, these preliminary findings point towards PDZD2/sPDZD2 playing novel regulatory roles on channel function. We hypothesize that sPDZD2 exerts its effect on the proliferation and secretory function of INS-1E cells via modulation of potassium channel activities. In collaboration with Dr. G. Li (Department of Medicine, HKU), we propose to investigate the effect of recombinant sPDZD2 on the activities of KATP and Kv channels expressed in INS-1E cells. Any detectable effect will be correlated with the mitogenic and secretory responses of the treated cells. The proposed analyses will shed light into the molecular mechanism underlying the biological effects of sPDZD2, which is of major biological interest and relevance to devising better strategies to enhance beta cell growth for islet transplantation. Reference 1. Thomas, M. K.+, Yao, K.-M. +, Tenser, M., Wong, G. G., and J. F. Habener. 1999. Bridge-1: A novel PDZ-domain coactivator of E2A-mediated regulation of insulin gene transcription. Mol. Cell. Biol. 19: 8492-8504. +Equal contribution 2. Ma, R. Y. M., Tam, T. S. M., Suen, A. P., Tsang, S. W., Yeung, P. M.-L., Chung, S. K., Thomas, M. K., Leung, P. S., and K.-M. Yao. 2005. Secreted PDZD2 exerts concentration-dependent effects on the proliferation of pancreatic beta cells. Int. J. Biochem. Cell Biol. In press. 3. Yeung, M.-L., Tam, T. S. M., Tsang, A. C. C., and K.-M. Yao. 2003. Proteolytic cleavage of PDZD2 generates a secreted peptide containing two PDZ domains. EMBO Rep. 4: 412-418. 4. Tsang, S. W., and K.-M. Yao. 2005. Unpublished data. 5. Yokoshiki, H., Sunagawa, M., Seki, T., and Sperelakis, N. 1998. ATP-sensitive K+ channels in pancreatic, cardiac and vascular smooth muscle cells. Am. J. Physiol. 274: C25-C37. 6. Roe, M. W., Worley, J. F. III, Mittal, A. A., Kuznetsov, A., DasGupta, S., Mertz, R. J., Witherspoon, S. M. I., Blair, N., Lancaster M. E., McIntyre, M. S., Shehee, W. R., Dukes, I. D., and L. H. Philipson. 1996. Expression and function of pancreatic beta cell delayed rectifier K+ channels. Role in stimulus-secretion coupling. J. Biol. Chem. 271: 32241-32246.

 

List of Research Outputs

 

Lee J.H., Volinic J.L., Banz C., Yao K.M. and Thomas M.K., Interactions with p300 enhance transcriptional activation by the PDZ-domain coactivator Bridge-1., J. Endocrinol. 2005, 187: 283-292.

 

Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005.

 

Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022.

 

Madureira P.A., Varshochi R., Constantinidou D., Francis R.E., Coombes R.C., Yao K.M. and Lam E.W., The Forkhead box M1 protein regulates the transcription of the estrogen receptor alpha in breast cancer cells., J. Biol. Chem.. 2006, 281: 25167-25176.

 

Tam C.W., Cheng A.S., Lam A.C.W., Yik S.Y., Yao K.M. and Shiu S.Y.W., Prostate Cancer Growth Modulation By sPDZD2, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005, 1.18.

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific Community - Stem Cells, Senescence and Cancer. Singapore, Oct 25 - Oct 30, 2005.

 

Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

 

Tsang S.W. and Yao K.M., Involvement of PDZD2 in The Regulation of Pancreatic Beta Cell Development and Function , 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Researcher : Yau TO

Project Title:

The role of HDPR1, a novel inhibitor of the WNT/β-catenin signalling pathway, in hepatocellular carcinoma

Investigator(s):

Yau TO, Fan ST, Ng IOL

Department:

Centre for the Study of Liver Disease

Source(s) of Funding:

Small Project Funding

Start Date:

11/2004

Completion Date:

10/2005

 

Abstract:

To study the expression of HDPR1 at mRNA levels in human HCCs and HCC cell lines; to investigate the common mechanisms, such as promoter hypermethylation and loss of heterozygosity, by which the expression of HDPR1 in HCC is downregulated; to study the function of HDPR1 in HCC cell lines.

 

List of Research Outputs

 

Researcher : Yeung ML

List of Research Outputs

 

Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005.

 

Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022.

 

Researcher : Yeung ML

List of Research Outputs

 

Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005.

 

Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022.

 

Researcher : Yeung MN

List of Research Outputs

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Expression of heparanase in newborn mouse growth plates, Glycoconjugate Journal, GlycoXVIII, XVIII International Symposium on Glycoconjugates, Firenze, Italy. 2005.

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan Sulfates and Heparanase in the Mineralizing Matrix of Developing Mouse Growth Plate., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan sulfates and heparanase at the mineralization front of the developing growth plate., Proteoglycans in Signaling, Stockholm (Runo), Sweden, September 7-11,2005.

 

Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57.

 

Researcher : Yip MS

List of Research Outputs

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006.

 

Researcher : Zhang JCL

Project Title:

Functional analysis of SM22[beta] by tissue-specific targeted deletion in mice

Investigator(s):

Zhang JCL, Cheah KSE, Lau CP, Feil R., Parmacek M.S.

