DEPT OF BIOCHEMISTRY
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Researcher
: Au SWN |
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List of Research Outputs |
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Huang Y., Choi M.Y., Au S.W.N., Au D.M., Lam V.M.S. and Engel P.C., Purification and detailed study of two clinically different human glucose 6-phosphate dehydrogenase variants, G6PD(Plymouth) and G6PD (Mahidol): Evidence for defective protein folding as the basis of disease., Mol Genet Metab. 2008. 2008, 93(1): 44-53. |
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List of Research Outputs |
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Cheah
K.S.E., Szeto Y.Y., Au Y.K., Wynn S., Geng G., Chan Y.S., Chan W.Y., Cheung K.M.C. and Fritzsch B., Context
dependent impact of the Y440X campomelic dysplasia Sox9 mutation, ACGA-HKSMG
International Conference on Genetic and Genomic Medicine, |
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Cheah
K.S.E., Szeto Y.Y., Au Y.K., Chan Y.S., Lovell-Badge R. and Fritzsch
B., Hearing and balance defects in a mouse model of campomelic dysplasia, Gordon
Research Conference on Craniofacial Morphogenesis and Tissue Regeneration. |
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Szeto
Y.Y., Au Y.K., Wynn S., Chan Y.S., Lovell-Badge R., Chan W.Y.,
Fritzsch B. and Cheah K.S.E., A mouse
model for hearing and balance defects in campomelic dysplasia, 6th
Molecular Biology of Hearing & Deafness Conference. |
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Researcher
: Cai K |
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List of Research Outputs |
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Cai K., Tse L.Y., Leung C., Tam P.K.H., Xu R. and Sham M.H., Suppression of lung tumor growth and metastasis in mice by adeno-associated virus-mediated expression of vasostatin, Clinical Cancer Research. 2008, 14(3): 939-949. |
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Researcher
: Chan C |
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List of Research Outputs |
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Chan C., Liu H., Chan Y.S. and Shum D.K.Y., 4-O-sulfated Chondroitins Contribute to Axon-restrictive Property in Schwann cell-as-trocyte Encounters, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
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Chan C., Axon-restrictive Chondroitin Sulfates at the Schwann Cell-astrocyte Interface, MPhil. 2007. |
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Chan C., Leung M.C.M., Chan D., Cheah K.S.E. and Tanner J.A., Identification of Sclerostin Interacting Partners: Steps Towards Osteoporosis Therapy with Aptamer-based Inhibitors, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Correlating Protein Structure with Disease - Understanding the Mechanism of SEDT, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Researcher
: Chan CH |
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List of Research Outputs |
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Chan C.H., Shum D.K.Y., Tipoe G.L., Mak J.C.W., Leung T.M. and Ip M.S.M., Upregulation of ICAM-1 expression in bronchial epithelial cells by airway secretions in bronchiectasis, Respiratory Medicine. 2008, 102: 287-298. |
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Leung O.Y.V., Chan C.H., Ip M.S.M. and Shum D.K.Y., Development of heparin and heparan sulfate from recombinant syndecan-1 as a potential therapeutic for bronchiectasis, Third International Symposium on Healthy Aging: “Improving the Health of an Aging Population” March 1-2, 2008. |
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Researcher
: Chan CP |
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List of Research Outputs |
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Chan C.P., Chin K.T. and Jin D., N-linked Glycosylation Is Required for Proteolytic Activation of Liver-enrich Transcription Factor CREB-H , 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Mak
T.Y., Chan C.P. and Jin D., Regulation of CREB |
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Researcher
: Chan CP |
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List of Research Outputs |
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Chan C.P., Chin K.T. and Jin D., N-linked Glycosylation Is Required for Proteolytic Activation of Liver-enrich Transcription Factor CREB-H , 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Mak
T.Y., Chan C.P. and Jin D., Regulation of CREB |
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Researcher
: Chan CSL |
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List of Research Outputs |
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Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Periostin interacts with sclerostin and inhibits its antagonistic effect on Wnt signalling, International Bone and Mineral Society (IBMS) Workshop: Bone biology and therapeutics, Davos, Switzerland. 2008. |
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Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Purification and identification of sclerostin interacting partners: steps towards therapy with aptamer-based inhibitors, HKU 12th Research Postgraduate Symposium. 2007. |
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Lee B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tung L.F., Song Y. and Tanner J.A., Understanding How Polymorphisms in Cerberus-like Result in low Bone Mineral Density, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Researcher
: Chan D |
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Project Title: |
A matrix metalloproteinase detector for in vitro monitoring of enzyme activity |
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Investigator(s): |
Chan D, Lam E |
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Department: |
Biochemistry |
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Source(s) of Funding: |
Research Initiation Programme |
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Start Date: |
06/2002 |
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Abstract: |
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To establish efficient in vitro reporter assays for aggrecanase and other MMPs. |
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Project Title: |
The role of matrix remodeling in endochondral bone formation |
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Investigator(s): |
Chan D, Cheah KSE |
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Department: |
Biochemistry |
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Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
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Start Date: |
10/2002 |
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Abstract: |
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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. |
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Project Title: |
The biology of digit formation and its pathology in brachydactyly |
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Investigator(s): |
Chan D |
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Department: |
Biochemistry |
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Source(s) of Funding: |
Germany/Hong Kong Joint Research Scheme |
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Start Date: |
01/2005 |
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Abstract: |
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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. |
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Project Title: |
Genomic analysis of the regulation of osteoblast activity in a mouse with generalized hyperostosis |
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Investigator(s): |
Chan D, Cheah KSE, Cheung KMC |
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Department: |
Biochemistry |
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Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
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Start Date: |
01/2005 |
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Abstract: |
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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. |
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List of Research Outputs |
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Abbah S.A., Lu W.W., Chan D., Cheung K.M.C., Zhao F., Li Z., Leong J.C.Y. and Luk K.D.K., Osteogenic behavior of alginate encapsulated bone marrow stromal cells: an in vitro study, J Mater Sci Mater Med. 2008, 19(5): 2113-9. |
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Aladin Kaderbatcha D.M., Lu W.W., Cheung K.M.C., Ngan A.H.W., Chan D. and Luk K.D.K., Association of Trp2 allele with changes in morphology and nano mechanics of the human intervertebral disc collagens, Best Basic Science Paper Award for Associate Member, 27th Annual Congress of the Hong Kong Orthopaedic Association, Hong Kong, November 17-18, 2007. 2007. |
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Aladin
Kaderbatcha D.M., Lu W.W., Cheung K.M.C., Ngan A.H.K., Chan D. and Luk K.D.K., Correlation between the
Compressive Macro-mechanical Properties of the Human Nucleus Pulposus and the
Nano Structure of its Individual Collagen Fibrils, World Forum for Spine
Research - The Intervertebral Disc. |
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Aladin
Kaderbatcha D.M., Cheung K.M.C., Chan D., Yee A.F.Y., Jim J.J.T., Luk K.D.K. and Lu W.W., Expression of the Trp2 allele
of COL |
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Chan
B.P., Hui T.Y., Chan G.C.F., Chan D. and Cheung K.M.C., Collagen-mesenchymal stem
cell microspheres for regenerative medicine., World Forum for Spine
Research, Kyoto, Japan (Best oral pesentation award), Jan 23-26. |
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Chan B.P., Hui T.Y., Chan G.C.F., Chan D. and Cheung K.M.C., Collagen-mesenchymal stem cell microspheres for regenerative medicine, Best Oral Presentation Award, World Forum for Spine Research - the intervertebral disc, first Japanese meeting, Kyoto, Japan, January 23-26, 2008. 2008. |
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Chan C., Leung M.C.M., Chan D., Cheah K.S.E. and Tanner J.A., Identification of Sclerostin Interacting Partners: Steps Towards Osteoporosis Therapy with Aptamer-based Inhibitors, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Chan C.C.Y., Chan D., Luk K.D.K. and Cheah K.S.E., Understanding the Function of Sedl gene and the Molecular Pathogenesis of spondyloepiphyseal Dysplasia Tarda., 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia. October 28 – November 1, 2007. |
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Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Periostin interacts with sclerostin and inhibits its antagonistic effect on Wnt signalling, International Bone and Mineral Society (IBMS) Workshop: Bone biology and therapeutics, Davos, Switzerland. 2008. |
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Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Purification and identification of sclerostin interacting partners: steps towards therapy with aptamer-based inhibitors, HKU 12th Research Postgraduate Symposium. 2007. |
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Chan
C.W., Gantenbein B., Leong V.Y.L.,
Chan D., Lu W.W., Luk K.D.K., Cheung K.M.C. and Ito K., Cell
Repopulation of the Frozen Intervertebral Disc by Bone Marrow-derived Stromal
Cells., World Forum for Spine Research - The Intervertebral Disc. |
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Chan D., Genetic Risk Factors for Intervertebral Disc Degeneration, World Forum for Spine Research - the intervertebral disc, first Japanese meeting, Kyoto, Japan, January 23-26, 2008 . 2008. |
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Chan
D., Genetic risk factors for intervertebral
disc degeneration, Gordon Research Conference: Collagen. |
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Chan W.C.W., Ng V.C.W., Cheah K.S.E. and Chan D., Molecular Basis For Growth Plate Abnormalities In A Mouse Model With Schmid Metaphyseal Chondrodyplasia, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia, 28 October - 1 November 2007. |
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Chan W.C.W., Ng V.C.W., Cheah K.S.E. and Chan D., Molecular Basis For Growth Plate Abnormalities In A Mouse Model With Schmid Metaphyseal Chondrodyplasia, Best Poster Award, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia. 2007. |
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Chan W.L., Chan D., Lee S., Cheah K.S.E. and Tanner J.A., The Proteomics of Protein Misfolding in Chondrocytes, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Chan
Y.L., Wu S.L., Liu X.M., |
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Cheah
K.S.E., Leong V.Y.L., Gao B., Dung W.F., Leung K.K.H., Wynn S.L., Lau J.Y.B., Niewiadomska A.K., Melhado I.G. and Chan D., Dual roles of Sox |
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Cheng
H.W., Tsui K., Cheung K.M.C., Chan D. and Chan B.P., Decellularization of
chondrocyte-encapsulated collagen microspheres, World Forum for Spine
Research the Intervertebral Disc. |
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Cheung
K.M.C., Karppinen J., Chan D.,
Fan B., Ho D.W.H., Kao P.Y.P., Song Y., Sham P.C., Cheah K.S.E., Leong J.C.Y. and Luk K.D.K., Age-related changes versus
degenerative disc disease. World Forum for Spine Research, World Forum for
Spine Research - The Intervertebral Disc. |
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Cheung K.M.C., Song Y., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S.P., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Association of the asporin D14 allele with lumbar disc degeneration, Spineweek 2008, Geneva, Switzerland, May 26-31, 2008. |
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Cheung
M.C.H. and Chan D., Book
And Media Reviews title: Principles Of Developmental Genetics, In: John L.
Zeller, MD, PhD Contributing Editor Section Editor: Book and Media Reviews
Journal of the American Medical Association (JAMA) , The Journal Of The
American Medical Association. |
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Chik H.H.Y., Chan W.C.W., Cheng Y.W., Tsang K.Y., Cheah K.S.E. and Chan D., Ectopic Expression Of Unfolded Mutant Collagen X In Bone Cells Results In Generalised Hyperostosis in Mice, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Ressort, Cairns, Australia. 2007. |
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Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Correlating Protein Structure with Disease - Understanding the Mechanism of SEDT, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Guo C.X., Irwin M.G., Cheung K.M.C. and Chan D., An effective dose of Valdecoxib in experimental mouse models of pain, Methods Find Exp Clin Pharmacol. 2007, 29(6): 383-388. |
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Ho D.W.H., Chan D., Cheung K.M.C., Sham P.C. and Song Y., Family-base linkage and case control association studies, Current Orthopaedics. 2008, 22: 245-250. |
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Ho D.W.H., Cheung K.M.C., Chan D., Cheah K.S.E., Karppinen J., Sham P.C. and Song Y., LINKAGE ANALYSIS WITH SUBSEQUENT FINE-MAPPING ON FAMILIAL EARLY ONSET-DEGENERATIVE DISC DISEASE, SpineWeek 2008, Geneva, SWITZERLAND. 2008. |
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Ho D.W.H., Cheung K.M.C., Chan D., Karppinene 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, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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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. World Forum for Spine Research., The
Intervertebral Disc. |
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Ho D.W.H., Cheung K.M.C., Chan D., Cheah K.S.E., Karppinen J., Sham P.C. and Song Y., Linkage analysis with subsequent fine-mapping on familial early onset-degenerative disc disease., Spine Week 2008, Geneva, May 26-31, 2008. |
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Ho G., Leung Y.L., Chan D. and Cheung K.M.C., Effect of severity of intervertebral disc injury on mesenchymal stem cell-based regeneration, Connective Tissue Research. 2008, 49: 15-21. |
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Hui T.Y., Cheung K.M.C., Cheung W.L., Chan D. and Chan B.P., In vitro chondrogenic differentiation of human mesenchymal stem cells in collagen microspheres: influence of cell seeding density and collagen concentration, Biomaterials. Elsevier Ltd., 2008, 29: 3201-3212. |
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Kao P.Y.P., Chan D., Cheah K.S.E., Cheung K.M.C., Karppinene J., Yip S.P., Sham P.C. and Song Y., Genome-wide Association Study of Degenerative Disc Disease (DDD) , 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Kao P.Y.P., Chan D., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Cheah K.S.E., Song Y. and Sham P.C., Genome-wide association study of degenerative disc disease (DDD)., Spine Week 2008, Geneva, May 26-31, 2008. . 2008. |
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Kao
P.Y.P., Chan D., Cheah K.S.E., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Song Y. and Sham P.C., Genome-wide association study
of degenerative disc disease (DDD)., World Forum for Spine Research - The
Intervertebral Disc. |
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Kao P.Y.P., Chan D., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Cheah K.S.E., Song Y., Sham P.C. and Sham P.C., Genome-wide association study of degenerative disc disease, Spineweek 2008, Geneva, Switzerland, May 26-31, 2008. |
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Lam
K.O., Yeung K.W.K., Chan Y.L., Wu S.L., Liu X.M., Chung
C.Y., |
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Lee B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tung L.F., Song Y. and Tanner J.A., Understanding How Polymorphisms in Cerberus-like Result in low Bone Mineral Density, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Leung Y.L., Hung S.C., Li L.C., Wu E.X., Luk K.D.K., Chan D. and Cheung K.M.C., Age-related degeneration of lumbar intervertebral disc in rabbit reveal by deuterium oxide-assisted MRI, Best Poster Award, World Forum for Spine Research - the intervertebral disc, first Japanese meeting, Kyoto, Japan, January 23-26, 2008 . 2008. |
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Leung Y.L., Hung S.C., Chan Li L.C., Wu E.X., Luk K.D.K., Chan D. and Cheung K.M.C., Age-related degeneration of lumbar intervertebral discs in rabbits revealed by deuterium oxide-assisted MRI, World Forum for Spine Research - the Intervertebral Disc. 2008. |
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Leung Y.L., Hung S.C., Chan Li L.C., Wu E.X., Luk K.D.K., Chan D. and Cheung K.M.C., Aged-related degeneration of lumbar intervertebral discs in rabbits revealed by deuterium oxide-assisted MRI, World Forum for Spine Research - The Interveretegral Disc, First Japanese Meeting, Kyoto, Japan, January 23-26, 2008. |
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Leung Y.L., Wu E.X., Luk K.D.K., Chan D. and Cheung K.M.C., Cell quantity and degenerative stage dependent effect of allogeneic mesenchymal stem cells on regeneration of intervertebral disc, 14th International Meeting on Advanced Spine Techniques. 2007. |
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Li J., Wu Y., Wu E.X., Chan D., Cheah K.S.E. and Zhou Z., Accelerated Senescence in Degenerate Intervertebral Disc of Laminopathy-based Premature Aging Mouse Model, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Luk K.D.K., Leung Y.L., Hung S.C., Tsui Y.K., Lee M.K., Chan Li L.C., Lo G.G., Masuda K., Wu E.X. and Chan D., Allogeneic mesenchymal stem cell transplantation into the intervertebral disc; effect of severity of degeneration and cell number on regeneration, 15th Triennial Congress of Asia Pacific Orthopaedic Association, Seoul, Korea, September 9-13, 2007. |
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Song Y., Ho D.W.H., Karppinen J., Kao P.Y.P., Fan B.J., Luk K.D.K., Yip S.P., Leong J.C.Y., Cheah K.S.E., Sham P.C., Chan D. and Cheung K.M.C., Association between promoter-1607 polymorphism of MMP1 and lumbar disc disease in Southern Chinese, BMC Medical Genetics. 2008, 9(1): 38. |
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Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S.P., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Association of the asporin D14 allele with lumbar disc degeneration in Asians, American Journal of Human Genetics. 2008, 82(3): 744-747. |
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Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Genetic Risk Factors For Intervertebral Disc Degeneration, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia, 28 October - 1 November 2007. |
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Song Y., Sham P.C., Cheung K.M.C. and Chan D., Genetics of disc degeneration, Current Orthopaedics. 2008, 22: 259-266. |
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Song
Y., Chan D., Kao P.Y.P., Ho D.W.H., Fan B., Karpinen J., Yip S.Y., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Cheung K.M.C., Three genes in the
aggrecan degradation pathway act synergistically to predispose to
degenerative disc disease., World Forum for Spine Research - The
Intervertebral Disc. |
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Tam W.K., Cheung K.M.C., Chan D., Leong V.Y.L., Luk K.D.K. and Zhou G.Q., Both HIF-1aand HIF-2aare Present in
Prenatal and Postnatal Nucleus., World Forum for Spine Research - The
Intervertebral Disc. |
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Trebicz-Geffen M., Robinson D., Evron Z., Glaser T., Fridkin M., Kollander Y., Vlodavsky I., Ilan N., Law K.F., Cheah K.S.E., Chan D., Werner H. and Nevo Z., The molecular and cellular basis of exostosis formation in hereditary multiple exostoses. , Int J Exp Pathol. . 2008, Epub. |
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Tsui
Y.K., Leung Y.L., Kao R.Y.T., Chan D., Masuda K. and Cheung K.M.C., High throughput screening
of chemical compounds for the treatment of osteoarthritis, Best Poster
Award, 12th Ressearch Postgraduate Symposium, The |
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Tsui
Y.K., Leung Y.L., Kao R.Y.T., Chan D., Masuda K. and Cheung K.M.C., Identification of
Chemical Compounds for the Treatment of Intervertebral Disc Degeneration with
the Application of High-throughput Screening, World Forum for Spine
Research - The Intervertebral Disc. |
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Yang
F., Chan D., Leung Y.L., Lu W.W., Luk K.D.K. and Cheung K.M.C., Dynamic Changes of Type
II Collagen in the Degenerated Murine Discs., World Forum for Spine
Research - The Intervertebral Disc. |
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Yee
A.F.Y., Melhado I.G., Cheah K.S.E., Cheung K.M.C. and Chan D., Protein expression of the
intervertebral disc: in Health and disease., World Forum for Spine
Research - The Intervertebral Disc. |
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Yee A.F.Y., Melhado I.G., Cheah K.S.E., Chan D. and Cheung K.M.C., Use of tandem mass spectrometry as a tool for proteomics studies in aging and degeneration processes of the intervertebral disc., Spine Week 2008, Geneva, May 26-31, 2008.. 2008. |
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Yee
A.F.Y., Melhado I.G., Cheah K.S.E., Chan D. and Cheung K.M.C., Use of tandem mass
spectrometry as a tool for proteomics studies in aging and degeneration
processes of the intervertebral disc, Spineweek 2008, |
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Yeung
K.W.K., Chan Y.L., Lama K.O., Wu
S.L., Liu X.M., Chung C.Y., |
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Yeung
K.W.K., Chan Y.L., Lam K.O., Liu X.M., Wu S.L., Liu X.Y.,
Chung C.Y., Lu W.W., Chan D., Luk K.D.K., |
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Yeung
K.W.K., Poon R.W.Y., |
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Zhou X.Z., Leung Y.L., Dong Q.R., Cheung K.M.C., Chan D. and Lu W.W., Mesenchymal stem cell-based repair of articular cartilage with polyglycolic acid-hydroxyapatite biphasic scaffold, Int J Artif Organs. 2008, 6: 480-9. |
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Zhu G., Chan D., Cheah K.S.E. and Huang J., KIF5b is Essential for Growth Plate Organization and Cytokinesis, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Researcher
: Chan JKM |
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List of Research Outputs |
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Jin G., Chan J.K.M. and Zhou Z., Genetic approach to Study the Role of MT1-MMP in Tumor Development in Vivo, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Researcher
: Chan SY |
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List of Research Outputs |
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Cheung C.L., Tang L.F., Sham P.C., McClug P., Chan S.Y., Smith D.K., Su A.I., Cheah K.S.E., Kung A.W.C. and Song Y., Genome-wide Haplotype Association Mapping (HAM) in Mice Leads to an Identification of a Genetic Variant in CER1 Associated with Bone Mineral Density in Premenopausal Women, ASBMR 29th Annual Meeting, Honolulu, Hawaii, USA, September 16-19, 2007. |
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Researcher
: Chan WCW |
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List of Research Outputs |
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Chan W.C.W., Zhang J.C.L., Dung W.F., Wong Q., Parmacek M.S., Lau C.P. and Cheah K.S.E., Functional analysis of SM22β by targeted gene deletion in mice. , ACGA-HKSMG International Conference on Genetic and Genomic Medicine, Hong Kong. June 8-11, 2008. . 2008. |
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Chan
W.C.W., Zhang
J.C.L., Dung W.F., Wong Q.,
Parmacek M.S., Lau C.P. and Cheah K.S.E., Functional analysis of
SM22β by targeted gene deletion in mice., ACGA-HKSMG International
Conference on Genetic and Genomic Medicine, |
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Chan W.C.W., Ng V.C.W., Cheah K.S.E. and Chan D., Molecular Basis For Growth Plate Abnormalities In A Mouse Model With Schmid Metaphyseal Chondrodyplasia, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia, 28 October - 1 November 2007. |
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Chan W.C.W., Ng V.C.W., Cheah K.S.E. and Chan D., Molecular Basis For Growth Plate Abnormalities In A Mouse Model With Schmid Metaphyseal Chondrodyplasia, Best Poster Award, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia. 2007. |
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Chik H.H.Y., Chan W.C.W., Cheng Y.W., Tsang K.Y., Cheah K.S.E. and Chan D., Ectopic Expression Of Unfolded Mutant Collagen X In Bone Cells Results In Generalised Hyperostosis in Mice, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Ressort, Cairns, Australia. 2007. |
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Researcher
: Chan WL |
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List of Research Outputs |
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Chan W.L., Chan D., Lee S., Cheah K.S.E. and Tanner J.A., The Proteomics of Protein Misfolding in Chondrocytes, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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List of Research Outputs |
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Wong
E.Y.M., Sae-Pang J.J., Mak S.S.,
Ling K.W., Chan W.Y., Chung S.K.,
Cheah K.S.E. and Sham M.H., Gain-of-function Hoxb3
mutation affects endothelin-1 pathway in craniofacial development., Gordon
Research Conference on Craniofacial Morphogenesis & Tissue Regeneration, |
|
Researcher
: Chau CH |
|
List of Research Outputs |
|
Shum D.K.Y., Chan C., Liu H.Y., Chau C.H. and Chan Y.S., Addressing the pericellular matrix of reactive astrocytes. , Abstracts of Croucher Advanced Study Institute: Innovative Therapies of Movement Disorders, D12. HK. Nov. 27-30. 2007. |
|
Zhang
Y., Chau C.H., Lai C.H., Chan Y.S. and Shum D.K.Y., Heparanase upregulation in
astrocytes and macrophages recruited to the injured spinal cord. Neuroscience
Research 58: S145, 30th Annual Meeting of |
|
Researcher
: Chau PPY |
|
List of Research Outputs |
|
Chau P.P.Y., Mechanism of Genomic Instability in Prelamin A based Premature Ageing, M.Phil thesis. 2007. |
|
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 Sox |
|
Investigator(s): |
Cheah KSE |
|
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 Sox |
|
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: |
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 |
|
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: |
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 |
|
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: |
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, 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, Huang J, Sham MH, Smith DK, 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 Sox |
|
Project Title: |
Functional and genetic analyses of integrin signaling in the early development of the axial skeleton |
|
Investigator(s): |
Cheah KSE, Chan D |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Germany/Hong Kong Joint Research Scheme |
|
Start Date: |
01/2007 |
|
Abstract: |
|
1. To generate conditional loss of function B1 integrin in the node and notochord 2. To generate conditional loss of function of ILK in the node and notochord 3. To analyze the phenotypic and molecular impact of these mutations on development of the embrhonic midline and axial skeleton |
|
List of Research Outputs |
|
Chan C., Leung M.C.M., Chan D., Cheah K.S.E. and Tanner J.A., Identification of Sclerostin Interacting Partners: Steps Towards Osteoporosis Therapy with Aptamer-based Inhibitors, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Chan C.C.Y., Chan D., Luk K.D.K. and Cheah K.S.E., Understanding the Function of Sedl gene and the Molecular Pathogenesis of spondyloepiphyseal Dysplasia Tarda., 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia. October 28 – November 1, 2007. |
|
Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Periostin interacts with sclerostin and inhibits its antagonistic effect on Wnt signalling, International Bone and Mineral Society (IBMS) Workshop: Bone biology and therapeutics, Davos, Switzerland. 2008. |
|
Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Purification and identification of sclerostin interacting partners: steps towards therapy with aptamer-based inhibitors, HKU 12th Research Postgraduate Symposium. 2007. |
|
Chan W.C.W., Zhang J.C.L., Dung W.F., Wong Q., Parmacek M.S., Lau C.P. and Cheah K.S.E., Functional analysis of SM22β by targeted gene deletion in mice. , ACGA-HKSMG International Conference on Genetic and Genomic Medicine, Hong Kong. June 8-11, 2008. . 2008. |
|
Chan
W.C.W., Zhang J.C.L., Dung W.F., Wong Q., Parmacek M.S., Lau C.P. and Cheah K.S.E., Functional analysis of
SM22β by targeted gene deletion in mice., ACGA-HKSMG International
Conference on Genetic and Genomic Medicine, |
|
Chan W.C.W., Ng V.C.W., Cheah K.S.E. and Chan D., Molecular Basis For Growth Plate Abnormalities In A Mouse Model With Schmid Metaphyseal Chondrodyplasia, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia, 28 October - 1 November 2007. |
|
Chan W.C.W., Ng V.C.W., Cheah K.S.E. and Chan D., Molecular Basis For Growth Plate Abnormalities In A Mouse Model With Schmid Metaphyseal Chondrodyplasia, Best Poster Award, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia. 2007. |
|
Chan W.L., Chan D., Lee S., Cheah K.S.E. and Tanner J.A., The Proteomics of Protein Misfolding in Chondrocytes, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Cheah K.S.E., Insights into the function of Sox9 and the molecular pathogenesis of campomelic dysplasia. , The 9th AEARU (The Association of East Asian Research Universities) Workshop on Molecular Biology and Biotechnology, HKUST, Hong Kong, 25-26 March 2008. . 2008. |
|
Cheah
K.S.E., Szeto
Y.Y., Au Y.K., Wynn S., Geng G., Chan Y.S., Chan W.Y., Cheung K.M.C. and Fritzsch B., Context
dependent impact of the Y440X campomelic dysplasia Sox9 mutation, ACGA-HKSMG
International Conference on Genetic and Genomic Medicine, |
|
Cheah
K.S.E., Leong
V.Y.L., Gao B., Dung W.F., Leung K.K.H., Wynn S.L., Lau J.Y.B., Niewiadomska A.K., Melhado I.G. and Chan D., Dual roles of Sox |
|
Cheah
K.S.E., Szeto
Y.Y., Au Y.K., Chan Y.S., Lovell-Badge R. and Fritzsch
B., Hearing and balance defects in a mouse model of campomelic dysplasia, Gordon
Research Conference on Craniofacial Morphogenesis and Tissue Regeneration. |
|
Cheah
K.S.E., Insights into the molecular
pathogenesis of Campomelic dysplasia caused by mutations in SOX9. , The
7th Pan Pacific Connective Tissue Societies Symposium, |
|
Cheung C.L., Tang L.F., Sham P.C., McClug P., Chan S.Y., Smith D.K., Su A.I., Cheah K.S.E., Kung A.W.C. and Song Y., Genome-wide Haplotype Association Mapping (HAM) in Mice Leads to an Identification of a Genetic Variant in CER1 Associated with Bone Mineral Density in Premenopausal Women, ASBMR 29th Annual Meeting, Honolulu, Hawaii, USA, September 16-19, 2007. |
|
Cheung C.L., Tang P.L.F., Sham P.C., McClurg P., Chan S.Y., Smith D.K., Su A.I., Cheah K.S.E., Kung A.W.C. and Song Y., Genome-wide haplotype association mapping (HAM) in mice leads to an identification of a genetic variant in CER1 associated with bone mineral density and fracture in southern Chinese women, Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, Hong Kong. 2007. |
|
Cheung
K.M.C., Karppinen J., Chan D., Fan B., Ho D.W.H., Kao P.Y.P., Song Y., Sham P.C., Cheah K.S.E., Leong J.C.Y. and Luk K.D.K., Age-related changes versus
degenerative disc disease. World Forum for Spine Research, World Forum for
Spine Research - The Intervertebral Disc. |
|
Cheung K.M.C., Song Y., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S.P., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Association of the asporin D14 allele with lumbar disc degeneration, Spineweek 2008, Geneva, Switzerland, May 26-31, 2008. |
|
Chik H.H.Y., Chan W.C.W., Cheng Y.W., Tsang K.Y., Cheah K.S.E. and Chan D., Ectopic Expression Of Unfolded Mutant Collagen X In Bone Cells Results In Generalised Hyperostosis in Mice, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Ressort, Cairns, Australia. 2007. |
|
Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Correlating Protein Structure with Disease - Understanding the Mechanism of SEDT, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Ho D.W.H., Cheung K.M.C., Chan D., Cheah K.S.E., Karppinen J., Sham P.C. and Song Y., LINKAGE ANALYSIS WITH SUBSEQUENT FINE-MAPPING ON FAMILIAL EARLY ONSET-DEGENERATIVE DISC DISEASE, SpineWeek 2008, Geneva, SWITZERLAND. 2008. |
|
Ho D.W.H., Cheung K.M.C., Chan D., Karppinene 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, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
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. World Forum for Spine Research., The
Intervertebral Disc. |
|
Ho D.W.H., Cheung K.M.C., Chan D., Cheah K.S.E., Karppinen J., Sham P.C. and Song Y., Linkage analysis with subsequent fine-mapping on familial early onset-degenerative disc disease., Spine Week 2008, Geneva, May 26-31, 2008. |
|
Kao P.Y.P., Chan D., Cheah K.S.E., Cheung K.M.C., Karppinene J., Yip S.P., Sham P.C. and Song Y., Genome-wide Association Study of Degenerative Disc Disease (DDD) , 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Kao P.Y.P., Chan D., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Cheah K.S.E., Song Y. and Sham P.C., Genome-wide association study of degenerative disc disease (DDD)., Spine Week 2008, Geneva, May 26-31, 2008. . 2008. |
|
Kao
P.Y.P., Chan D., Cheah K.S.E., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Song Y. and Sham P.C., Genome-wide association study
of degenerative disc disease (DDD)., World Forum for Spine Research - The
Intervertebral Disc. |
|
Kao P.Y.P., Chan D., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Cheah K.S.E., Song Y., Sham P.C. and Sham P.C., Genome-wide association study of degenerative disc disease, Spineweek 2008, Geneva, Switzerland, May 26-31, 2008. |
|
Kwong
W.H., Wong S.Y.Y., Kao P.Y.P., Fritzsch B. and Cheah K.S.E., An essential role for
type IIA procollagen in mouse inner ear development, 6th Molecular Biology
of Hearing & Deafness Conference. 11-14 July 07, |
|
Lee B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tung L.F., Song Y. and Tanner J.A., Understanding How Polymorphisms in Cerberus-like Result in low Bone Mineral Density, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Li J., Wu Y., Wu E.X., Chan D., Cheah K.S.E. and Zhou Z., Accelerated Senescence in Degenerate Intervertebral Disc of Laminopathy-based Premature Aging Mouse Model, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Lu L., Li X.T., Tai C.P., Huen M.S.Y., Liu D., Cheah K.S.E. and Huang J., Optimization of single stranded oligonucleotide-mediated modification of plasmid DNA., Biotechniques. 2008, 44: 217-20,222,224. |
|
Mak
A.C.Y., Smith D.K., Huang J. and Cheah K.S.E., The Role of SOX |
|
Mok K.L., Sham P.C., Cheah K.S.E., Chin F.Y.L. and Smith D.K., Human Cis-regulatory Module Discovery by Genome Comparison, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Puligilia C., Dabdoub A., Cheah K.S.E. and Pevny L.H., Sox2 as a prosensory and proneural gene in the developing mouse cochlea., Developmental Biology. 2008, 319 535. |
|
Song Y., Ho D.W.H., Karppinen J., Kao P.Y.P., Fan B.J., Luk K.D.K., Yip S.P., Leong J.C.Y., Cheah K.S.E., Sham P.C., Chan D. and Cheung K.M.C., Association between promoter-1607 polymorphism of MMP1 and lumbar disc disease in Southern Chinese, BMC Medical Genetics. 2008, 9(1): 38. |
|
Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S.P., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Association of the asporin D14 allele with lumbar disc degeneration in Asians, American Journal of Human Genetics. 2008, 82(3): 744-747. |
|
Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Genetic Risk Factors For Intervertebral Disc Degeneration, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia, 28 October - 1 November 2007. |
|
Song
Y., Chan D., Kao P.Y.P., Ho D.W.H., Fan B., Karpinen J., Yip S.Y., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Cheung K.M.C., Three genes in the
aggrecan degradation pathway act synergistically to predispose to degenerative
disc disease., World Forum for Spine Research - The Intervertebral Disc. |
|
Szeto
Y.Y., Au Y.K., Wynn S., Chan Y.S., Lovell-Badge R., Chan W.Y.,
Fritzsch B. and Cheah K.S.E.,
A mouse model for hearing and balance defects in campomelic dysplasia, 6th
Molecular Biology of Hearing & Deafness Conference. |
|
Trebicz-Geffen M., Robinson D., Evron Z., Glaser T., Fridkin M., Kollander Y., Vlodavsky I., Ilan N., Law K.F., Cheah K.S.E., Chan D., Werner H. and Nevo Z., The molecular and cellular basis of exostosis formation in hereditary multiple exostoses. , Int J Exp Pathol. . 2008, Epub. |
|
Wong
E.Y.M., Sae-Pang J.J., Mak S.S.,
Ling K.W., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Gain-of-function Hoxb3
mutation affects endothelin-1 pathway in craniofacial development., Gordon
Research Conference on Craniofacial Morphogenesis & Tissue Regeneration, |
|
Wong
E.Y.M., Chan Y.S., Cheah K.S.E. and Sham M.H., The role of Hox genes in
dorsoventral patterning and morphogenesis of inner ear. , Gordon Research
Conference on Auditory System in |
|
Wong
E.Y.M., chan Y.S., Wu D.K. and Cheah
K.S.E., The role of Hox genes in mouse inner ear development, 6th
Molecular Biology of Hearing & Deafness Conference. 11-14 July 07, |
|
Wong
E.Y.M., Chan Y.S., Cheah K.S.E. and Sham M.H., The role of Hox genes in otic
vesicle patterning in Six1 regulatory pathway. , Gordon Research
Conference on Auditory System (Graduate Research Seminar) in |
|
Wong
E.Y.M., Chan Y.S., Wu D., Cheah
K.S.E. and Sham M.H., The
role of HOX genes in mouse inner ear development., The 6thMolecular
Biology of Hearing and Deafness Conference, |
|
Wong Y.F., Kong F.C.F., Cheah K.S.E. and Chow K.L., crm-1facilitates BMP signaling to control body size in Caenorhabditis elegans, Developmental Biology. 2007, 311: 95-105. |
|
Yee
A.F.Y., Melhado I.G., Cheah K.S.E., Cheung K.M.C. and Chan D., Protein expression of the
intervertebral disc: in Health and disease., World Forum for Spine
Research - The Intervertebral Disc. |
|
Yee
A.F.Y., Melhado I.G., Cheah K.S.E., Chan D. and Cheung K.M.C., Use of tandem mass
spectrometry as a tool for proteomics studies in aging and degeneration
processes of the intervertebral disc., Spine Week 2008, |
|
Yee
A.F.Y., Melhado I.G., Cheah K.S.E., Chan D. and Cheung K.M.C., Use of tandem mass
spectrometry as a tool for proteomics studies in aging and degeneration
processes of the intervertebral disc, Spineweek 2008, |
|
Zhu G., Chan D., Cheah K.S.E. and Huang J., KIF5b is Essential for Growth Plate Organization and Cytokinesis, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Chee DMC |
|
List of Research Outputs |
|
Chee
D.M.C., Cheung
M.C.H., Lui V.C.H. and Sham M.H., Role of Conserved Domains in
the Transcriptional Function of Sox |
|
Zhang M., Chee D.M.C., Leung C., Tam P.K.H., Lui V.C.H. and Sham M.H., Generation of Mutant Mouse Models for Studying the Role of Sox10 Functional Domains in Enteric Nervous System Development, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Researcher
: Chen Y |
|
List of Research Outputs |
|
Yung L.M., Wong W.T., Tian X.Y., Leung F.P.,
Lau C.W., Yao X.Q., Chen Y.,
Vanhoutte P.M.G.R. and Huang Y.,
Crauberry juice consumption ameliorates endothelial dysfunction during
estrogen deficiency, Journal of the |
|
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 |
|
Researcher
: Cheng YW |
|
List of Research Outputs |
|
Chik H.H.Y., Chan W.C.W., Cheng Y.W., Tsang K.Y., Cheah K.S.E. and Chan D., Ectopic Expression Of Unfolded Mutant Collagen X In Bone Cells Results In Generalised Hyperostosis in Mice, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Ressort, Cairns, Australia. 2007. |
|
Researcher
: Cheung MCH |
|
List of Research Outputs |
|
Chee
D.M.C., Cheung M.C.H., Lui V.C.H. and Sham M.H., Role of Conserved Domains in
the Transcriptional Function of Sox |
|
Cheung
M.C.H. and Chan
D., Book And Media Reviews title: Principles Of Developmental Genetics,
In: John L. Zeller, MD, PhD Contributing Editor Section Editor: Book and
Media Reviews Journal of the American Medical Association (JAMA) , The
Journal Of The American Medical Association. |
|
Cheung M.C.H., Invited Lecture the Transcriptional Control Of Neural Crest Induction, Survival And Delamination. Froniters In Biomedical Research. , 2007. |
|
Researcher
: Chik HHY |
|
List of Research Outputs |
|
Chik H.H.Y., Chan W.C.W., Cheng Y.W., Tsang K.Y., Cheah K.S.E. and Chan D., Ectopic Expression Of Unfolded Mutant Collagen X In Bone Cells Results In Generalised Hyperostosis in Mice, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Ressort, Cairns, Australia. 2007. |
|
Researcher
: Chin KT |
|
List of Research Outputs |
|
Chan C.P., Chin K.T. and Jin D., N-linked Glycosylation Is Required for Proteolytic Activation of Liver-enrich Transcription Factor CREB-H , 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Ching YP |
|
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 Pak |
|
Project Title: |
Roles of
p21-activated protein kinase (Pak) |
|
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 Pak |
|
Project Title: |
Roles of
p21-activated protein kinase (Pak) |
|
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
Pak |
|
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 |
|
Project Title: |
Molecular
neurobiology: Regulation of p21-activated protein kinase |
|
Investigator(s): |
Ching YP |
|
Department: |
Anatomy |
|
Source(s) of Funding: |
Matching Fund for NSFC Young Researcher Award |
|
Start Date: |
01/2007 |
|
Completion Date: |
12/2009 |
|
Abstract: |
|
To study molecular neurobiology:
regulation of p21-activated protein kinase |
|
Project Title: |
Functional characterisation of a putative tumor suppressor gene, TAX1BP2, in liver cancer |
|
Investigator(s): |
Ching YP |
|
Department: |
Pathology |
|
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
|
Start Date: |
04/2007 |
|
Abstract: |
|
1. Key issues and problem being
addressed: Liver cancer (hepatocellular carcinoma, HCC) is one of the most
common cancers worldwide. The prognosis of HCC patients is often poor because
of the delay in diagnosis and its high recurrence rate after surgery.
Although the risk factors of HCC, such as hepatitis B and C virus infection,
cirrhosis, and dietary aflatoxin are well established, the genetic mechanisms
in the pathogenesis and tumour progression are poorly defined. Chromosome
instability that leads to clonal expansion of genetically altered cells is a
hallmark of cancer and is highly relevant to hepatocarcinogenesis. Thus
characterization of tumor suppressor genes and elucidation of the mechanisms
of chromosome instability are both major challenges in liver cancer research.