Department:

Medicine

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

09/2003

Completion Date:

09/2005

 

Abstract:

N/A

 

Project Title:

Cardiovascular analysis of a novel murine model of cardiomyopathy and sudden death

Investigator(s):

Zhang JCL

Department:

Medicine

Source(s) of Funding:

Incentive Award for RGC CERG Fundable But Not Funded Projects

Start Date:

07/2004

Completion Date:

09/2005

 

Abstract:

N/A

 

List of Research Outputs

 

Cheah K.S.E. and Zhang J.C.L., Procollagen IIA deficient mice. , US Patent application no. PTC/CN2005/001114. pending . 2005.

 

Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25.

 

Researcher : Zhang X

List of Research Outputs

 

Zhang X., Chen B., Ng A.H.L., Tanner J.A., Tay D.K.C., So K.F., Rachel R.A., Copeland N.G., Jenkins N.A. and Huang J., Transgenic mice expressing cre-recombinase specifically in retinal rod bipolar neurons, Invest Ophthalmol Vis Sci. 2005, 46: 3515-20.

 

Researcher : Zhang Y

List of Research Outputs

 

Zhang Y. and Shum D.K.Y., Functional Study of Heparanase in the explant cultures of rat dorsal root ganglia., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57.

 

Researcher : Zhou Z

Project Title:

Investigation of alternations in growth factor signaling and their contribution to defective intramembranous bone formation in mice lacking MT1-MMP

Investigator(s):

Zhou Z

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2003

 

Abstract:

To understand the Nature of defective calvarial osteogenesis and alterations in FGF signaling in MT1-MMP homozygous mutant mice; to regulate the MT1-MMP by FGF signaling.

 

Project Title:

Investigation of alternations in growth factor signaling and their contribution to defective intramembranous bone formation in mice lacking MT1-MMP

Investigator(s):

Zhou Z

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

09/2003

 

Abstract:

N/A

 

Project Title:

Investigating the mechanism underlying anti-cancer effect of farnesyl transferase inhibitors

Investigator(s):

Zhou Z

Department:

Biochemistry

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

01/2005

Completion Date:

12/2005

 

Abstract:

In this study, we will assess whether FT inhibitors cause growth arrest in tumor cells by compromise the DNA repair machinery. We will also make two constructs that express mutant prelamin A or lamin A to assess whether expressing truncated or unprocessed lamin A in tumor cells will cause increased genomic instability and enhanced sensitivity to chemotherapy. This study will help to understand the profound effects of FT inhibitors on tumor cells and help to develop effective chemotherapy in cancer patients.

 

Project Title:

Genomic instability and premature aging in mice lacking Zmpste24

Investigator(s):

Zhou Z

Department:

Biochemistry

Source(s) of Funding:

Merit Award for RGC CERG Funded Projects

Start Date:

08/2005

 

Abstract:

N/A

 

Project Title:

Genomic instability and premature aging in mice lacking Zmpste24

Investigator(s):

Zhou Z, Cheah KSE

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

08/2005

 

Abstract:

To examine genomic stability in Zmpste24-I- mice and in human fibroblasts derived from HGPS patients; to assess whether unprocessed prelamin A is a causing factor for unstable genome and premature aging; to assess the impact of Zmpste24 deficiency and mutated lamin A on DNA repair; to assess whether loss of Zmpste24 and mutated lamin A results in mis-localized and decreased pRB protein.

 

Project Title:

Understanding the regulation of MT1-MMP activity in tumorigenesis

Investigator(s):

Zhou Z

Department:

Biochemistry

Source(s) of Funding:

Matching Fund for NSFC Young Researcher Award

Start Date:

05/2006

 

Abstract:

To investigate the effect of mis-regulated MT1-MMP activity on development and tumorigenesis; to understand how the mis-regulated MT1-MMP activity regulate FGF signaling which contributes to the defective development and disturbed angiogenesis.

 

List of Research Outputs

 

Björndahl M., Cao R., Nissen J., Clasper S., Xie Y., Zhou Z., Jackson D., Jon Hansen A. and Cao Y., Insulin-like Growth Factor-1and -2 Induce Lymphangiogenesis , Proc Natl Acad Sci Usa. 2005, 102(43): 15593-8.

 

Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785.

 

Religa P., Cao R., Bjorndahl M., Zhou Z., Zhu Z. and Cao Y., Presence Of Bone Marrow-derived Circulating Progenitor Endothelial Cells In The Newly Formed Lymphatic Vessels, Blood. 2005, 106(13): 4184-90.

 

Wang J., Hoshijima M., Lam J., Zhou Z., Jokiel A., Dalton N.D., Hultenby K., Ruiz-Lozano P., Ross J., Tryggvason K. and Chien K.R., Cardiomyopathy Associated With Microcirculation Dysfunction In Laminin Alpha4 Chain-deficient Mice, J Biol Chem. 2006, 281(1): 213-20.

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Expression of heparanase in newborn mouse growth plates, Glycoconjugate Journal, GlycoXVIII, XVIII International Symposium on Glycoconjugates, Firenze, Italy. 2005.

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan Sulfates and Heparanase in the Mineralizing Matrix of Developing Mouse Growth Plate., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

 

Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan sulfates and heparanase at the mineralization front of the developing growth plate., Proteoglycans in Signaling, Stockholm (Runo), Sweden, September 7-11,2005.

 

Zhou Z., Distinguished Oversea Young Scientist Award, National Natural Science Foundation of China. 2006.

 

Zhou Z., Genomic Instability in Laminopathies the difference between Cardiomyopathy and muscular dystrophy, Harvard University. 2005.

 

Zhou Z., Genomic Instability in Laminopathy-based Premature Aging, Annual Meeting of American Society of Cell Biology. 2005.

 

Zhou Z., How To Get Old Fast? , Karolinska Institute, SWEDEN. 2005.



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