2. Purpose of proposed project: Recently, we have identified and
characterized a novel cellular centrosomal protein, which we have named
TAX1BP2 (Ching et al., 2006, Nature cell Biology 8: 717-24). We have
demonstrated that TAX1BP2 plays an important role in the regulation of
centrosome duplication, and dysregulation of TAX1BP2 may lead to aneuplody of
cells. In our preliminary study, we observed that TAX1BP2 is frequently
underexpressed in human HCC (40%) and the underexpression of TAX1BP2
transcript is significantly associated with a poorer prognosis in terms of
shorter overall survival rates. In addition, TAX1BP2 is localized at the
chromosome locus 1p36, which is also a frequently deleted region in HCC. As
HBV infection is a major risk factor of HCC, particularly in this region and
locally, we have found that the HBV viral oncoprotein HBx interacts with
TAX1BP |
|
Researcher
: Choi MY |
|
List of Research Outputs |
|
Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Correlating Protein Structure with Disease - Understanding the Mechanism of SEDT, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Huang Y., Choi M.Y., Au S.W.N., Au D.M., Lam V.M.S. and Engel P.C., Purification and detailed study of two clinically different human glucose 6-phosphate dehydrogenase variants, G6PD(Plymouth) and G6PD (Mahidol): Evidence for defective protein folding as the basis of disease., Mol Genet Metab. 2008. 2008, 93(1): 44-53. |
|
Researcher
: Choy EYW |
|
List of Research Outputs |
|
Choy E.Y.W., A Study Of Epstein-Barr Virus-Encoded Small Regulatory RNAS, PhD Thesis. 2007. |
|
Choy
E.Y.W., Siu
K.L., Kwong D.L.W., Tsao G.S.W. and Jin D., Epstein-Barr virus-encoded
microRNA targets PUMA to promote tumor cell survival , 2008 |
|
Choy
E.Y.W., Siu
K.L., Kwong D.L.W., Tsao G.S.W. and Jin D., First place in poster
competition, 2008 Miami Winter Symposium, A Nature Conference on
Regulatory RNA in Biology and Human Health. |
|
Choy E.Y.W., Kok K.H., Tsao G.S.W. and Jin D., Utility of Epstein-Barr virus-encoded small RNA promoters for driving the expression of fusion transcripts harboring short hairpin RNAs., gne Ther.. 2008, 15: 191-202. |
|
Choy E.Y.W., Kok K.H., Tsao G.S.W. and Jin D., Utility of Epstein-Barr virus-encoded small RNA promoters for driving the expression of fusion transcripts harboring small hairpin RNAs., Gene Therapy. 02/2008, 2007, 15: 191-202. |
|
Researcher
: Chun CS |
|
List of Research Outputs |
|
Wang X., Cheung H.W., Chun C.S., Jin D. and Wong Y.C., Mitotic checkpoint defects in human cancers and their implications to chemotherapy, Frontiers in Bioscience. 2008, 13: 2103-2114. |
|
Researcher
: Dung WF |
|
List of Research Outputs |
|
Chan W.C.W., Zhang J.C.L., Dung W.F., Wong Q., Parmacek M.S., Lau C.P. and Cheah K.S.E., Functional analysis of SM22β by targeted gene deletion in mice. , ACGA-HKSMG International Conference on Genetic and Genomic Medicine, Hong Kong. June 8-11, 2008. . 2008. |
|
Chan
W.C.W., Zhang J.C.L., Dung W.F., Wong Q., Parmacek M.S., Lau C.P. and Cheah K.S.E., Functional analysis of
SM22β by targeted gene deletion in mice., ACGA-HKSMG International
Conference on Genetic and Genomic Medicine, |
|
Cheah
K.S.E., Leong V.Y.L., Gao B., Dung W.F., Leung K.K.H., Wynn S.L., Lau J.Y.B., Niewiadomska A.K., Melhado I.G. and Chan D., Dual roles of Sox |
|
Researcher
: Fan B |
|
List of Research Outputs |
|
Cheung
K.M.C., Karppinen J., Chan D., Fan B., Ho D.W.H., Kao P.Y.P., Song Y., Sham P.C., Cheah K.S.E., Leong J.C.Y. and Luk K.D.K., Age-related changes versus
degenerative disc disease. World Forum for Spine Research, World Forum for
Spine Research - The Intervertebral Disc. |
|
Song
Y., Chan D., Kao P.Y.P., Ho D.W.H., Fan B., Karpinen J., Yip S.Y., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Cheung K.M.C., Three genes in the
aggrecan degradation pathway act synergistically to predispose to
degenerative disc disease., World Forum for Spine Research - The
Intervertebral Disc. |
|
Researcher
: Gao B |
|
List of Research Outputs |
|
Cheah
K.S.E., Leong V.Y.L., Gao B., Dung W.F., Leung K.K.H., Wynn S.L., Lau J.Y.B., Niewiadomska A.K., Melhado I.G. and Chan D., Dual roles of Sox |
|
Researcher
: Garcia-Barcelo MM |
|
Project Title: |
RET regulatory polymorphisms and susceptibility to Hirschsprung's disease |
|
Investigator(s): |
Garcia-Barcelo MM, Tam PKH, Ganster RW |
|
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, Lui VCH, 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. |
|
Project Title: |
Evaluation of PHOX2B mutations in neuroblastoma patients |
|
Investigator(s): |
Garcia-Barcelo MM, Tam PKH, Miao X |
|
Department: |
Surgery |
|
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
|
Start Date: |
01/2007 |
|
Abstract: |
|
Objectives: To evaluate the frequency of PHOX2B mutations in Chinese neuroblastoma patients There is a need to clarify the involvement of PHOX2B in both familial and sporadic NB cases, and assess its role in the genetic network underlying NB. Therefore, we propose to conduct a large-scale PHOX2B mutation screening in the Chinese population. We will also perform functional analysis of the mutations found. This study will be conducted on 150 NB patients of Chinese origin and will be the first study ever conducted on Chinese at such relatively large scale. Background and key issues: Neuroblastoma (NB) is the most common solid tumor of childhood. The only known risk factor is the inheritance of mutations in the PHOX2B gene and still obscure genetic predisposition. The hallmark of NB is its heterogeneous clinical behavior, which correlates with somatic genetic changes in the tumor. These changes have proved useful as prognostic markers and represent the result to a cancer initiation process governed by the constitutive DNA endowment of the patient. There are several lines of evidence indicating the complexity of the genetics underlying this disease: i) PHOX2B germ-line mutations are not present in all hereditable NB cases; ii) predisposing loci identified so far differ in families. Neuroblastoma occasionally arises in patients with genetically determined congenital neural crest disorders such as HSCR and CCHS (PHOX2B association with HSCR was described by the PI) (1,2). The recent identification of PHOX2B as the major disease-causing gene in CCHS pointed to PHOX2B as a candidate gene for both familial and syndromic neuroblastoma (3). Trochet et al. (3) reported missense PHOX2B mutations in both a familial case of neuroblastoma and a patient with neuroblastoma and HSCR. In a study of families with neuroblastoma, Mosse et al. (4) identified a frameshift PHOX2B mutation in one family but found no evidence for mutations in this gene in eight other families. These data suggest that PHOX2B mutations may be involved in neuroblastoma tumorigenesis but that germline mutational events in this gene may not be present in all hereditary neuroblastoma cases. Studies in larger numbers of patients will help to determine the frequency of PHOX2B mutations in genetic and sporadic forms of neuroblastoma. Further work is needed to clarify whether 1) PHOX2B mutations in patients with neuroblastoma result in gain or loss of function and 2) PHOX2B is a partner of alternative genetic events that predispose to tumorigenesis. 1.Garcia-Barcelo M, Sham MH, Lui VC, Chen BL, Ott J, Tam PK 2003 Association study of PHOX2B as a candidate gene for Hirschsprung's disease. Gut 52:563–567 2.Rohrer T, Trachsel D, Engelcke G, Hammer J 2002 Congenital central hypoventilation syndrome associated with Hirschsprung's disease and neuroblastoma: case of multiple neurocristopathies. Pediatr Pulmonol 33:71–76 3.Trochet D, Bourdeau F, Janoueix-Lerosey I, Deville A, de Pontual L, Schleiermacher G, Coze C, Philip N, Frebourg T, Munnich A, Lyonnet S, Delattre O, Amiel J 2004 Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. Am J Hum Genet 74:761–764 |
|
Project Title: |
Functional analysis of RET coding region mutations |
|
Investigator(s): |
Garcia-Barcelo MM, Miao X, Tam PKH |
|
Department: |
Surgery |
|
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
|
Start Date: |
05/2007 |
|
Abstract: |
|
Key issues Hirschsprung’s disease (HSCR)
is a congenital disorder in which there is an absence of ganglion cells in
variable portions of the lower digestive tract. HSCR has a complex pattern of
inheritance and manifests with low, sex-dependent penetrance and variability
in the length of the aganglionosis. Its incidence varies among populations,
being more frequent in Asians. HSCR is oligogenic, always requiring RET
(major gene) and other interacting susceptibility alleles. HSCR mostly presents
sporadically although it can be familial (≈5-20%)(1).
The RET gene, encoding a tyrosine kinase receptor, is the major HSCR gene and
HSCR-associated germ-line variations/mutations are found in coding (CDS) and
non-coding (NCDS) sequences. The normal development of the enteric nervous
system depends on the integrity or/and stoichiometric levels of the RET
protein(2), which reflect the CDS and/or non-CDS composition of RET. While
HSCR RET-NCDS mutations/variants affect regulatory sites and may affect RET
expression(3-5), CDS mutations/variants are spread throughout the gene and
mainly cause loss-of function of the protein. Critically, RET gain-of
function CDS mutations (exons 10, 11 and 13-16) are directly implicated in
hereditary thyroid cancers (Multiple Endocrine Neoplasia type 2, and Familiar
Medullary Thyroid Carcinoma)(6). Importantly, some of these have been found
in families segregating both HSCR and thyroid cancer and may have a dual
effect in the RET protein. For obvious reasons, an elementary but essential
task of The International Hirschsprung’s Disease Consortium (of which we are
participants) is to establish a RET-genotype-phenotype correlation(7). This
is one of the few cases in which a gene identified as causal has been fully
analyzed from a sufficient number of individuals of different ethnic groups
from whom relevant phenotypic and genotypic information is available. Despite
the overwhelming evidence implicating RET variants (CDS and NCDS) in HSCR,
not many have been functionally tested and it is of note that the
identification of RET-dependent modifiers as additional susceptibility
factors in HSCR may depend on the classification of the families by
mutational type in RET(8). Assessment of the functional significance of
HSCR-associated CDS variants/mutations in RET is essential for understanding
i) phenotypic differences, ii) penetrance and recurrence risk estimations,
iii) the mechanistic of the disease. Objectives to be achieved To analyse the
functional significance of 28 CDS RET variations/mutations found in Chinese
HSCR patients. We are particularly interested in R114H since it is found in
10% of the Chinese patients and never been found in the general population,
neither Caucasians nor Chinese. R114H is inherited from unaffected parents
and its high frequency in our population suggests a founder effect. RET-CDS
mutations that appear de novo in sporadic cases are of particular relevance
since its pathogenicity may be determining its penetrance and therefore,
their segregation in future generations. Investigating the mechanisms of pathogenicity
of those HSCR RET mutations located in “cancer” specific domains of the RET
protein are crucial. References 1. Amiel J, Lyonnet S 2001 Hirschsprung
disease, associated syndromes, and genetics: a review. J Med Genet 38:729-739
2. Pachnis V, Durbec P, Taraviras S, Grigoriou M, Natarajan D 1998 III. Role
Of the RET signal transduction pathway in development of the mammalian
enteric nervous system. Am J Physiol 275:G183-G186 3. Emison ES, McCallion
AS, Kashuk CS, Bush RT, Grice E, Lin S, Portnoy ME, Cutler DJ, Green ED,
Chakravarti A |
|
Researcher
: Ho DWH |
|
List of Research Outputs |
|
Cheung
K.M.C., Karppinen J., Chan D., Fan B., Ho D.W.H., Kao P.Y.P., Song Y., Sham P.C., Cheah K.S.E., Leong J.C.Y. and Luk K.D.K., Age-related changes versus
degenerative disc disease. World Forum for Spine Research, World Forum for
Spine Research - The Intervertebral Disc. |
|
Cheung K.M.C., Song Y., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S.P., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Association of the asporin D14 allele with lumbar disc degeneration, Spineweek 2008, Geneva, Switzerland, May 26-31, 2008. |
|
Ho D.W.H., Chan D., Cheung K.M.C., Sham P.C. and Song Y., Family-base linkage and case control association studies, Current Orthopaedics. 2008, 22: 245-250. |
|
Ho D.W.H., Cheung K.M.C., Chan D., Cheah K.S.E., Karppinen J., Sham P.C. and Song Y., LINKAGE ANALYSIS WITH SUBSEQUENT FINE-MAPPING ON FAMILIAL EARLY ONSET-DEGENERATIVE DISC DISEASE, SpineWeek 2008, Geneva, SWITZERLAND. 2008. |
|
Ho D.W.H., Cheung K.M.C., Chan D., Karppinene 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, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
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. World Forum for Spine Research., The
Intervertebral Disc. |
|
Ho D.W.H., Cheung K.M.C., Chan D., Cheah K.S.E., Karppinen J., Sham P.C. and Song Y., Linkage analysis with subsequent fine-mapping on familial early onset-degenerative disc disease., Spine Week 2008, Geneva, May 26-31, 2008. |
|
Kao P.Y.P., Chan D., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Cheah K.S.E., Song Y. and Sham P.C., Genome-wide association study of degenerative disc disease (DDD)., Spine Week 2008, Geneva, May 26-31, 2008. . 2008. |
|
Kao
P.Y.P., Chan D., Cheah K.S.E., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Song Y. and Sham P.C., Genome-wide association study
of degenerative disc disease (DDD)., World Forum for Spine Research - The
Intervertebral Disc. |
|
Kao P.Y.P., Chan D., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Cheah K.S.E., Song Y., Sham P.C. and Sham P.C., Genome-wide association study of degenerative disc disease, Spineweek 2008, Geneva, Switzerland, May 26-31, 2008. |
|
Song Y., Ho D.W.H., Karppinen J., Kao P.Y.P., Fan B.J., Luk K.D.K., Yip S.P., Leong J.C.Y., Cheah K.S.E., Sham P.C., Chan D. and Cheung K.M.C., Association between promoter-1607 polymorphism of MMP1 and lumbar disc disease in Southern Chinese, BMC Medical Genetics. 2008, 9(1): 38. |
|
Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S.P., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Association of the asporin D14 allele with lumbar disc degeneration in Asians, American Journal of Human Genetics. 2008, 82(3): 744-747. |
|
Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Genetic Risk Factors For Intervertebral Disc Degeneration, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia, 28 October - 1 November 2007. |
|
Song
Y., Chan D., Kao P.Y.P., Ho D.W.H., Fan B., Karpinen J., Yip S.Y., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Cheung K.M.C., Three genes in the
aggrecan degradation pathway act synergistically to predispose to
degenerative disc disease., World Forum for Spine Research - The
Intervertebral Disc. |
|
Researcher
: Huang J |
|
Project Title: |
RNA-DNA hybrid oligonucleotide mediated site-specific repair and gene therapy |
|
Investigator(s): |
Huang J |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Matching Fund for Hi-Tech Research and Development
Program of |
|
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: |
Development of an Efficient Recombinant Protein Expression System in Pseudoalteromonas haloplanktis TAC125 |
|
Investigator(s): |
Huang J |
|
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 |
|
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: |
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: |
Role of kinesin-mediated intracellular transportation in Alzheimer's Disease |
|
Investigator(s): |
Huang J, Song Y, 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 |
|
Project Title: |
Towards a visualized proteome of Escherichia coli |
|
Investigator(s): |
Huang J, Smith DK |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
10/2006 |
|
Abstract: |
|
The aim are (1) resources development: generate EGFP-tagged E. coli strain library for systematic analysis of E. coli proteome; (2) functional analysis: characterization of the subcellular localization and dynamics of the E. coli proteome; (3) bioinformatics studies: cataloging and annotating E. coli protein localization information that allows interactive queries, followed by proteomic studies to define the relationships between subcellular sites and protein functions. |
|
Project Title: |
Development of Live Escherichia coli-Mediated Oral Vaccine against Avian Influenza Viruses |
|
Investigator(s): |
Huang J, Zheng B |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Seed Funding Programme for Applied Research |
|
Start Date: |
10/2006 |
|
Abstract: |
|
There are two objectives of this project. The first objective is to establish an integrated recombineering platform for vaccine development and production. The same platform can also be applied for gene therapy and functional genomics studies. Previously, foreign genes are carried in plasmids when live nonpathogenic and attenuated bacteria are used as vaccine carriers. However, there are several defects with the plasmid based systems. (1), plasmids are genetically unstable in an environment without antibiotic pressure. (2), delivery of antibiotic resistant genes into animal or human bodies may potentially be unsafe. (3), high copies of plasmid may by toxic for the host cells. (4), due to the incompatibility of plasmids with the same replication origin, it is difficult to introduce multiple antigens simultaneously to provoke effective immune protection. We plan to create a platform for high level expression of multiple antigen genes in this project. The innovation of the project is the utilization of E. coli chromosome as carrier and expression vector for multiple antigen genes. This can remarkably reduce the cytotoxicity imposed by plasmids and improve the genetic stability of extragenous DNA sequences. A second innovation is the ability to carrier multiple antigens as well as DNA vaccine simultaneously. A third innovation is that recombineering enables robust and rapid construction of bacteria strains as vaccines in respond in a timely fashion to circulating avian influenza viruses. The second objective of the project is a novel bacteria-mediated oral vaccine against avian influenza viruses. Currently, live attenuated viruses and inactivated influenza vaccines are used for the prophylaxis against pandemic influenza. The production of these vaccines involves live viruses. For example, inactivated vaccines are produced by using live virus that is grown in fertile chicken eggs or mammalian cells followed by purification and inactivation using either formaldehyde or β-propiolactone. Although these vaccines are effective and safe in clinical use, there are many problems associated with their production and application. (1), the production processes require large numbers of eggs or mammalian cells that prevent it from responding rapidly to a pandemic event. (2), the costs of vaccine production using egg or mammalian cells are high while the yields are low. (3), it could be very dangerous or even disastrous to produce highly pathogenic avian influenza in large quantities to make the vaccines. (4), the administration methods for these vaccines are intramuscular or hypodermic injection. It requires large amount of man power for immunization in poultry industry, making it less acceptable. Clearly, new methods must be developed to produce vaccines for influenza prevention in poultry and swine industries. In this project, we will develop a novel bacteria-mediated oral vaccine for use in the poultry and swine industries. Specifically, we will integrate multiple AIV antigen genes into the chromosome of E. coli strains we developed previously. These E. coli strains have been modified to invade or adhere to cells along the gastrointestinal or respiratory tracks. Once inside the cells, the bacteria will burst to deliver the protein antigens and any DNA vaccines. This can effectively stimulate the host mucosal and peripheral immune responses. We have also engineered these E. coli strains to be nonpathogenic as demonstrated by our previous studies. The novel bacteria-based vaccines promise robust and rapid production against newly identified/circulating subtypes of avian influenza viruses in epidemic situation. It enables us to be well prepared for new epidemic situations. These vaccines can be formulated for oral inoculation by simply combined with nutritious foods or encapsulated. This will be more convenient and acceptable to use, and be easier to administer. It will save time and money since it does not require large amount of man power for immunization. The bacteria vaccines can be self administered by animals, virtually eliminating the use of hypodermic needles. Compared to the inactivated or live attenuated vaccines, the bacteria based vaccines are easy to manufacture since only culture of non-pathogenic bacteria are needed with no special requirement to equipments. These vaccines have huge market potentials with considerable profit. Achieving the objectives will be a great contribution to human health. |
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Project Title: |
Mutational studies of small noncoding RNAs essential for biofilm formation |
|
Investigator(s): |
Huang J |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
|
Start Date: |
03/2007 |
|
Abstract: |
|
A biofilm is a structured microbial
community of cells enclosed in an extracellular matrix, growing on a
substrate, and displaying phenotypic features different from their planktonic
counterparts (1). Commensal E. coli can form biofilms at body temperature,
and their biofilm-forming ability is positively correlated with relapse of
urinary tract infection (2). However, expression of known biofilm-promoting
factors (including F-like conjugative pili, aggregative adherence fimbriae,
and curli) (3-5) cannot adequately account for the increased biofilm
formation of E. coli isolates in vitro (6), indicating the involvement of
additional yet unknown pathways governing E. coli biofilm formation. With the
identification of many small noncoding RNAs (sncRNAs) in bacterial and other
genomes, it is tempting to speculate that sncRNAs, which regulate expression
of a wide range of essential genes, may be one of such undiscovered biofilm
determinants. A genome contains a set of genes that are transcribed into RNAs
encoding no proteins. Most of these RNAs are small (between 50 and 250 nt in
length) (7) and therefore referred to as small noncoding RNAs. sncRNAs are
widely present in different organisms and have structural, regulatory or
catalytic properties (8). The regulatory functions of sncRNAs, particularly
in bacterial stress responses and virulence (9-11), have drawn much attention
and efforts have been made to search for sncRNAs in bacteria. However, their
small size complicates their detection by biochemical and genetic methods.
They are not translated into proteins and the lack of a translation frame
does not allow identification of frameshifts and nonsense mutations (7). Despite
this, previous studies have reported more than 80 sncRNAs in E. coli, mainly
by analyzing conserved intergenic regions (12-19).A subset of the sncRNAs act
via short, interrupted basepairing interactions with target mRNAs, and lead
to inhibition or stimulation of translation, and mRNA degradation or
stabilization (20). In E. coli, some sncRNAs interact with their targets via
the RNA chaperone Hfq, which interacts strongly with the sncRNAs (21) and
their target-mRNA (22-24). In spite of the crucial role of sncRNAs/mRNA
pairing, only a small number of sncRNAs, such as RyhB (25, 26), OxyS (27,
28), DsrA (29) and MicA (30), have been characterized for their mRNA-targets.
Of particular interest is the involvement of sncRNAs in the overall
construction of a cell's architecture (31). The sncRNAs involved in cell
growth, biofilm formation, and virulence are mostly unknown. The lack of
systematic studies analyzing mRNA targets of sncRNAs warrants further
attempts towards this research field. Therefore, we propose here to identify
the sncRNAs involved in biofilm formation in E. coli.Objectives:(a) Generate
libraries of E. coli cell strains with sncRNA deletion or overexpression; (b)
Screen for sncRNAs that regulate biofilm formation with sncRNA mutant strains
generated in (a). (c) Study the gene expression changes in the sncRNA mutants
defective in biofilm formation.References:1. R. Orme, C. W. Douglas, S.
Rimmer, M. Webb, Proteomics 6, 4269 (Aug, 2006).2. S. M. Soto et al., Clin
Microbiol Infect 12, 1034 (Oct, 2006).3. J. M. Ghigo, Nature 412, 442 (Jul
26, 2001).4. J. Sheikh, S. Hicks, M. Dall'Agnol, A. D. Phillips, J. P.
Nataro, Mol Microbiol 41, 983 (Sep, 2001).5. C. Prigent-Combaret et al.,
Environ Microbiol 2, 450 (Aug, 2000).6. A. Reisner, K. A. Krogfelt, B. M.
Klein, E. L. Zechner, S. Molin, J Bacteriol 188, 3572 (May, 2006).7. R.
Hershberg, |
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List of Research Outputs |
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An X., Lu J., Huang J., Zhang B., Liu D., Chen J., Zhou Y. and Tong Y., Rapid assembly of >multiple-exon cDNA directly from genomic DNA , PLoS ONE. 2007, 2(11): 1179. |
|
Durairajan S.S., Yuan Q.J., Xie L., Chan W.S., Kum W.F., Koo I , Liu C., Song Y., Huang J., Klein W.L. and Li M., Salvianolic acid B inhibits Aβ fibril formation and disaggregates preformed fibrils and protects against Aβ-induced cytotoxicty , Neurochemistry International. 2008, 52: 741-750. |
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Li Z., Yao H., Ma Y., Dong Q., Peng Y., Zheng B., Huang J., Chan C.Y., Lin M.C., Sung J.J., Yuen K.Y., Kung H.F. and He M.L., Inhibition of HBV gene expression and replication by stably expressed interferon-α1 via adeno-associated viral vectors, J Gene Med.. 2008, 10(6): 619-627. |
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Liu C. and Huang J., Salvianoli Acid B Inhibits Hydrogen Peroxide -Induced Endothelial Cell apoptosis Through regulating P13K/Akt Signaling, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Liu C., Xie L.X., Li M., Durairajan S.S.K., Goto S. and Huang J., Salvianolic Acid B Inhibits Hydrogen Peroxide-Induced Endothelial Cell Apoptosis through Regulating PI3K/Akt Signaling., PLoS ONE. 2007, 2(12): 1321. |
|
Lu L., Li X.T., Tai C.P., Huen M.S.Y., Liu D., Cheah K.S.E. and Huang J., Optimization of single stranded oligonucleotide-mediated modification of plasmid DNA., Biotechniques. 2008, 44: 217-20,222,224. |
|
Mak
A.C.Y., Smith D.K., Huang J. and Cheah K.S.E., The Role of SOX |
|
Man S.C., Durairajan S.S.K., Kum W.F., Lu J.H., Huang J., Cheng C.F., Chung V., Xu M. and Li M., Systematic Review of the Efficacy and Safety of Herbal Medicines for Alzheimer's Disease, Journal of Alzheimer's Disease. 2008, 14: 209-223. |
|
Miao Y., Danchin A. and Huang J., Visualizing the Proteome of Escherichia Coli by Recombineering Technology, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Qi S., Sun H. and Huang J., Expression of Mutated Hpn - a Nickel Binding Protein from Helicobacter Pylori, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
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Sun H., Ge R., Zeng Y., Wang H. and Huang J., Histidine-rich Protein, Hpn and Metallothionein: Are they Similar?, 13th International Conference on Biological Inorganic Chemistry (ICBIC-13), Vienna, Austria, July 15-20. 2007. |
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Wang J. and Huang J., Visualizing the Proteome of Escherichia coli by Labeling E. Coli Chromosomal Genes with Fluorescent Tags, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Wang Z., Zhou Z., Liu D. and Huang J., Characterization of single-stranded oligonucleotide-mediated deletion in >mammalian cells., Oligonucleotides. 2008, 18(1): 21-32. |
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Wang Z., Zhang X., Zhu G. and Huang J., Kif5b is Responsible for Muscle Development and Normal Function, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Watt R.M., Huang J., Ho J.W.S. and Chen W., Engineering Bacterial Chromosomes: E. coli and Beyond, Hong Kong-Wuhan University Conjoint Scientific Meeting, Dongguan, China, 10-11th May. 2008. |
|
Yang N., Tanner J.A., Zheng B., Watt R.M., He M.L., Lu L., Jiang J., Shum K.T., Lin Y., Wong K.L., Lin M.C., Kung H.F., Sun H. and Huang J., Bismuth complexes inhibit the SARS coronavirus, Angewandte Chemie International Edition. 2007, 46: 6464-6468. |
|
Yang N., Tanner J.A., Wang Z., Huang J., Zheng B., Zhu N. and Sun H., Inhibition of SARS coronavirus helicase by bismuth complexes, Chemical Communications. 2007, 4413-4415. |
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Yang N., Tanner J.A., Huang J., Zheng B. and Sun H., Inhibition of the SARS coronavirus by Bismuth Compounds, 13th International Conference on Biological Inorganic Chemistry (ICBIC-13), Vienna, Austria, July 15-20. 2007. |
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Zhou J., Huang J., Poon K.M., Chen D., Chan C.S., Ng F., Guan X.Y., Watt R.M., Lu L., Yuen K.Y. and Zheng B., A mechanism underlying susceptibility to HBV infection: HBV down-regulate transferase-1 type I interferon receptor 1 via suppressing poly(ADP-ribose), 2007 International Meeting: The Molecular Biology of Hepatitis B Viruses.. 2007. |
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Zhu G., Chan D., Cheah K.S.E. and Huang J., KIF5b is Essential for Growth Plate Organization and Cytokinesis, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Huen MSY |
|
List of Research Outputs |
|
Lu L., Li X.T., Tai C.P., Huen M.S.Y., Liu D., Cheah K.S.E. and Huang J., Optimization of single stranded oligonucleotide-mediated modification of plasmid DNA., Biotechniques. 2008, 44: 217-20,222,224. |
|
Researcher
: Hui CC |
|
List of Research Outputs |
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Wang X., Wong E.Y.M., Hui C.C. and Sham M.H., Understanding Hindbrain Neurogenesis by Analysis of a Hoxb3Transgenic Mouse Mutant SL2, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Researcher
: Ikegawa S |
|
List of Research Outputs |
|
Cheung K.M.C., Song Y., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S.P., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Association of the asporin D14 allele with lumbar disc degeneration, Spineweek 2008, Geneva, Switzerland, May 26-31, 2008. |
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Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S.P., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Association of the asporin D14 allele with lumbar disc degeneration in Asians, American Journal of Human Genetics. 2008, 82(3): 744-747. |
|
Researcher
: Jiang J |
|
List of Research Outputs |
|
Yang N., Tanner J.A., Zheng B., Watt R.M., He M.L., Lu L., Jiang J., Shum K.T., Lin Y., Wong K.L., Lin M.C., Kung H.F., Sun H. and Huang J., Bismuth complexes inhibit the SARS coronavirus, Angewandte Chemie International Edition. 2007, 46: 6464-6468. |
|
Researcher
: Jin D |
|
Project Title: |
Implementation of theoretical and technical system for disease genomics |
|
Investigator(s): |
Jin D |
|
Department: |
|
|
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: |
Mitotic checkpoint and genomic stability in ovarian cancer |
|
Investigator(s): |
Jin D |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
National Institutes of |
|
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: |
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 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 |
|
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 |
|
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. |
|
Project Title: |
Characterization
of fusion oncoprotein FUS-CREB |
|
Investigator(s): |
Jin D, Sham MH |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
01/2007 |
|
Abstract: |
|
To characterize the transforming activity
of FUS-CREB |
|
Project Title: |
Centrosome amplification and retroviral oncogenesis |
|
Investigator(s): |
Jin D |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
|
Start Date: |
04/2007 |
|
Abstract: |
|
The overall goal of this study is to characterize cellular protein TAX1BP2 and its interaction with human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax. Our working model is that Tax inhibits TAX1BP2 function causing centrosomal amplification and subsequently genome instability. The specific aims of our project are: 1) To identify and characterize new centrosomal TAX1BP2-binding proteins. 2) To explore the mechanisms for TAX1BP2 inhibition of centrosome duplication. 3) To explore the mechanisms for Tax inhibition of TAX1BP2. |
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List of Research Outputs |
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Chan C.P., Chin K.T. and Jin D., N-linked Glycosylation Is Required for Proteolytic Activation of Liver-enrich Transcription Factor CREB-H , 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Ching Y.P., Chan S.F., Jeang K.T. and Jin D., 2007 Faculty Research Output Prize, In: "Retroviral oncoprotein Tax targets coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication" , The University of Hong Kong . Nature Cell Biology, 2007, 8: 717-724. |
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Choy
E.Y.W., Siu K.L., Kwong D.L.W., Tsao G.S.W. and Jin D., Epstein-Barr virus-encoded
microRNA targets PUMA to promote tumor cell survival , 2008 |
|
Choy
E.Y.W., Siu K.L., Kwong D.L.W., Tsao G.S.W. and Jin D., First place in poster
competition, 2008 Miami Winter Symposium, A Nature Conference on
Regulatory RNA in Biology and Human Health. |
|
Choy E.Y.W., Kok K.H., Tsao G.S.W. and Jin D., Utility of Epstein-Barr virus-encoded small RNA promoters for driving the expression of fusion transcripts harboring short hairpin RNAs., gne Ther.. 2008, 15: 191-202. |
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Choy E.Y.W., Kok K.H., Tsao G.S.W. and Jin D., Utility of Epstein-Barr virus-encoded small RNA promoters for driving the expression of fusion transcripts harboring small hairpin RNAs., Gene Therapy. 02/2008, 2007, 15: 191-202. |
|
Chu L.W., Li Y., Tang A.Y.B., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., A Novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer' s disease in Chinese, Am J Med Genet B. 2007, 144(8): 1007-13. |
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Du L., Kao R.Y.T., Zhou Y., He Y., Zhao G., Wong K.L., Jiang S., Yuen K.Y., Jin D. and Zheng B., Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity., Biochem. Biophys. Res. Commun.. 2007, 359(1): 174-179. |
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Du L., Zhao G., Lin Y., Sui H., Chan C.S., Ma S., He Y.X., Jian S., Wu C.Y., Yuen K.Y., Jin D., Zhou Y.S. and Zheng B., Intranasal Vaccination of Recombinant Adeno-Associated Virus Encoding Receptor-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Spike Protein Induces Strong Mucosal Immune Responses and Provides Long-Term Protection against SARS-CoV Infection., Journal of Immunology. 2008, 180(2): 948-956. |
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Du L., Zhao G., Lin Y., Chan C.S., He Y., Jian S., Wu C.Y., Jin D., Yuen K.Y., Zhou Y. and Zheng B., Priming with rAAV encoding RBD of SARS-CoV S protein and boosting with RBD-specific peptides for T cell epitopes elevated humoral and cellular immune responses against SARS-CoV infection, Vaccine. 2008, 26(13): 1644-1651. |
|
Jin
D., Cellular targets of Epstein-Barr
virus-encoded miRNAs, RNAi, siRNA and miRNA 2008, An SMi meeting. |
|
Jin D., Editorial Board Member, 编委, Chinese Journal of Biotechnology. 生物工程学报, 2007. |
|
Jin D. and Li M.F., Mecahnisms of interferon induction and action, 干扰素的诱生和作用机制, Chinese Journal of Experimental and Clinical Virology. 中华实验和临床病毒学杂志, Beijing, 2007, 21: 411-418. |
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Jin D. and Siu Y.T., Requirement for Tax-induced recruitment of TORC family coactivators in transcriptional activation, American Society for Virlogy 26th Annual Meeting, Oregon State University, Corvallis, Oregon, USA. 2007. |
|
Kok K.H., Ching Y.P. and Jin D., Human TRBP and PACT directly interact with each other and form a complex with Dicer to promote the production of small interfering RNA., American Society for Virlogy 26th Annual Meeting, Oregon State University, Corvallis, Oregon, USA. 2007. |
|
Lam Q.L.K., Zheng B., Jin D., Cao X. and Lu L., Leptin induces CD40 expression through the activation of AKT in murine dendritic cells, J Biol Chem. 2007, 38: 27587-27597. |
|
Mak
T.Y., Chan C.P. and Jin D., Regulation of CREB |
|
Ng M.H., Ching Y.P. and Jin D., Identification and Characterization of a Novel Interaction Partner of Centrosomal Coiled-coil Protein TAX1BP2, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Siu Y.T. and Jin D., CREB - a real culprit in oncogenesis, FEBS Journal. Blackwell, 2007, 274: 3224-3232. |
|
Siu Y.T. and Jin D., MEKK1 Phosphorylation of TORC 1 Transcriptional Coactivator, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Tang V.H.M., Siu K.L. and Jin D., Roles of Yeast Peroxiredoxins In Cellular Defence Against DNA Damage, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Tang
V.H.M., Siu K.L. and Jin D., Roles of yeast
peroxiredoxins in cellular defense against DNA damage., Cold Spring Harbor
Laboratory 2007 meeting on Yeast Cell Biology, |
|
Wang X., Cheung H.W., Chun C.S., Jin D. and Wong Y.C., Mitotic checkpoint defects in human cancers and their implications to chemotherapy, Frontiers in Bioscience. 2008, 13: 2103-2114. |
|
Zheng B., Chan K.W., Lin Y., Zhao G., Chan C.S., Zhang H., Chen H., Wong S.S.Y., Lau S.K.P., Woo P.C.Y., Chan K.H., Jin D. and Yuen K.Y., Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus., Proc Natl Acad Sci USA.. 2008, 105(23): 8091-8096. |
|
Researcher
: Jin G |
|
List of Research Outputs |
|
Jin G., Chan J.K.M. and Zhou Z., Genetic approach to Study the Role of MT1-MMP in Tumor Development in Vivo, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Kao PYP |
|
List of Research Outputs |
|
Cheung
K.M.C., Karppinen J., Chan D., Fan B., Ho D.W.H., Kao P.Y.P., Song Y., Sham P.C., Cheah K.S.E., Leong J.C.Y. and Luk K.D.K., Age-related changes versus
degenerative disc disease. World Forum for Spine Research, World Forum for
Spine Research - The Intervertebral Disc. |
|
Kao P.Y.P., Chan D., Cheah K.S.E., Cheung K.M.C., Karppinene J., Yip S.P., Sham P.C. and Song Y., Genome-wide Association Study of Degenerative Disc Disease (DDD) , 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Kao P.Y.P., Chan D., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Cheah K.S.E., Song Y. and Sham P.C., Genome-wide association study of degenerative disc disease (DDD)., Spine Week 2008, Geneva, May 26-31, 2008. . 2008. |
|
Kao
P.Y.P., Chan
D., Cheah K.S.E., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Song Y. and Sham P.C., Genome-wide association study
of degenerative disc disease (DDD)., World Forum for Spine Research - The
Intervertebral Disc. |
|
Kao P.Y.P., Chan D., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Cheah K.S.E., Song Y., Sham P.C. and Sham P.C., Genome-wide association study of degenerative disc disease, Spineweek 2008, Geneva, Switzerland, May 26-31, 2008. |
|
Kwong
W.H., Wong S.Y.Y., Kao P.Y.P., Fritzsch B. and Cheah K.S.E., An essential role for type
IIA procollagen in mouse inner ear development, 6th Molecular Biology of
Hearing & Deafness Conference. 11-14 July 07, |
|
Song
Y., Chan D., Kao P.Y.P., Ho D.W.H., Fan B., Karpinen J., Yip S.Y., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Cheung K.M.C., Three genes in the
aggrecan degradation pathway act synergistically to predispose to
degenerative disc disease., World Forum for Spine Research - The
Intervertebral Disc. |
|
Researcher
: Kok KH |
|
List of Research Outputs |
|
Choy E.Y.W., Kok K.H., Tsao G.S.W. and Jin D., Utility of Epstein-Barr virus-encoded small RNA promoters for driving the expression of fusion transcripts harboring short hairpin RNAs., gne Ther.. 2008, 15: 191-202. |
|
Choy E.Y.W., Kok K.H., Tsao G.S.W. and Jin D., Utility of Epstein-Barr virus-encoded small RNA promoters for driving the expression of fusion transcripts harboring small hairpin RNAs., Gene Therapy. 02/2008, 2007, 15: 191-202. |
|
Kok K.H., Ching Y.P. and Jin D., Human TRBP and PACT directly interact with each other and form a complex with Dicer to promote the production of small interfering RNA., American Society for Virlogy 26th Annual Meeting, Oregon State University, Corvallis, Oregon, USA. 2007. |
|
List of Research Outputs |
|
Kong C.T. and Zhou Z., Defective Self-renewal And Early Cellular Senescence In Premature Aging Mesenchymal Stem Cells, Keystone Symposium - Tumor Suppressors And Stem Cell Biology, 24 - 29 February, Vancouver, British Columbia, Canada. 2008. |
|
Sun Q., Kong C.T., Huang F. and Chan L.C., Aberrant Dendritic Cell Differentiation Initiated by Mll-Een Fusion Gene Does Not Requre Leukaemic Transformation., Journal of Leukocyte Biology. 2008, 83 (1): 173 - 180. |
|
Researcher
: Krishnan V |
|
List of Research Outputs |
|
Krishnan V., Liu B. and Zhou Z., Proficiency of DNA repair networks in stem cells as determinants of aging, Cell Science. 2007, Epub. |
|
Zhang L., Krishnan V. and Zhou Z., Prelamin A compromises DNA Damage-induced Chromatin Relaxation to Promote Genomic Instability and Aging, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Kwok JCF |
|
List of Research Outputs |
|
Yuen Y.L., Kwok J.C.F., Lau J.W.K., Chan Y.S. and Shum D.K.Y., Commissural projection from the vestibular nucleus in rat embryos: role of chondroitin sulfates, Soc. Neuroscience Abstract (U.S.A.): 870.6. 2007. |
|
Researcher
: Kwong WH |
|
List of Research Outputs |
|
Kwong
W.H., Wong
S.Y.Y., Kao P.Y.P., Fritzsch B.
and Cheah K.S.E., An essential role
for type IIA procollagen in mouse inner ear development, 6th Molecular
Biology of Hearing & Deafness Conference. 11-14 July 07, |
|
Researcher
: Lai WL |
|
List of Research Outputs |
|
Lai W.L. and Wong N.S., The PERK/eIF2α signaling pathway of Unfolded Protein Response is essential for N-(4-hydroxyphenyl) retinamide (4HPR)-induced cytotoxicity in cancer cells, Exp Cell Res. 2008, 314(8) pp: 1667-1682. |
|
Lai W.L., The role of unfolded protein response in the cytotoxicity mechanism of N-(4-hydroxyphenyl) retinamide, PhD Thesis. 2008. |
|
Wong
N.S. and Lai W.L., The
role of reactive oxygen species in UPR-mediated cell death, "Cancer
therapeutics: the road ahead" A |
|
Researcher
: Lam VMS |
|
List of Research Outputs |
|
Huang Y., Choi M.Y., Au S.W.N., Au D.M., Lam V.M.S. and Engel P.C., Purification and detailed study of two clinically different human glucose 6-phosphate dehydrogenase variants, G6PD(Plymouth) and G6PD (Mahidol): Evidence for defective protein folding as the basis of disease., Mol Genet Metab. 2008. 2008, 93(1): 44-53. |
|
Researcher
: Lee BBC |
|
List of Research Outputs |
|
Lee B.B.C., Probing the molecular mechanisms of how polymorphisms in Cerberus-like result in low bone mineral density, MPhil thesis. 2007. |
|
Lee B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tung L.F., Song Y. and Tanner J.A., Understanding How Polymorphisms in Cerberus-like Result in low Bone Mineral Density, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Lee S |
|
List of Research Outputs |
|
Chan W.L., Chan D., Lee S., Cheah K.S.E. and Tanner J.A., The Proteomics of Protein Misfolding in Chondrocytes, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Leong JCY |
|
List of Research Outputs |
|
Cheung
K.M.C., Karppinen J., Chan D., Fan B., Ho D.W.H., Kao P.Y.P., Song Y., Sham P.C., Cheah K.S.E., Leong J.C.Y. and Luk K.D.K., Age-related changes versus
degenerative disc disease. World Forum for Spine Research, World Forum for
Spine Research - The Intervertebral Disc. |
|
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. World Forum for Spine Research., The
Intervertebral Disc. |
|
Kao P.Y.P., Chan D., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Cheah K.S.E., Song Y. and Sham P.C., Genome-wide association study of degenerative disc disease (DDD)., Spine Week 2008, Geneva, May 26-31, 2008. . 2008. |
|
Kao
P.Y.P., Chan D., Cheah K.S.E., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Song Y. and Sham P.C., Genome-wide association study
of degenerative disc disease (DDD)., World Forum for Spine Research - The
Intervertebral Disc. |
|
Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Genetic Risk Factors For Intervertebral Disc Degeneration, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia, 28 October - 1 November 2007. |
|
Song
Y., Chan D., Kao P.Y.P., Ho D.W.H., Fan B., Karpinen J., Yip S.Y., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Cheung K.M.C., Three genes in the
aggrecan degradation pathway act synergistically to predispose to
degenerative disc disease., World Forum for Spine Research - The
Intervertebral Disc. |
|
Researcher
: Leong VYL |
|
List of Research Outputs |
|
Chan
C.W., Gantenbein B., Leong V.Y.L.,
Chan D., Lu W.W., Luk K.D.K., Cheung K.M.C. and Ito K., Cell
Repopulation of the Frozen Intervertebral Disc by Bone Marrow-derived Stromal
Cells., World Forum for Spine Research - The Intervertebral Disc. |
|
Cheah
K.S.E., Leong V.Y.L., Gao B., Dung W.F., Leung K.K.H., Wynn S.L., Lau J.Y.B., Niewiadomska A.K., Melhado I.G. and Chan D., Dual roles of Sox |
|
Tam W.K., Cheung K.M.C., Chan D., Leong V.Y.L., Luk K.D.K. and Zhou G.Q., Both HIF-1aand HIF-2aare Present in
Prenatal and Postnatal Nucleus., World Forum for Spine Research - The
Intervertebral Disc. |
|
Researcher
: Leung C |
|
List of Research Outputs |
|
Cai K., Tse L.Y., Leung C., Tam P.K.H., Xu R. and Sham M.H., Suppression of lung tumor growth and metastasis in mice by adeno-associated virus-mediated expression of vasostatin, Clinical Cancer Research. 2008, 14(3): 939-949. |
|
Leung C. and Sham M.H., Anterior/Posterior-specific Properties of Adult Spinal Cord Neural Progenitor Cells, CDB Symposium 2008, RIKEN Center for Developmental Biology, March 24-26, 2008, Kobe, Japan. . 2008. |
|
Leung C., Asia-Pacific Developmental Biology Network (APDBN) , March 2008 Travel Award. 2008. |
|
Leung
C. and Sham
M.H., Heterogeneity of Neural Progenitor Cells in the Adult Mouse Spinal
Cord. , The 6thISSCR Annual Meeting, |
|
Zhang M., Chee D.M.C., Leung C., Tam P.K.H., Lui V.C.H. and Sham M.H., Generation of Mutant Mouse Models for Studying the Role of Sox10 Functional Domains in Enteric Nervous System Development, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Researcher
: Leung CM |
|
List of Research Outputs |
|
Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Periostin interacts with sclerostin and inhibits its antagonistic effect on Wnt signalling, International Bone and Mineral Society (IBMS) Workshop: Bone biology and therapeutics, Davos, Switzerland. 2008. |
|
Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Purification and identification of sclerostin interacting partners: steps towards therapy with aptamer-based inhibitors, HKU 12th Research Postgraduate Symposium. 2007. |
|
Tanner
J.A., Leung C.M., Wong L.Y., Miller A.D. and Shum K.T., New Selection and Delivery
Approaches for Nucleic Acid Aptamers against Proteomic Targets, Human
Proteomics Organisation (HUPO) 2007 Meeting, |
|
Researcher
: Leung CM |
|
List of Research Outputs |
|
Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Periostin interacts with sclerostin and inhibits its antagonistic effect on Wnt signalling, International Bone and Mineral Society (IBMS) Workshop: Bone biology and therapeutics, Davos, Switzerland. 2008. |
|
Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Purification and identification of sclerostin interacting partners: steps towards therapy with aptamer-based inhibitors, HKU 12th Research Postgraduate Symposium. 2007. |
|
Tanner
J.A., Leung C.M., Wong L.Y., Miller A.D. and Shum K.T., New Selection and Delivery
Approaches for Nucleic Acid Aptamers against Proteomic Targets, Human
Proteomics Organisation (HUPO) 2007 Meeting, |
|
Researcher
: Leung GWY |
|
List of Research Outputs |
|
Li
S.K.M., Smith D.K., Leung G.W.Y., Cheung M.S., Lam E.W., Dimri G.P. and Yao K.M., FoxM |
|
Researcher
: Leung KKH |
|
List of Research Outputs |
|
Cheah
K.S.E., Leong V.Y.L., Gao B., Dung W.F., Leung K.K.H., Wynn S.L., Lau J.Y.B., Niewiadomska A.K., Melhado I.G. and Chan D., Dual roles of Sox |
|
Leung K.K.H., Getting The Most Out Of Your Mice And Research Dollars, The Centre For Reproduction, Development & Growth . 2008. |
|
Researcher
: Leung MC |
|
List of Research Outputs |
|
Leung M.C., Gadd153 mRNA Stability, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Leung OYV |
|
List of Research Outputs |
|
Leung O.Y.V., Chan C.H., Ip M.S.M. and Shum D.K.Y., Development of heparin and heparan sulfate from recombinant syndecan-1 as a potential therapeutic for bronchiectasis, Third International Symposium on Healthy Aging: “Improving the Health of an Aging Population” March 1-2, 2008. |
|
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 Col |
|
List of Research Outputs |
|
Tsui
Y.K., Leung Y.L., Kao
R.Y.T., Chan D., Masuda K. and Cheung K.M.C., Identification of
Chemical Compounds for the Treatment of Intervertebral Disc Degeneration with
the Application of High-throughput Screening, World Forum for Spine
Research - The Intervertebral Disc. |
|
Yang
F., Chan D., Leung Y.L., Lu W.W., Luk K.D.K. and Cheung K.M.C., Dynamic Changes of Type
II Collagen in the Degenerated Murine Discs., World Forum for Spine
Research - The Intervertebral Disc. |
|
Researcher
: Li J |
|
List of Research Outputs |
|
Li J., Wu Y., Wu E.X., Chan D., Cheah K.S.E. and Zhou Z., Accelerated Senescence in Degenerate Intervertebral Disc of Laminopathy-based Premature Aging Mouse Model, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Li J., Indian hedgehog Stimulates Chondrocyte Hypertrophic Differentiation in Endochondral Bone Formation, PhD thesis. 2007. |
|
Researcher
: Li M |
|
List of Research Outputs |
|
Li M., Chan Y.S. and Shum D.K.Y., Chondroitin Sulfate Moieties Restrict Migration of Cranial Motor Neurons in the Developing Hindbrain of Rats, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Li M., Jiang L., Ho S.L., Song Y. and Sham P.C., IGG: A tool to integrate GeneChips for genetic studies. , Bioinformatics. 2007, 23(22): 3105-3107. |
|
Li M., Ho S.L., Sham P.C. and Song Y., In Silico Mapping of a Charcot-marie-tooth Disease Gene in a Pedigree of Hong Kong Chinese, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Li M., Chan Y.S. and Shum D.K.Y., The restrictive role of chondroitin sulfate moieties on the migration of cranial motor neurons in rat hindbrain development, Abstracts of Third International Symposium on Healthy Aging - Improving the Health of an Aging Population: 25. March 1-2. 2008. |
|
Researcher
: Li M |
|
List of Research Outputs |
|
Li M., Chan Y.S. and Shum D.K.Y., Chondroitin Sulfate Moieties Restrict Migration of Cranial Motor Neurons in the Developing Hindbrain of Rats, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Li M., Jiang L., Ho S.L., Song Y. and Sham P.C., IGG: A tool to integrate GeneChips for genetic studies. , Bioinformatics. 2007, 23(22): 3105-3107. |
|
Li M., Ho S.L., Sham P.C. and Song Y., In Silico Mapping of a Charcot-marie-tooth Disease Gene in a Pedigree of Hong Kong Chinese, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Li M., Chan Y.S. and Shum D.K.Y., The restrictive role of chondroitin sulfate moieties on the migration of cranial motor neurons in rat hindbrain development, Abstracts of Third International Symposium on Healthy Aging - Improving the Health of an Aging Population: 25. March 1-2. 2008. |
|
Researcher
: Li SKM |
|
List of Research Outputs |
|
Li
S.K.M., Smith
D.K., Leung G.W.Y., Cheung M.S., Lam E.W., Dimri G.P. and Yao K.M., FoxM |
|
Researcher
: Li Y |
|
List of Research Outputs |
|
Chu L.W., Li Y., Tang A.Y.B., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., A Novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer' s disease in Chinese, Am J Med Genet B. 2007, 144(8): 1007-13. |
|
Li Y., Genetic Analysis of Alzheimer's Disease Associated Gene-A Perspective from Abnormal Cholesterol Metabolism, PhD Thesis. 2008. |
|
Researcher
: Liu B |
|
List of Research Outputs |
|
Krishnan V., Liu B. and Zhou Z., Proficiency of DNA repair networks in stem cells as determinants of aging, Cell Science. 2007, Epub. |
|
Liu B., Dr KP Stephen Chang Gold Medal 2006/2007, 2007. |
|
Liu B., Genomic Instability and Accelerated Cellular Sensecence in Laminopathy-based Premature Ageing, PhD thesis. 2007. |
|
Liu B. and Zhou Z., Lamin A/C, laminopathies and premature ageing, Histology and Histopathology. 2008, 23(6): 747-763. |
|
Researcher
: Liu C |
|
List of Research Outputs |
|
Durairajan S.S., Yuan Q.J., Xie L., Chan W.S., Kum W.F., Koo I , Liu C., Song Y., Huang J., Klein W.L. and Li M., Salvianolic acid B inhibits Aβ fibril formation and disaggregates preformed fibrils and protects against Aβ-induced cytotoxicty , Neurochemistry International. 2008, 52: 741-750. |
|
Liu C. and Huang J., Salvianoli Acid B Inhibits Hydrogen Peroxide -Induced Endothelial Cell apoptosis Through regulating P13K/Akt Signaling, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Liu C., Xie L.X., Li M., Durairajan S.S.K., Goto S. and Huang J., Salvianolic Acid B Inhibits Hydrogen Peroxide-Induced Endothelial Cell Apoptosis through Regulating PI3K/Akt Signaling., PLoS ONE. 2007, 2(12): 1321. |
|
Researcher
: Liu D |
|
List of Research Outputs |
|
An X., Lu J., Huang J., Zhang B., Liu D., Chen J., Zhou Y. and Tong Y., Rapid assembly of >multiple-exon cDNA directly from genomic DNA , PLoS ONE. 2007, 2(11): 1179. |
|
Lu L., Li X.T., Tai C.P., Huen M.S.Y., Liu D., Cheah K.S.E. and Huang J., Optimization of single stranded oligonucleotide-mediated modification of plasmid DNA., Biotechniques. 2008, 44: 217-20,222,224. |
|
Wang Z., Zhou Z., Liu D. and Huang J., Characterization of single-stranded oligonucleotide-mediated deletion in >mammalian cells., Oligonucleotides. 2008, 18(1): 21-32. |
|
Researcher
: Liu H |
|
List of Research Outputs |
|
Chan C., Liu H., Chan Y.S. and Shum D.K.Y., 4-O-sulfated Chondroitins Contribute to Axon-restrictive Property in Schwann cell-as-trocyte Encounters, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Researcher
: Liu J |
|
List of Research Outputs |
|
Zhang
Y., Liu J., Chan Y.S. and Shum D.K.Y., Heparanase expression in
Schwann cells as revealed in injured sciatic nerves and dorsal root ganglion
explant culture, . Seventh IBRO World Congress of Neuroscience, |
|
Zhou
M., Wang Y., Lam K.S.L., Tam P.K.H., Hoo R.L.C., Liu J. and Xu A., Increased Vulnerability to Liver
Injury is Associated with Decreased Mitochondrial Activities in Adiponectin
Knockout Mice: Potential Roles of UCP |
|
Researcher
: Liu J |
|
List of Research Outputs |
|
Zhang
Y., Liu J., Chan Y.S. and Shum D.K.Y., Heparanase expression in
Schwann cells as revealed in injured sciatic nerves and dorsal root ganglion
explant culture, . Seventh IBRO World Congress of Neuroscience, |
|
Zhou
M., Wang Y., Lam K.S.L., Tam P.K.H., Hoo R.L.C., Liu J. and Xu A., Increased Vulnerability to Liver
Injury is Associated with Decreased Mitochondrial Activities in Adiponectin
Knockout Mice: Potential Roles of UCP |
|
Researcher
: Lu L |
|
List of Research Outputs |
|
Lu L., Li X.T., Tai C.P., Huen M.S.Y., Liu D., Cheah K.S.E. and Huang J., Optimization of single stranded oligonucleotide-mediated modification of plasmid DNA., Biotechniques. 2008, 44: 217-20,222,224. |
|
Yang N., Tanner J.A., Zheng B., He M.L., Lu L., Jiang J.Q., Shum K.T., Lin Y., Wong K.L. and Lin M.C., Bismuth Complexes Inhibit the SARS Coronvirus, Angew. Chem. Int. Ed. 2007, 46: 6464. |
|
Yang N., Tanner J.A., Zheng B., Watt R.M., He M.L., Lu L., Jiang J., Shum K.T., Lin Y., Wong K.L., Lin M.C., Kung H.F., Sun H. and Huang J., Bismuth complexes inhibit the SARS coronavirus, Angewandte Chemie International Edition. 2007, 46: 6464-6468. |
|
Researcher
: Lu L |
|
List of Research Outputs |
|
Lu L., Li X.T., Tai C.P., Huen M.S.Y., Liu D., Cheah K.S.E. and Huang J., Optimization of single stranded oligonucleotide-mediated modification of plasmid DNA., Biotechniques. 2008, 44: 217-20,222,224. |
|
Yang N., Tanner J.A., Zheng B., He M.L., Lu L., Jiang J.Q., Shum K.T., Lin Y., Wong K.L. and Lin M.C., Bismuth Complexes Inhibit the SARS Coronvirus, Angew. Chem. Int. Ed. 2007, 46: 6464. |
|
Yang N., Tanner J.A., Zheng B., Watt R.M., He M.L., Lu L., Jiang J., Shum K.T., Lin Y., Wong K.L., Lin M.C., Kung H.F., Sun H. and Huang J., Bismuth complexes inhibit the SARS coronavirus, Angewandte Chemie International Edition. 2007, 46: 6464-6468. |
|
Researcher
: Lu L |
|
List of Research Outputs |
|
Lu L., Li X.T., Tai C.P., Huen M.S.Y., Liu D., Cheah K.S.E. and Huang J., Optimization of single stranded oligonucleotide-mediated modification of plasmid DNA., Biotechniques. 2008, 44: 217-20,222,224. |
|
Yang N., Tanner J.A., Zheng B., He M.L., Lu L., Jiang J.Q., Shum K.T., Lin Y., Wong K.L. and Lin M.C., Bismuth Complexes Inhibit the SARS Coronvirus, Angew. Chem. Int. Ed. 2007, 46: 6464. |
|
Yang N., Tanner J.A., Zheng B., Watt R.M., He M.L., Lu L., Jiang J., Shum K.T., Lin Y., Wong K.L., Lin M.C., Kung H.F., Sun H. and Huang J., Bismuth complexes inhibit the SARS coronavirus, Angewandte Chemie International Edition. 2007, 46: 6464-6468. |
|
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 |
|
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 Hoxb |
|
Project Title: |
Functional
analysis of Hoxb |
|
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-hoxb |
|
Project Title: |
Investigation of cell autonomous function of Hedgehog signaling on vagal neural crest cells by conditional knockout of Smoothened in mice |
|
Investigator(s): |
Lui VCH, Ngan ESW, Tam PKH, Sham MH |
|
Department: |
Surgery |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
01/2007 |
|
Abstract: |
|
(1) Cross floxed Smo mice with a vagal NCC specific cre mouse strain (b3-IIIa-cre); (2) analyze the abnormal phenotypes in the developing ENs of the transgenic mutant mice; (3) analyze the effects of mesenchyme-derived factors on NCCs of the transgenic mutant mice. |
|
Project Title: |
Investigation of the moleular interactions of HOXB5 and RET gene promoter |
|
Investigator(s): |
Lui VCH, Garcia-Barcelo MM, Tam PKH |
|
Department: |
Surgery |
|
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
|
Start Date: |
03/2007 |
|
Abstract: |
|
PURPOSE: To investigate the HOXB5
regulation on the expression of RET receptor tyrosine kinase gene. KEY ISSUES:
The enteric nervous system (ENS) is composed of interconnecting ganglia of
neurons and glia within the gut wall, controlling the intestinal peristalsis.
In mammals, vagal neural crest cells (NCCs) migrate from the neural tube,
enter the foregut and colonize the entire length of the intestine
rostro-caudally, differentiating into neurons and glia(1-5). Defective ENS
development could result in fewer (hypoganglionosis), and/or absence of
enteric ganglia (aganglionosis) affecting the distal intestine as seen in
Hirschsprung’s disease (HSCR). Patients with abnormal ENS develop intestinal
obstruction due to defective intestinal peristalsis. HSCR displays strong
racial variation in the incidence, with the highest frequency among Asians
(2.8 per 10,000 life births)(6). Homeobox (Hox) genes represented the
clustered group of homoebox genes crucial to embryo patterning and cell fate.
In mammals, 39 Hox genes located in 4 chromosomal clusters (A, B, C and D)
are organized in 13 paralogous groups(7). Hox protein functions as
transcriptional activators by binding to target DNA via its homeodomain and
activates target genes transcription. HOXB5 displays a distinct pattern of
expression in mouse and human embryonic gut, suggesting a unique role of HOXB |
|
List of Research Outputs |
|
Chee
D.M.C., Cheung M.C.H., Lui V.C.H. and Sham M.H., Role of Conserved Domains in
the Transcriptional Function of Sox |
|
Zhang M., Chee D.M.C., Leung C., Tam P.K.H., Lui V.C.H. and Sham M.H., Generation of Mutant Mouse Models for Studying the Role of Sox10 Functional Domains in Enteric Nervous System Development, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Researcher
: Mak ACY |
|
List of Research Outputs |
|
Mak
A.C.Y., Smith
D.K., Huang J. and Cheah K.S.E., The Role of SOX |
|
Researcher
: Mak TY |
|
List of Research Outputs |
|
Mak
T.Y., Chan
C.P. and Jin D., Regulation of
CREB |
|
Researcher
: Melhado IG |
|
List of Research Outputs |
|
Cheah
K.S.E., Leong V.Y.L., Gao B., Dung W.F., Leung K.K.H., Wynn S.L., Lau J.Y.B., Niewiadomska A.K., Melhado I.G. and Chan D., Dual roles of Sox |
|
Yee
A.F.Y., Melhado I.G., Cheah K.S.E., Cheung K.M.C. and Chan D., Protein expression of the
intervertebral disc: in Health and disease., World Forum for Spine
Research - The Intervertebral Disc. |
|
Yee
A.F.Y., Melhado I.G., Cheah K.S.E., Chan D. and Cheung K.M.C., Use of tandem mass
spectrometry as a tool for proteomics studies in aging and degeneration
processes of the intervertebral disc., Spine Week 2008, |
|
Yee
A.F.Y., Melhado I.G., Cheah K.S.E., Chan D. and Cheung K.M.C., Use of tandem mass
spectrometry as a tool for proteomics studies in aging and degeneration
processes of the intervertebral disc, Spineweek 2008, |
|
Researcher
: Miao Y |
|
List of Research Outputs |
|
Miao Y., Danchin A. and Huang J., Visualizing the Proteome of Escherichia Coli by Recombineering Technology, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Mok KL |
|
List of Research Outputs |
|
Mok K.L., Computational discovery of Cis-Regulatory Modules In Human Genome By Genome Comparison, MPhil. 2008. |
|
Mok K.L., Sham P.C., Cheah K.S.E., Chin F.Y.L. and Smith D.K., Human Cis-regulatory Module Discovery by Genome Comparison, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Ng MH |
|
List of Research Outputs |
|
Ng M.H., Ching Y.P. and Jin D., Identification and Characterization of a Novel Interaction Partner of Centrosomal Coiled-coil Protein TAX1BP2, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Ng VCW |
|
List of Research Outputs |
|
Chan W.C.W., Ng V.C.W., Cheah K.S.E. and Chan D., Molecular Basis For Growth Plate Abnormalities In A Mouse Model With Schmid Metaphyseal Chondrodyplasia, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia, 28 October - 1 November 2007. |
|
Chan W.C.W., Ng V.C.W., Cheah K.S.E. and Chan D., Molecular Basis For Growth Plate Abnormalities In A Mouse Model With Schmid Metaphyseal Chondrodyplasia, Best Poster Award, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia. 2007. |
|
Researcher
: Ni Y |
|
List of Research Outputs |
|
Ni Y., 2007 Debio-ccrf China Prize, Encouraging Prize, 2007年德彪-CCRF中國獎鼓勵獎, 2007. |
|
List of Research Outputs |
|
Cheah
K.S.E., Leong V.Y.L., Gao B., Dung W.F., Leung K.K.H., Wynn S.L., Lau J.Y.B., Niewiadomska A.K., Melhado I.G. and Chan D., Dual roles of Sox |
|
Researcher
: Poon SCS |
|
List of Research Outputs |
|
Cheung K.M.C., Song Y., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S.P., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Association of the asporin D14 allele with lumbar disc degeneration, Spineweek 2008, Geneva, Switzerland, May 26-31, 2008. |
|
Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S.P., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Association of the asporin D14 allele with lumbar disc degeneration in Asians, American Journal of Human Genetics. 2008, 82(3): 744-747. |
|
Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Genetic Risk Factors For Intervertebral Disc Degeneration, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia, 28 October - 1 November 2007. |
|
Researcher
: Qi S |
|
List of Research Outputs |
|
Qi S., Sun H. and Huang J., Expression of Mutated Hpn - a Nickel Binding Protein from Helicobacter Pylori, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Researcher
: Sae-Pang JJ |
|
List of Research Outputs |
|
Wong
E.Y.M., Sae-Pang J.J., Mak
S.S., Ling K.W., Chan W.Y., Chung S.K.,
Cheah K.S.E. and Sham M.H., Gain-of-function Hoxb3
mutation affects endothelin-1 pathway in craniofacial development., Gordon
Research Conference on Craniofacial Morphogenesis & Tissue Regeneration, |
|
Researcher
: Scharner J |
|
List of Research Outputs |
|
Scharner J., The Role of Adult Stem Cell Integrity in Zmpste 24 based Premature Aging, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Sham MH |
|
Project Title: |
Hoxb3lacZ:
a mutant mouse model for studying the roles of Hoxb |
|
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: |
Genetic and developmental defects of a mouse mutant Mcc with microphthalmia, cataract and closed eyelid |
|
Investigator(s): |
Sham MH, Song Y |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
09/2006 |
|
Abstract: |
|
To identify the Mcc mutant gene locus by fine mapping and to determine the mutation which cause the abnormal eye phenotypes; to characterize the developmental defects of the Mcc mutant eye and lens during embryonic, postnatal and adult stages at the cellular and molecular levels, in order to correlate the genotype with the phenotype. |
|
List of Research Outputs |
|
Cai K., Tse L.Y., Leung C., Tam P.K.H., Xu R. and Sham M.H., Suppression of lung tumor growth and metastasis in mice by adeno-associated virus-mediated expression of vasostatin, Clinical Cancer Research. 2008, 14(3): 939-949. |
|
Chee
D.M.C., Cheung M.C.H., Lui V.C.H. and Sham M.H., Role of Conserved Domains
in the Transcriptional Function of Sox |
|
Leung C. and Sham M.H., Anterior/Posterior-specific Properties of Adult Spinal Cord Neural Progenitor Cells, CDB Symposium 2008, RIKEN Center for Developmental Biology, March 24-26, 2008, Kobe, Japan. . 2008. |
|
Leung
C. and Sham M.H.,
Heterogeneity of Neural Progenitor Cells in the Adult Mouse Spinal Cord. , The
6thISSCR Annual Meeting, |
|
Lui V.C.H., Cheng W.C., Leon Y.Y., Lau K.C., Garcia-Barcelo M.M., Miao X., Kam K.M., So M.T., Chen Y., Wall N.A., Sham M.H. and Tam P.K.H., Perturbation of Hoxb5 signaling in vagal neural crests down-regulates ret leading to intestinal hypoganglionosis in mice., Gastroenterology. 2008, 134(4): 1104-1115. |
|
Ngan E.S.W., Shum K.Y., Poon H.C., Sham M.H., Garcia-Barcelo M.M., Lui V.C.H. and Tam P.K.H., Prokineticin-1 (Prok-1) works coordinately with glial cell line-derived neurotrophic factor (GDNF) to mediate proliferation and differentiation of enteric neural crest cells, Biochimica et Biophysica Acta. 2008, 1783: 467-478. |
|
Poon H.C., Ngan E.S.W., Sit Y.L.F., Hui C.C., Wainwright B.J., Sham M.H., Tam P.K.H. and Lui V.C.H., Conditional Ptc1 knockout in vagal neural crest cells causes a reduced proliferation of enteric nervous system progenitors and intestinal hypoganglionosis, 41st Annual Meeting for the Japanese Society of Developmental Biologists. 2008. |
|
Sham
M.H., A mouse model of congenital cataract , The
7th International Symposium of Ophthalmology Hong Kong, |
|
Wang X., Wong E.Y.M., Hui C.C. and Sham M.H., Understanding Hindbrain Neurogenesis by Analysis of a Hoxb3Transgenic Mouse Mutant SL2, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Wong
E.Y.M., Sae-Pang J.J., Mak S.S.,
Ling K.W., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Gain-of-function Hoxb3
mutation affects endothelin-1 pathway in craniofacial development., Gordon
Research Conference on Craniofacial Morphogenesis & Tissue Regeneration, |
|
Wong
E.Y.M., Chan Y.S., Cheah K.S.E. and Sham M.H., The role of Hox genes in
dorsoventral patterning and morphogenesis of inner ear. , Gordon Research
Conference on Auditory System in |
|
Wong
E.Y.M., Chan Y.S., Cheah K.S.E. and Sham M.H., The role of Hox genes in
otic vesicle patterning in Six1 regulatory pathway. , Gordon Research
Conference on Auditory System (Graduate Research Seminar) in |
|
Wong
E.Y.M., Chan Y.S., Wu D., Cheah
K.S.E. and Sham M.H., The
role of HOX genes in mouse inner ear development., The 6thMolecular
Biology of Hearing and Deafness Conference, |
|
Zhang M., Chee D.M.C., Leung C., Tam P.K.H., Lui V.C.H. and Sham M.H., Generation of Mutant Mouse Models for Studying the Role of Sox10 Functional Domains in Enteric Nervous System Development, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
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, Chen RYL, Ng KP |
|
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 |
|
Project Title: |
Optimal design of genome-wide association studies for multifactorial diseases |
|
Investigator(s): |
Sham PC, Ng MKP, Tang NLS |
|
Department: |
Psychiatry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
01/2007 |
|
Abstract: |
|
To focus on the following issues in the design of genome-wide association studies: (1) multi-stage, multi-platform study designs; (2) function-informed selection of tag SNPs and haplotype tagging; to quantitative evaluation of subject informativeness; marker-based derivation of homogeneous sub-populations. |
|
List of Research Outputs |
|
Ho D.W.H., Cheung K.M.C., Chan D., Karppinene 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, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Kao P.Y.P., Chan D., Cheah K.S.E., Cheung K.M.C., Karppinene J., Yip S.P., Sham P.C. and Song Y., Genome-wide Association Study of Degenerative Disc Disease (DDD) , 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Li M., Ho S.L., Sham P.C. and Song Y., In Silico Mapping of a Charcot-marie-tooth Disease Gene in a Pedigree of Hong Kong Chinese, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Mok K.L., Sham P.C., Cheah K.S.E., Chin F.Y.L. and Smith D.K., Human Cis-regulatory Module Discovery by Genome Comparison, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Shea GKH |
|
List of Research Outputs |
|
Tsui Y.P., Shea G.K.H., Chan Y.S. and Shum D.K.Y., Preparations of Chitosan Support for Cultures of Schwann Cells and Transdifferentiated Mesenchymal Stem Cells, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
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: |
Roles of chondroitin sulfates in axonal growth and patterning in the developing hindbrain |
|
Investigator(s): |
Shum DKY, Chan YS, |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
09/2006 |
|
Abstract: |
|
To test for change in sulfation pattern
of hindrain CS with change in expression of chondroitin sulfotransferases in
the hindbrain during vestibular neurogenesis and axonal projection; to test
that projection of the vestibular commissure is dependent on facilitation by C6ST
expressing cells in the axon-restrictive hindbrain matrix; |
|
Project Title: |
Therapeutic heparan sulfate preparations to address elastase/antielastase imbalance in chronic inflammation |
|
Investigator(s): |
Shum DKY, Ip MSM |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Seed Funding Programme for Applied Research |
|
Start Date: |
11/2006 |
|
Abstract: |
|
The persistent proteolytic activity of
inflammatory wound fluids has been regarded as the consequence of deficient
anti-proteases, and thus the long-held mis-perception of
protease/anti-protease imbalance. In patients with bronchiectasis, we
reported persistent activity of neutrophil elastase despite abundance of
anti-elastases in the bronchial secretions (Shum et al., 2000). We further
traced the cause to shed forms of syndecan |
|
List of Research Outputs |
|
Ao Q., Wang A.J., Chen G.Q., Zuo H.C., Zhang X.F., Fung C.K., Tsui Y., Shum D.K.Y. and Chan Y.S., Fabrication and characterization of multi-channel chitosan nerve conduit and its potential application, Abstracts of Third International Symposium on Healthy Aging - Improving the Health of an Aging Population: 30. March 1-2. 2008. |
|
Chan C., Liu H., Chan Y.S. and Shum D.K.Y., 4-O-sulfated Chondroitins Contribute to Axon-restrictive Property in Schwann cell-as-trocyte Encounters, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Chan C.H., Shum D.K.Y., Tipoe G.L., Mak J.C.W., Leung T.M. and Ip M.S.M., Upregulation of ICAM-1 expression in bronchial epithelial cells by airway secretions in bronchiectasis, Respiratory Medicine. 2008, 102: 287-298. |
|
Fung C.K., Shum D.K.Y. and Chan Y.S., Derivation of Schwann cell from mammalian skin for use in axonal degeneration, Abstracts of Third International Symposium on Healthy Aging - Improving the Health of an Aging Population: 16. March 1-2. 2008. |
|
Lai S.K., Wong T.P., Yung W.H., Shum D.K.Y. and Chan Y.S., Maturation profile of ionotropic glutamate receptors in central vestibular neurons of rats. Journal of Neurochemistry 106 Suppl: 43-44. , 8th Biennial Meeting of Asia-Pacific Society for Neurochemistry. Shanghai, June 24-26. 2008. |
|
Leung O.Y.V., Chan C.H., Ip M.S.M. and Shum D.K.Y., Development of heparin and heparan sulfate from recombinant syndecan-1 as a potential therapeutic for bronchiectasis, Third International Symposium on Healthy Aging: “Improving the Health of an Aging Population” March 1-2, 2008. |
|
Li M., Chan Y.S. and Shum D.K.Y., Chondroitin Sulfate Moieties Restrict Migration of Cranial Motor Neurons in the Developing Hindbrain of Rats, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Li M., Chan Y.S. and Shum D.K.Y., The restrictive role of chondroitin sulfate moieties on the migration of cranial motor neurons in rat hindbrain development, Abstracts of Third International Symposium on Healthy Aging - Improving the Health of an Aging Population: 25. March 1-2. 2008. |
|
Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Differential involvement of perineuronal net components in functional modifications of rat vesticular nucelar neurons, Abstracts of Third International Symposium on Healthy Aging - Improving the Health of an Aging Population: 3. March 1-2. 2008. |
|
Ma
C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Modifications in perineuronal
nets of rat vestibular nuclear neurons during postnatal development and in
injury, 30th Annual Meeting of Japan Neuroscience Society. |
|
Shea G.K.H., Tsui Y., Chan Y.S. and Shum D.K.Y., Functional study of stem-cell-derived Schwann cells using an in-vitro dorsal root ganglia model. Abstracts of Third International Symposium on Healthy Aging, Improving the Health of an Aging Population. 2008, 17. |
|
Shum D.K.Y., Chan C., Liu H.Y., Chau C.H. and Chan Y.S., Addressing the pericellular matrix of reactive astrocytes. , Abstracts of Croucher Advanced Study Institute: Innovative Therapies of Movement Disorders, D12. HK. Nov. 27-30. 2007. |
|
Tam
K.W., Li R.A., Chan Y.S. and Shum D.K.Y., Cloning, recombinant
expression and digestion product characterization of chondroitinse ABC I and
II, Seventh IBRO World Congress of Neuroscience, Melbourne, Australia,
July 12-17. |
|
Tam K.W., Li R.A., Chan Y.S. and Shum D.K.Y., Effects of oligosaccharide products on activity of chondroitin sulphate ABC lyase I – Towards improving the efficacy of the enzyme for in vivo treatment, Abstracts of Third International Symposium on Healthy Aging - Improving the Health of an Aging Population: 4. March 1-2. 2008. |
|
Tse Y.C., Lai C.H., Lai S.K., Liu J.X., Yung K.K.L., Shum D.K.Y. and Chan Y.S., Developmental expression of NMDA and AMPA receptor subunits in vestibular nuclear neurons that encode gravity-related horizontal orientations. , Journal of Comparative Neurology. 2008, 508: 343-364. |
|
Tsui Y., Shea G.K.H., Chan Y.S. and Shum D.K.Y., Schwann cells derived from bone marrow stromal cells – in vitro study with dorsal root ganglia and in vitro study with peripheral nerve conduits, Abstracts of Third International Symposium on Healthy Aging - Improving the Health of an Aging Population: 19. March 1-2. 2008. |
|
Tsui Y.P., Shea G.K.H., Chan Y.S. and Shum D.K.Y., Preparations of Chitosan Support for Cultures of Schwann Cells and Transdifferentiated Mesenchymal Stem Cells, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Yuen Y.L., Kwok J.C.F., Lau J.W.K., Chan Y.S. and Shum D.K.Y., Commissural projection from the vestibular nucleus in rat embryos: role of chondroitin sulfates, Soc. Neuroscience Abstract (U.S.A.): 870.6. 2007. |
|
Zhang
Y., Liu J., Chan Y.S. and Shum D.K.Y., Heparanase expression in
Schwann cells as revealed in injured sciatic nerves and dorsal root ganglion
explant culture, . Seventh IBRO World Congress of Neuroscience, |
|
Zhang
Y., Chau C.H., Lai C.H., Chan Y.S. and Shum D.K.Y., Heparanase upregulation
in astrocytes and macrophages recruited to the injured spinal cord.
Neuroscience Research 58: S145, 30th Annual Meeting of |
|
Researcher
: Shum KT |
|
List of Research Outputs |
|
Shum K.T. and Tanner J.A., In vitro aptamer selection against the SARS Coronavirus Helicase, Annual Symposium of the Hong Kong Proteomics Society. 2007. |
|
Shum K.T., Miller A.D. and Tanner J.A., In vitro aptamer selection against the SARS coronavirus helicase and their intracellular delivery, Oligonucleotide Therapeutics Society Third Annual Meeting, Berlin, Germany. 2007. |
|
Shum K.T. and Tanner J.A., Selection and Delivery of Aptamers Against the SARS Coronavirus Helicase, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Shum K.T. and Tanner J.A., Selection and Delivery of Aptamers against the SARS Coronavirus Helicase, HKU 12th Research Postgraduate Symposium. 2007. |
|
Tanner
J.A., Leung C.M., Wong L.Y., Miller A.D. and Shum K.T., New Selection and
Delivery Approaches for Nucleic Acid Aptamers against Proteomic Targets, Human
Proteomics Organisation (HUPO) 2007 Meeting, |
|
Yang N., Tanner J.A., Zheng B., He M.L., Lu L., Jiang J.Q., Shum K.T., Lin Y., Wong K.L. and Lin M.C., Bismuth Complexes Inhibit the SARS Coronvirus, Angew. Chem. Int. Ed. 2007, 46: 6464. |
|
Yang N., Tanner J.A., Zheng B., Watt R.M., He M.L., Lu L., Jiang J., Shum K.T., Lin Y., Wong K.L., Lin M.C., Kung H.F., Sun H. and Huang J., Bismuth complexes inhibit the SARS coronavirus, Angewandte Chemie International Edition. 2007, 46: 6464-6468. |
|
Researcher
: Shum KT |
|
List of Research Outputs |
|
Shum K.T. and Tanner J.A., In vitro aptamer selection against the SARS Coronavirus Helicase, Annual Symposium of the Hong Kong Proteomics Society. 2007. |
|
Shum K.T., Miller A.D. and Tanner J.A., In vitro aptamer selection against the SARS coronavirus helicase and their intracellular delivery, Oligonucleotide Therapeutics Society Third Annual Meeting, Berlin, Germany. 2007. |
|
Shum K.T. and Tanner J.A., Selection and Delivery of Aptamers Against the SARS Coronavirus Helicase, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Shum K.T. and Tanner J.A., Selection and Delivery of Aptamers against the SARS Coronavirus Helicase, HKU 12th Research Postgraduate Symposium. 2007. |
|
Tanner
J.A., Leung C.M., Wong L.Y., Miller A.D. and Shum K.T., New Selection and
Delivery Approaches for Nucleic Acid Aptamers against Proteomic Targets, Human
Proteomics Organisation (HUPO) 2007 Meeting, |
|
Yang N., Tanner J.A., Zheng B., He M.L., Lu L., Jiang J.Q., Shum K.T., Lin Y., Wong K.L. and Lin M.C., Bismuth Complexes Inhibit the SARS Coronvirus, Angew. Chem. Int. Ed. 2007, 46: 6464. |
|
Yang N., Tanner J.A., Zheng B., Watt R.M., He M.L., Lu L., Jiang J., Shum K.T., Lin Y., Wong K.L., Lin M.C., Kung H.F., Sun H. and Huang J., Bismuth complexes inhibit the SARS coronavirus, Angewandte Chemie International Edition. 2007, 46: 6464-6468. |
|
Researcher
: Siu KL |
|
List of Research Outputs |
|
Choy
E.Y.W., Siu K.L., Kwong D.L.W., Tsao G.S.W. and Jin D., Epstein-Barr virus-encoded
microRNA targets PUMA to promote tumor cell survival , 2008 |
|
Choy
E.Y.W., Siu K.L., Kwong D.L.W., Tsao G.S.W. and Jin D., First place in poster
competition, 2008 Miami Winter Symposium, A Nature Conference on
Regulatory RNA in Biology and Human Health. |
|
Tang V.H.M., Siu K.L. and Jin D., Roles of Yeast Peroxiredoxins In Cellular Defence Against DNA Damage, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Tang
V.H.M., Siu K.L. and Jin D., Roles of yeast peroxiredoxins in
cellular defense against DNA damage., Cold Spring Harbor Laboratory 2007
meeting on Yeast Cell Biology, |
|
List of Research Outputs |
|
Jin D. and Siu Y.T., Requirement for Tax-induced recruitment of TORC family coactivators in transcriptional activation, American Society for Virlogy 26th Annual Meeting, Oregon State University, Corvallis, Oregon, USA. 2007. |
|
Siu Y.T. and Jin D., CREB - a real culprit in oncogenesis, FEBS Journal. Blackwell, 2007, 274: 3224-3232. |
|
Siu Y.T. and Jin D., MEKK1 Phosphorylation of TORC 1 Transcriptional Coactivator, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
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 |
|
Cheung C.L., Tang L.F., Sham P.C., McClug P., Chan S.Y., Smith D.K., Su A.I., Cheah K.S.E., Kung A.W.C. and Song Y., Genome-wide Haplotype Association Mapping (HAM) in Mice Leads to an Identification of a Genetic Variant in CER1 Associated with Bone Mineral Density in Premenopausal Women, ASBMR 29th Annual Meeting, Honolulu, Hawaii, USA, September 16-19, 2007. |
|
Li
S.K.M., Smith D.K., Leung G.W.Y., Cheung M.S., Lam E.W., Dimri G.P. and Yao K.M., FoxM |
|
Mak
A.C.Y., Smith D.K., Huang J. and Cheah K.S.E., The Role of SOX |
|
Mok K.L., Sham P.C., Cheah K.S.E., Chin F.Y.L. and Smith D.K., Human Cis-regulatory Module Discovery by Genome Comparison, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Yap D.Y.L., Smith D.K., Zhang X.W. and Hill J., Using biomarker signature patterns for an mRNA molecular diagnostic of mouse embryonic stem cell differentiation state. , BMC Genomics. 2007, 8: 210. |
|
Yap Y.L., Zhang X.W., Smith D.K., Soong R. and Hill J., Molecular Gene Expression Signature Patterns for Gastric Cancer Diagnosis. , Computational Biology and Chemistry . 2007, 31: 275-287. |
|
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: |
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 |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
01/2005 |
|
Abstract: |
|
Biomarkers detection; detection possible
ALS modifier on chromosome |
|
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: |
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 |
|
List of Research Outputs |
|
Au W.Y., Pang A.W.K., Lam K.Y., Song Y., Lam W.M., So J.C.C. and Kwong Y.L., G6PD deficiency from lyonization after hematopoietic stem cell transplantation from female heterozygous donors, Bone Marrow Transplantation. 2007, 40(7): 677-681. |
|
Chai
L., Leung W.K., Zee K.Y. and Song Y., Association between FCGR |
|
Chan
Y.K., Ching C.Y.J., Xu M.S., Cheung A.N.Y., Yip S.P., Lam L.Y.C., Lai
S.T., |
|
Cheung B.M.Y., Ong K.L., Leung Y.H., Wong Y.F., Song Y. and Sham P.C., Single-nucleotide polymorphisms near the microsatellite D17S1303 and the development of hypertension in a 6-year longitudinal study. , J Hum Hypertens. . 2007, [Epub ahead of print]. |
|
Cheung C.L., Tang L.F., Sham P.C., McClug P., Chan S.Y., Smith D.K., Su A.I., Cheah K.S.E., Kung A.W.C. and Song Y., Genome-wide Haplotype Association Mapping (HAM) in Mice Leads to an Identification of a Genetic Variant in CER1 Associated with Bone Mineral Density in Premenopausal Women, ASBMR 29th Annual Meeting, Honolulu, Hawaii, USA, September 16-19, 2007. |
|
Cheung C.L., Tang P.L.F., Sham P.C., McClurg P., Chan S.Y., Smith D.K., Su A.I., Cheah K.S.E., Kung A.W.C. and Song Y., Genome-wide haplotype association mapping (HAM) in mice leads to an identification of a genetic variant in CER1 associated with bone mineral density and fracture in southern Chinese women, Hong Kong Society of Endocrinology, Metabolism and Reproduction Annual Scientific Meeting, Hong Kong. 2007. |
|
Cheung
K.M.C., Karppinen J., Chan D., Fan B., Ho D.W.H., Kao P.Y.P., Song Y., Sham P.C., Cheah K.S.E., Leong J.C.Y. and Luk K.D.K., Age-related changes versus
degenerative disc disease. World Forum for Spine Research, World Forum for
Spine Research - The Intervertebral Disc. |
|
Chu L.W., Li Y., Tang A.Y.B., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., A Novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer' s disease in Chinese, Am J Med Genet B. 2007, 144(8): 1007-13. |
|
Durairajan S.S., Yuan Q.J., Xie L., Chan W.S., Kum W.F., Koo I , Liu C., Song Y., Huang J., Klein W.L. and Li M., Salvianolic acid B inhibits Aβ fibril formation and disaggregates preformed fibrils and protects against Aβ-induced cytotoxicty , Neurochemistry International. 2008, 52: 741-750. |
|
Ho D.W.H., Chan D., Cheung K.M.C., Sham P.C. and Song Y., Family-base linkage and case control association studies, Current Orthopaedics. 2008, 22: 245-250. |
|
Ho D.W.H., Cheung K.M.C., Chan D., Cheah K.S.E., Karppinen J., Sham P.C. and Song Y., LINKAGE ANALYSIS WITH SUBSEQUENT FINE-MAPPING ON FAMILIAL EARLY ONSET-DEGENERATIVE DISC DISEASE, SpineWeek 2008, Geneva, SWITZERLAND. 2008. |
|
Ho D.W.H., Cheung K.M.C., Chan D., Karppinene 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, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
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. World Forum for Spine
Research., The Intervertebral Disc. |
|
Ho D.W.H., Cheung K.M.C., Chan D., Cheah K.S.E., Karppinen J., Sham P.C. and Song Y., Linkage analysis with subsequent fine-mapping on familial early onset-degenerative disc disease., Spine Week 2008, Geneva, May 26-31, 2008. |
|
Huang Q., Li H.Y., Cheung W.M.W., Song Y. and Kung A.W.C., Prediction of osteoporosis candidate genes by computational disease gene identification strategy, 57th Annual Meeting of The American Society of Human Genetics. 2007, 80(suppl): T2119. |
|
Huang Q., Li H.Y., Cheung W.M.W., Song Y. and Kung A.W.C., Prediction of osteoporosis candidate genes by computational disease-gene identification strategy, J Hum Genet. 2008, 53: 644-655. |
|
Kao P.Y.P., Chan D., Cheah K.S.E., Cheung K.M.C., Karppinene J., Yip S.P., Sham P.C. and Song Y., Genome-wide Association Study of Degenerative Disc Disease (DDD) , 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Kao P.Y.P., Chan D., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Cheah K.S.E., Song Y. and Sham P.C., Genome-wide association study of degenerative disc disease (DDD)., Spine Week 2008, Geneva, May 26-31, 2008. . 2008. |
|
Kao
P.Y.P., Chan D., Cheah K.S.E., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Luk K.D.K., Yip S.P., Song Y. and Sham P.C., Genome-wide association study
of degenerative disc disease (DDD)., World Forum for Spine Research - The
Intervertebral Disc. |
|
Lee B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tung L.F., Song Y. and Tanner J.A., Understanding How Polymorphisms in Cerberus-like Result in low Bone Mineral Density, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Li M., Jiang L., Ho S.L., Song Y. and Sham P.C., IGG: A tool to integrate GeneChips for genetic studies. , Bioinformatics. 2007, 23(22): 3105-3107. |
|
Li M., Ho S.L., Sham P.C. and Song Y., In Silico Mapping of a Charcot-marie-tooth Disease Gene in a Pedigree of Hong Kong Chinese, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Ng M.C., Ho J.T., Ho S.L., Lee R., Li G., Cheng T.S., Song Y., Ho W.L., Fong C.Y., Mak W., Chan K.H., Li L.S.W., Luk K.D.K., Hu Y., Ramsden D.B. and Leong Fung L.L.Y., Abnormal diffusion tensor in nonsymptomatic familial amyotrophic lateral sclerosis with a causative superoxide dismutase 1 mutation., J Magn Reson Imaging. . 2008, 27(1): 8-13. |
|
Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Genetic Risk Factors For Intervertebral Disc Degeneration, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia, 28 October - 1 November 2007. |
|
Song
Y., Genetics of Alzheimer disease, The
first Hong Kong and |
|
Song Y., Sham P.C., Cheung K.M.C. and Chan D., Genetics of disc degeneration, Current Orthopaedics. 2008, 22: 259-266. |
|
Song
Y., Chan
D., Kao P.Y.P., Ho D.W.H., Fan B., Karpinen J., Yip S.Y., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Cheung K.M.C., Three genes in the
aggrecan degradation pathway act synergistically to predispose to
degenerative disc disease., World Forum for Spine Research - The
Intervertebral Disc. |
|
Song Y., Three genes in the aggrecan degradation pathway act synergistically to predispose to degenerative disc disease, WORLD FORUM FOR SPINE RESEARCH—THE INTERVERTEBRAL DISC. 2008. |
|
Researcher
: Szeto YY |
|
Project Title: |
Genetic lineage analysis of the Hoxb2-expressing cells in the otocyst |
|
Investigator(s): |
Szeto YY, Sham MH, Cheah KSE |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Small Project Funding |
|
Start Date: |
10/2006 |
|
Abstract: |
|
Homeobox-containing transcription factors
are frequently involved in otic commitment, patterning and other aspects of
inner ear development. Hox genes are well-known for their role in patterning
the embryo along the anteroposterior axis caudal to the midbrain. Moreover,
the pattern they establish in the hindbrain is essential for inner ear
development. In particular, genes of the first paralogous group (Hoxa1 and
Hoxb1) are required for specifying rhombomeres 4 and 5, which in turn affect
inner ear formation (Gavalas et al., 1998). Ectopic expression of Hoxb |
|
List of Research Outputs |
|
Cheah
K.S.E., Szeto Y.Y., Au Y.K., Wynn S., Geng G., Chan Y.S., Chan W.Y., Cheung K.M.C. and Fritzsch B., Context
dependent impact of the Y440X campomelic dysplasia Sox9 mutation, ACGA-HKSMG
International Conference on Genetic and Genomic Medicine, |
|
Cheah
K.S.E., Szeto Y.Y., Au Y.K., Chan Y.S., Lovell-Badge R. and Fritzsch
B., Hearing and balance defects in a mouse model of campomelic dysplasia, Gordon
Research Conference on Craniofacial Morphogenesis and Tissue Regeneration. |
|
Qiu L., Wu X., Chau J.F.L., Szeto Y.Y., Tam W.Y., Guo Z., Chung S.K., Oates P.J., Chung S.S.M. and Yang J.Y., Aldose Reductase Regulates Hepatic Peroxisome Proliferator-activated Receptor {alpha} Phosphorylation and Activity to Impact Lipid Homeostasis., Journal of Biological Chemistry. 2008, 283: 17175-17183. |
|
Szeto
Y.Y., Au
Y.K., Wynn S., Chan Y.S.,
Lovell-Badge R., Chan W.Y., Fritzsch B. and Cheah K.S.E., A mouse model for hearing
and balance defects in campomelic dysplasia, 6th Molecular Biology of
Hearing & Deafness Conference. |
|
Szeto
Y.Y., A mouse model for hearing and balance
defects in campomelic dysplasia, 6th Molecular Biology of Hearing &
Deafness Conference. 11-14 July 07, |
|
Researcher
: Tai CP |
|
List of Research Outputs |
|
Lu L., Li X.T., Tai C.P., Huen M.S.Y., Liu D., Cheah K.S.E. and Huang J., Optimization of single stranded oligonucleotide-mediated modification of plasmid DNA., Biotechniques. 2008, 44: 217-20,222,224. |
|
Researcher
: Tam PKH |
|
Project Title: |
Transgenesis animals as bioreactors: production of a new immunosuppressive protein CTLA4Ig by transgenesis |
|
Investigator(s): |
Tam PKH, |
|
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 |
|
Project Title: |
Establishing a
"train-the-trainers" programme for paediatric surgery in |
|
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 |
|
Investigator(s): |
Tam PKH, Lin CL |
|
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: |
The role of sonic hedgehog in immune system |
|
Investigator(s): |
Tam PKH, Lin CL |
|
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 |
|
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 |
|
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 |
|
Investigator(s): |
Tam PKH, Chan KL, Zhan JH, Jin XQ, Wong KKY |
|
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 |
|
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. |
|
Project Title: |
Molecular basis of biliary atresia |
|
Investigator(s): |
Tam PKH, Garcia-Barcelo MM, Miao X |
|
Department: |
Surgery |
|
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
|
Start Date: |
07/2006 |
|
Abstract: |
|
Objective: To evaluate the human INV,
CFC1, ZIC3, HES, JAGGED1 and NOTCH genes for the presence of coding region
mutations in patients affected with biliary atresia (BA). Problems being
adressed: There is a need to clarify the involvement of these genes in the
defective morphogenesis of the bile-ducts to assess their role in the genetic
network underlying biliary atresia (BA). Therefore, we propose to conduct a
large-scale mutation screening of these genes in BA patients. We will also
perform functional analysis of the mutations found. This study will be
conducted on 150 BA patients of Chinese origin and will be the first study
ever conducted on Chinese at such relatively large scale.Background and key
isuesExtrahepatic Biliary Atresia (BA) is the cause of neonatal cholestasis
(arrest of the normal flow of bile) and defines the inflammatory obliteration
of the extrahepatic biliary system. The incidence of the disease ranges from
approximately |
|
Project Title: |
Study of the genetic basis of biliary atresia |
|
Investigator(s): |
Tam PKH, Garcia-Barcelo MM, Miao X, Sham PC |
|
Department: |
Surgery |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
01/2007 |
|
Abstract: |
|
(1) To conduct a whole-genome case-control association study for genes involved in BA by using GeneChip Mapping 500K Set from Affymetrix and will approximately gather clinical data and DNA from 200 BA patients of Chinese origin; (2) to generate information on: a) the genetic susceptibility to develop BA: b) the genetic predisposition to develop secondary biliary cirrhosis after surgery, thought to be an autoimmune process; c) yet unknown genetic causes that may trigger the disease. |
|
Project Title: |
Whole genome family based association study to search for RET-dependent modifiers in Hirchsprung's disease |
|
Investigator(s): |
Tam PKH, Garcia-Barcelo MM, Miao X, Cherny SS |
|
Department: |
Surgery |
|
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
|
Start Date: |
05/2007 |
|
Abstract: |
|
Hirschsprung's disease (HSCR) is a
congenital disorder in which there is an absence of ganglion cells in
variable portions of the lower digestive tract. Its incidence varies among
populations, being more frequent in Asians. HSCR patients can be classified
according to the severity of the phenotype into long (L-SHCR) and short (S-HSCR)
segment-aganglionosis. HSCR presents mostly sporadically although it can be
familial with a complex pattern of inheritance including low, sex-dependent
penetrance and phenotypic variability. The male:female ratio (M:F) is ≈4:1 among S-HSCR patients and ≈1:1
among L-HSCR patients(1). The RET gene, encoding a tyrosine-kinase receptor
is the major HSCR gene and its expression is crucial for the development of
the enteric ganglia. Reduced penetrance of RET mutations and variable
expression of HSCR phenotype suggest that more than one gene is required.
Current data indicates that S-HSCR manifestation always requires RET (major
gene) and other interacting susceptibility alleles(2). While the pattern of
inheritance of L-HSCR can be more easily explained by combining the nature of
the RET mutations and the effect of a stronger modifier(3), that of S-HSCR is
considerably more complex requiring RET and several other loci, possibly
RET-dependent modifiers(2). HSCR is as an oligogenic entity currently being
genetically dissected and used as a paradigm for the study of
polygenic/complex diseases(2;4). Yet, further insight into the genes
governing S-HSCR in particular is to be gained in order to explain the
transmission of S-HSCR, and other particulars such as gender bias. The basic
premise is that common genetic variants are involved in the manifestation of
the HSCR phenotype which in turn may also depend on the RET mutational type
of the patients. Finding additional HSCR loci requires a large-scale SNP
analyses on a collection of patients with well defined phenotypes/RET
genotypes. The need for such studies has also been raised by the
International HSCR Consortium of which we are not only active participants
but the only source of samples from patients of Chinese origin. Along with
the consortium, we have conducted a Transmission Disequilibrium Test (TDT) as
a family association study on 72 S-HSCR trios using 250.000 SNPs (36 trios
have already been interrogated for the 262,000 SNPs comprised on the array
using Nsp restriction enzyme and the other 36 are currently being done for
the 238,000 SNPs on the Sty array). We believe that increasing the density of
the SNPs of this pilot study (TDT) will provide us with a much more robust
set of data to build on. Therefore, we are proposing to complete the analysis
of the 72 trios with the complete 500K set (each trio to be interrogated for
500,000 SNPs; that is with both SNP arrays). Our data will be compared to
that obtained in a complementary study conducted on the Caucasian consortium
S-HSCR trios. This will help elucidate whether RET modifiers modulating the
phenotype are shared among populations.REFERENCES:1. Amiel J, Lyonnet S 2001
Hirschsprung disease, associated syndromes, and genetics: a review. J Med
Genet 38:729-7392. Gabriel SB, Salomon R, Pelet A, Angrist M, Amiel J,
Fornage M, Attie-Bitach T, Olson JM, Hofstra R, Buys C, Steffann J, Munnich
A, Lyonnet S, Chakravarti A 2002 Segregation at three loci explains familial
and population risk in Hirschsprung disease. Nat Genet 31:89-933. Bolk S,
Pelet A, Hofstra RM, Angrist M, Salomon R, Croaker D, Buys CH, Lyonnet S,
Chakravarti A |
|
List of Research Outputs |
|
Zhang M., Chee D.M.C., Leung C., Tam P.K.H., Lui V.C.H. and Sham M.H., Generation of Mutant Mouse Models for Studying the Role of Sox10 Functional Domains in Enteric Nervous System Development, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Zhou
M., Wang Y., Lam K.S.L., Tam P.K.H., Hoo R.L.C., Liu J. and Xu A., Increased Vulnerability to Liver
Injury is Associated with Decreased Mitochondrial Activities in Adiponectin
Knockout Mice: Potential Roles of UCP |
|
Researcher
: Tang AYB |
|
List of Research Outputs |
|
Chu L.W., Li Y., Tang A.Y.B., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., A Novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer' s disease in Chinese, Am J Med Genet B. 2007, 144(8): 1007-13. |
|
Researcher
: Tang LF |
|
List of Research Outputs |
|
Cheung C.L., Tang L.F., Sham P.C., McClug P., Chan S.Y., Smith D.K., Su A.I., Cheah K.S.E., Kung A.W.C. and Song Y., Genome-wide Haplotype Association Mapping (HAM) in Mice Leads to an Identification of a Genetic Variant in CER1 Associated with Bone Mineral Density in Premenopausal Women, ASBMR 29th Annual Meeting, Honolulu, Hawaii, USA, September 16-19, 2007. |
|
Researcher
: Tang VHM |
|
List of Research Outputs |
|
Tang V.H.M., Siu K.L. and Jin D., Roles of Yeast Peroxiredoxins In Cellular Defence Against DNA Damage, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Tang
V.H.M., Siu
K.L. and Jin D., Roles of yeast
peroxiredoxins in cellular defense against DNA damage., Cold Spring Harbor
Laboratory 2007 meeting on Yeast Cell Biology, |
|
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, 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 PPK |
|
Project Title: |
Targeting sclerostin with aptamer-based inhibitors as an approach to osteoporosis therapy |
|
Investigator(s): |
Tanner JA, Chan D, Cheah KSE |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
11/2006 |
|
Abstract: |
|
(1) Sclerostin purification; (2) Sclerostin functional assay development; (3) artamer selection and evolution; (4) aptamer validation. |
|
Project Title: |
Targeting glutamate synthase for tuberculosis drug development |
|
Investigator(s): |
Tanner JA |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Research Fund for the Control of Infectious Diseases - Mini Grants |
|
Start Date: |
01/2007 |
|
Abstract: |
|
To clone the gene for the glutamate synthase by PCR and ligation into a protein expression vector for heterologous protein expression in E. coli, to express and purify the protein form E. coli, and to characterize the protein by standard enzymology and structural techniques. |
|
List of Research Outputs |
|
Chan C., Leung M.C.M., Chan D., Cheah K.S.E. and Tanner J.A., Identification of Sclerostin Interacting Partners: Steps Towards Osteoporosis Therapy with Aptamer-based Inhibitors, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Periostin interacts with sclerostin and inhibits its antagonistic effect on Wnt signalling, International Bone and Mineral Society (IBMS) Workshop: Bone biology and therapeutics, Davos, Switzerland. 2008. |
|
Chan C.S.L., Leung C.M., Chan D., Cheah K.S.E. and Tanner J.A., Purification and identification of sclerostin interacting partners: steps towards therapy with aptamer-based inhibitors, HKU 12th Research Postgraduate Symposium. 2007. |
|
Chan W.L., Chan D., Lee S., Cheah K.S.E. and Tanner J.A., The Proteomics of Protein Misfolding in Chondrocytes, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Correlating Protein Structure with Disease - Understanding the Mechanism of SEDT, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Lee B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tung L.F., Song Y. and Tanner J.A., Understanding How Polymorphisms in Cerberus-like Result in low Bone Mineral Density, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Shum K.T. and Tanner J.A., In vitro aptamer selection against the SARS Coronavirus Helicase, Annual Symposium of the Hong Kong Proteomics Society. 2007. |
|
Shum K.T., Miller A.D. and Tanner J.A., In vitro aptamer selection against the SARS coronavirus helicase and their intracellular delivery, Oligonucleotide Therapeutics Society Third Annual Meeting, Berlin, Germany. 2007. |
|
Shum K.T. and Tanner J.A., Selection and Delivery of Aptamers Against the SARS Coronavirus Helicase, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Shum K.T. and Tanner J.A., Selection and Delivery of Aptamers against the SARS Coronavirus Helicase, HKU 12th Research Postgraduate Symposium. 2007. |
|
Tanner
J.A., Leung
C.M., Wong L.Y., Miller A.D. and Shum K.T., New Selection and Delivery
Approaches for Nucleic Acid Aptamers against Proteomic Targets, Human
Proteomics Organisation (HUPO) 2007 Meeting, |
|
Yang N., Tanner J.A., Zheng B., He M.L., Lu L., Jiang J.Q., Shum K.T., Lin Y., Wong K.L. and Lin M.C., Bismuth Complexes Inhibit the SARS Coronvirus, Angew. Chem. Int. Ed. 2007, 46: 6464. |
|
Yang N., Tanner J.A., Zheng B., Watt R.M., He M.L., Lu L., Jiang J., Shum K.T., Lin Y., Wong K.L., Lin M.C., Kung H.F., Sun H. and Huang J., Bismuth complexes inhibit the SARS coronavirus, Angewandte Chemie International Edition. 2007, 46: 6464-6468. |
|
Yang N., Tanner J.A., Wang Z., Huang J., Zheng B., Zhu N. and Sun H., Inhibition of SARS coronavirus helicase by bismuth complexes, Chemical Communications. 2007, 4413-4415. |
|
Yang N., Tanner J.A., Huang J., Zheng B. and Sun H., Inhibition of the SARS coronavirus by Bismuth Compounds, 13th International Conference on Biological Inorganic Chemistry (ICBIC-13), Vienna, Austria, July 15-20. 2007. |
|
List of Research Outputs |
|
Chik H.H.Y., Chan W.C.W., Cheng Y.W., Tsang K.Y., Cheah K.S.E. and Chan D., Ectopic Expression Of Unfolded Mutant Collagen X In Bone Cells Results In Generalised Hyperostosis in Mice, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Ressort, Cairns, Australia. 2007. |
|
Researcher
: Tsang SW |
|
List of Research Outputs |
|
Tsang
S.W., Involvement of Pdzd |
|
Tsang S.W., mab-7 encodes a novel transmembrane protein that orchestrates sensory ray morphogenesis in C. elegans , Developmental Biology. 2007, 312: 353-366. |
|
Researcher
: Tsang SW |
|
List of Research Outputs |
|
Tsang
S.W., Involvement of Pdzd |
|
Tsang S.W., mab-7 encodes a novel transmembrane protein that orchestrates sensory ray morphogenesis in C. elegans , Developmental Biology. 2007, 312: 353-366. |
|
Researcher
: Tsui YP |
|
List of Research Outputs |
|
Tsui Y.P., Shea G.K.H., Chan Y.S. and Shum D.K.Y., Preparations of Chitosan Support for Cultures of Schwann Cells and Transdifferentiated Mesenchymal Stem Cells, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Researcher
: Wang J |
|
List of Research Outputs |
|
Wang J. and Huang J., Visualizing the Proteome of Escherichia coli by Labeling E. Coli Chromosomal Genes with Fluorescent Tags, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Wang X |
|
List of Research Outputs |
|
Wang X., Wong E.Y.M., Hui C.C. and Sham M.H., Understanding Hindbrain Neurogenesis by Analysis of a Hoxb3Transgenic Mouse Mutant SL2, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Researcher
: Wang Y |
|
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. |
|
Project Title: |
Role of Mitochondria in Adiponectin-mediated Protective Effects Against Obesity-related Hepatic Steatosis and Steatohepatitis |
|
Investigator(s): |
Wang Y, Xu A |
|
Department: |
Genome Research Centre |
|
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
|
Start Date: |
07/2007 |
|
Abstract: |
|
Non-alcoholic fatty liver disease (NAFLD) is one of the major health concerns closely associated with obesity, which is now reaching an epidemic level worldwide [1]. Recent studies suggest that NAFLD is also the component of the metabolic syndrome, a constellation of several inter-related risk factors for Type 2 Diabetes and cardiovascular diseases [2]. NAFLD is the most frequent hepatic lesion in developed countries, with an estimated prevalence of 10-25% [3]. The presence of steatosis in liver is an important risk factor for the development of additional liver injuries, such as non-alcoholic steatohepatitis (NASH), viral hepatitis, drug-induced hepatotoxicity and alcoholic steatohepatitis (ASH) etc [4]. About 5 % of hepatic steatosis will progress to significant fibrosis and cirrhosis and over 80 % of these cases will further develop liver cancer [1]. Adiponectin is an important adipokine abundantly produced from adipose tissues [5]. This adipokine has recently attracted great attention due to its anti-diabetic and anti-atherogenic activitities [6]. Circulating concentrations of adiponectin are decreased in obesity and its related pathologies, including insulin resisatnce, type 2 diabetes and cardiovascular diseases [6]. Supplementation with recombinant adiponectin could improve insulin sensitivity, decrease blood glucose levels, reverse atherogenic dyslipidemia and alleviate atherosclerosis in various animal models [5]. A previous study from our group provided the first evidence demonstrating that adiponectin possesses potent protective effects against both alcoholic and nonalcoholic fatty liver disease and steatohepatitis [7]. In both ethanol-fed mice and ob/ob obese mice, chronic treatment with recombinant adiponectin markedly attenuated hepatomegaly and steatosis, and also significantly decreased the hepatic inflammation loci and serum alanine aminotransferase (ALT), an established marker of liver injury [7]. More recently, we demonstrated that adiponectin treatment could also attenaute liver injury and fibrosis induced by pharmacological compounds and bile duct ligations [8]. Consistent with our data, several other group has recently confirmed the hepato-protective effects in different animal models with liver injury, such as carbon tetrachloride-treated mice with fibrosis and lipopolysaccharide (LPS)/D-galactosamine-treated mice with steatosis and inflammation [9-11]. These animal data were also supported by our clinical observations showing an inverse association between serum levels of adiponectin and ALT in Chinese obese subjects [7]. Moreover, plasma adiponectin levels are significantly lower in patients with NAFLD compared to the sex and age matched healthy controls [12, 13]. NASH patients with lower levels of adiponectin show higher grades of inflammation [14]. In addition, decreased plasma adiponectin concentrations are closely related to steatosis in hepatitis C virus-infected patients [15]. Taken together, these clinical and animal data suggest that low plasma levels of adiponectin might be an important risk factor for the development of fatty liver, steatohepatatis and other forms of liver injury. Adiponectin and its agonists might represent an effective strategy for treatment and prevention of these diseases. Nevertheless, the molecular and cellular mechanisms underlying the hepato-protective effects of adiponectin remain largely elusive so far. It is now known that mitochondrial dysfunction plays a central role in various forms of hepatic steatosis and liver injury [16-18]. Mitochondria are involved in fatty acid β-oxidation, tricarboxylic acid cycle (TCA) and oxidative phosphorylation. In patients with NASH, the hepatic mitochondria exhibit ultrastructural lesions and decreased activity of respiratory chain complexes [19, 20]. In this condition, the decreased activity of the respiratory chain results in accumulation of reactive oxygen species (ROS), and oxidization of fat deposits to form lipid peroxidation products, which in turn , may cause the diverse lesions of steatohepatitis, necrosis, inflammation, and fibrosis [21, 22]. The increased mitochondrial ROS formation in steatohepatitis could directly damage mitochondria DNA (mtDNA) and respiratory chain polypeptides, which further block the flow of electrons within the respiratory chain [20, 23]. Moreover, ROS cause NF-κB activation and induce the hepatic synthesis of tumor necrosis factor-α (TNF α), which triggers mitochondria membrane permeability and apoptosis [24]. Impaired mitochondrial integrity and transcriptional capacity have also been observed in LPS- and retrovirus-mediated hepatic injury [25, 26]. Taken together, these evidences suggest that mitochondria dysfunction might play a key role in the pathogenesis of NAFLD, NASH and other forms of liver injuries. In this study, we will test our hypothesis that adiponectin exerts its hepato-protective effects partly through promoting mitochondrial biogenesis and allevaiting mitochondria dysfunctions. The specific objectives are: 1. To investigate whether the accelerated liver injury is associated with impaired mitochondria dysfunction in adiponectin knockout mice; 2. To test whether adenovirus-mediated overexpression of adiponectin stimulates mitochondria biogenesis and reverses mitochondria dysfunction associated with obese mice. 3. To elucidate the potential signalling pathways involved in adiponectin-mediated modulation of mitochondria functions in liver. |
|
List of Research Outputs |
|
Zhou
M., Wang Y., Lam K.S.L., Tam P.K.H., Hoo R.L.C., Liu J. and Xu A., Increased Vulnerability to Liver
Injury is Associated with Decreased Mitochondrial Activities in Adiponectin
Knockout Mice: Potential Roles of UCP |
|
Researcher
: Wang Z |
|
List of Research Outputs |
|
Wang Z., Zhou Z., Liu D. and Huang J., Characterization of single-stranded oligonucleotide-mediated deletion in >mammalian cells., Oligonucleotides. 2008, 18(1): 21-32. |
|
Wang Z., Zhang X., Zhu G. and Huang J., Kif5b is Responsible for Muscle Development and Normal Function, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Yang N., Tanner J.A., Wang Z., Huang J., Zheng B., Zhu N. and Sun H., Inhibition of SARS coronavirus helicase by bismuth complexes, Chemical Communications. 2007, 4413-4415. |
|
Researcher
: Wang Z |
|
List of Research Outputs |
|
Wang Z., Zhou Z., Liu D. and Huang J., Characterization of single-stranded oligonucleotide-mediated deletion in >mammalian cells., Oligonucleotides. 2008, 18(1): 21-32. |
|
Wang Z., Zhang X., Zhu G. and Huang J., Kif5b is Responsible for Muscle Development and Normal Function, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Yang N., Tanner J.A., Wang Z., Huang J., Zheng B., Zhu N. and Sun H., Inhibition of SARS coronavirus helicase by bismuth complexes, Chemical Communications. 2007, 4413-4415. |
|
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. |
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Project Title: |
The identification and characterization of new bacterial protein targets for inhibition - determining their potential for antibiotic development |
|
Investigator(s): |
Watt RM |
|
Department: |
Chemistry |
|
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
|
Start Date: |
08/2006 |
|
Abstract: |
|
As a newly appointed RAP within the
chemistry department, I would like to establish a new area of research
focused on the study of essential bacterial proteins, with a view to
discovering new antibiotic compounds, and new targets for antibacterial
chemotherapy. There are two main research objectives in this Seed Funding
proposal: 1) To biochemically characterize several putatively essential
bacterial proteins, and identify at least two that will be amenable to
subsequent high throughput inhibitor screening 2) To purify the ‘native’
complexes formed by a number of these essential proteins within their natural
host using a newly developed ‘tandem affinity’ (TAP) tag procedure, for
subsequent analysis by mass spectrometry After reviewing the literature, and
performing various bioinformatic analyses of sequenced bacterial genomes, a
number of candidate proteins have been identified for detailed investigation
(see below). These proteins are all essential or putatively essential, and
fall within three specific functional categories. I have focused on proteins
from a variety of bacterial species that are either model organisms, or are
medically important pathogens. This will enable the functions of different
family members (homologues) to be compared and contrasted, hopefully allowing
some important general conclusions to be drawn after the completion of the
experiments. The 3 areas I will focus on are: Polyphosphate and pyrophosphate
degradation A small family of GTPases of poorly defined or unknown function
The last two steps of the methylerythriyol phosphate (MEP) biosynthetic
pathway All organisms have at least one inorganic pyrophosphatase, which
catalyzes the breakdown of pyrophosphate (diphosphate) to two phosphate
(orthophosphate) molecules. The very high free energy for this process is the
driving force for many thermodynamically unfavourable biochemical reactions.
Consequently, the activity of this enzyme activity is essential in all known
organisms. Certain bacteria appear to have two types of pyrophosphatase: one
that preferentially uses magnesium as a cofactor (type A, Ppa), and another
that prefers manganese or cobalt (Family II, or type C, PpaC). Mutagenesis
studies in a number of organisms have shown that both genes are essential,
which suggests that the two proteins have non-overlapping or
non-complementary functions. The PpaC family of pyrophosphatases may also
play a role in the degradation of polyphosphate (long chain phosphate), which
is an enigmatic intracellular molecule, with a poorly defined function. Polyphosphate
is thought to be involved in metal transport, metal sequestration and the
stress response, amongst many other processes. I have identified a putative
type C pyrophosphatase in Mycobacterium tuberculosis (the causative agent of
tuberculosis), as well as another gene that may encode an additional
exopolyphosphatase (which degrades polyphosphate) or possibly even a
guanosine tetraphosphatase (ppGpp) hydrolase (a protein that degrades an
important nucleotide-phosphate signaling molecule). Consequently, I will
clone, express and characterize the biochemical and biophysical properties of
these two proteins, to investigate this hypothesis. Furthermore, as both
genes are essential, I will determine whether it will be possible to develop
biochemical assays that will be suitable for use in high throughput
inhibition studies (with a commercial library of compounds, to be performed
at a later date). Finding specific inhibitors for these two classes of
bacterial enzymes is especially attractive, as there are no homologues in
higher organisms. Within bacteria, there is a family of essential and highly
conserved bacterial GTPase proteins, whose activities are currently poorly
understood. The family comprises the following genes: era (bex), engA (der,
yfgK), engB (yihA), engD (obg, yhcf), trmE (thdF), hflX, ftsY, obgE (ctgA,
yhbZ), and ffh. However, there may be redundancy or some overlapping of
activities within this family, as some bacteria do not appear to have all of
them (they generally have between 5 to 8 members). I have already cloned a
number of these genes from Pseudomonas aeruginosa and Staphylococcus aureus
(opportunistic pathogens), vibrio cholerae (the causative agent of cholera)
and E. coli (a model bacterium, that is sometimes pathogenic). For this proposal,
I plan to investigate their NTPase (nucleotide and deoxynucleotide
triphosphatase) activities, specifically regarding its stimulation upon RNA
or DNA binding. I will also try to identify interacting protein species
within the cell, using a TAP tag. If the NTPase activity is high enough, then
it may be possible to design assays amenable to high throughput inhibitor
screening. Until recently, it was thought that all organisms synthesized
isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), key
metabolites in isoprenoid biosynthesis, via the same route: the mevalonate
pathway. However, less than 10 years ago, several researchers showed that in
most bacteria, some parasites, and in the chloroplasts of plants, that this
was not the case. Subsequently the 7-step methylerythritol phosphate (MEP)
pathway was gradually elucidated. As the synthesis of IPP and DMAPP is
essential in all organisms, this makes the MEP pathway an excellent target
for the development of selective antibiotic, anti-parasitic or herbicidal
agents. The first 5 steps of the MEP pathway are well understood, but the
mechanisms of the last two steps, catalyzed by the GcpE and LytB proteins
respectively, remain to be fully established. Both of these enzymes require
auxiliary redox proteins for activity. Working in collaboration with a
research team in |
|
Project Title: |
Isoprenoid biosynthesis via the methylerythritoal phosphate (MEP) pathway: proteomic analysis and identification of targets for inhibition |
|
Investigator(s): |
Watt RM |
|
Department: |
Chemistry |
|
Source(s) of Funding: |
France/Hong Kong Joint Research Scheme - Travel Grants |
|
Start Date: |
01/2007 |
|
Abstract: |
|
1. Identify the protein complexes (specifically, the accessory redox proteins) that are involved in the final two steps of the essential methylerythritol phosphate (MEP) biosynthetic pathway in a number of plant and medically-important bacterial species. 2. Compare and contrast experimental results with literature data. Thoroughly investigate any potential differences that may exist in the nature of the putative accessary protein complexes used in the various plant and bacterial species (i.e. are there different mechanisms for protein reduction/oxidation?). 3.Evaluate overall project findings, and formulate strategies for future research directions. Identify candidate proteins as possible targets for inhibition, with a view to the development of potential biocide (antibacterial, herbicide) agents. |
|
Researcher
: Wong EYM |
|
List of Research Outputs |
|
Wang X., Wong E.Y.M., Hui C.C. and Sham M.H., Understanding Hindbrain Neurogenesis by Analysis of a Hoxb3Transgenic Mouse Mutant SL2, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Wong E.Y.M., Fellowship was presented by the 6th Molecular Biology of Hearing and Deafness Conference 2007 , Welcome Trust. 2007. |
|
Wong
E.Y.M., Sae-Pang
J.J., Mak S.S., Ling K.W., Chan W.Y.,
Chung S.K., Cheah K.S.E. and Sham M.H., Gain-of-function Hoxb3
mutation affects endothelin-1 pathway in craniofacial development., Gordon
Research Conference on Craniofacial Morphogenesis & Tissue Regeneration, |
|
Wong E.Y.M., Small project fund and Top-up fund for supporting the project related to the analysis of the Hoxb1 - Six1 regulatory pathway essential for sensory neurogenesis of the inner ear, The Committee on Research and Conference Grants in the University of Hong Kong . 2007. |
|
Wong
E.Y.M., The University of Hong Kong/China
Medical Board Grant for supporting the overseas training in the Professor
Bernd Fritzsch in the |
|
Wong
E.Y.M., Chan
Y.S., Cheah K.S.E. and Sham M.H., The role of Hox genes in
dorsoventral patterning and morphogenesis of inner ear. , Gordon Research
Conference on Auditory System in |
|
Wong
E.Y.M., chan Y.S., Wu D.K. and Cheah K.S.E., The role of Hox genes in
mouse inner ear development, 6th Molecular Biology of Hearing &
Deafness Conference. 11-14 July 07, |
|
Wong
E.Y.M., Chan
Y.S., Cheah K.S.E. and Sham M.H., The role of Hox genes in otic
vesicle patterning in Six1 regulatory pathway. , Gordon Research
Conference on Auditory System (Graduate Research Seminar) in |
|
Wong
E.Y.M., Chan Y.S., Wu D., Cheah K.S.E. and Sham M.H., The role of HOX genes
in mouse inner ear development., The 6thMolecular Biology of Hearing and
Deafness Conference, |
|
Researcher
: Wong LY |
|
List of Research Outputs |
|
Tanner
J.A., Leung C.M., Wong L.Y., Miller A.D. and Shum K.T., New Selection and Delivery
Approaches for Nucleic Acid Aptamers against Proteomic Targets, Human
Proteomics Organisation (HUPO) 2007 Meeting, |
|
Project Title: |
Kappa-opioid receptor mediated cellular stress response: the role of Inositol 1,4,5-trisphosphate and diacylglycerol |
|
Investigator(s): |
|
|
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): |
|
|
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): |
|
|
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): |
|
|
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. |
|
Project Title: |
Redox-mediated posttranscriptional regulation of CHOP expression: its implication in CHOP-mediated pathologies |
|
Investigator(s): |
|
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
01/2007 |
|
Abstract: |
|
(1) Characterization of the 625-688 (-60bp) region and the ARE; (2) regulation of CHOP mRNA stability by known RNA-binding protein; (3) identification of trans-acting RNA binding proteins. |
|
List of Research Outputs |
|
Lai W.L. and Wong N.S., The PERK/eIF2α signaling pathway of Unfolded Protein Response is essential for N-(4-hydroxyphenyl) retinamide (4HPR)-induced cytotoxicity in cancer cells, Exp Cell Res. 2008, 314(8) pp: 1667-1682. |
|
Wong
N.S. and Lai
W.L., The role of reactive oxygen species in UPR-mediated cell death, "Cancer
therapeutics: the road ahead" A |
|
Researcher
: Wong SYY |
|
List of Research Outputs |
|
Kwong
W.H., Wong S.Y.Y., Kao P.Y.P., Fritzsch B. and Cheah K.S.E., An essential role for type
IIA procollagen in mouse inner ear development, 6th Molecular Biology of
Hearing & Deafness Conference. 11-14 July 07, |
|
Researcher
: Wynn SL |
|
List of Research Outputs |
|
Cheah
K.S.E., Leong V.Y.L., Gao B., Dung W.F., Leung K.K.H., Wynn S.L., Lau J.Y.B., Niewiadomska A.K., Melhado I.G. and Chan D., Dual roles of Sox |
|
Project Title: |
Investigating
the functional involvement of PDZD |
|
Investigator(s): |
|
|
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: |
Activation of FOXM1 by the Raf/MEK/MAK pathway and regulation of cell cycle progression at the G2/M phase |
|
Investigator(s): |
|
|
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): |
|
|
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 E |
|
List of Research Outputs |
|
Li
S.K.M., Smith D.K., Leung G.W.Y., Cheung M.S., Lam E.W., Dimri G.P. and Yao K.M., FoxM |
|
Suen P.M., Zou C., Zhang Y.A., Lau T.K., Chan J., Yao K.M. and Leung P.S., PDZ-domain containing-2 (PDZD2) is a novel factor that affects the growth and differentiation of human fetal pancreatic progenitor cells, The International Journal of Biochemistry and Cell Biology. 2008, 40: 789-803. |
|
Tam C.W., Liu V.W.S., Leung W.Y., Yao K.M. and Shiu S.Y.W., The autocrine sPDZD2 protein is a potential p53 activator, AACR Centennial Conference on Translational Cancer Medicine: Technologies to Treatment. 2007, B40. |
|
Wong H.L., Wang M., Cheung P.T., Yao K.M. and Chan B.P., A 3D collagen microsphere culture system for GDNF-secreting HEK293 cells with enhanced protein productivity, Biomaterials. Elsevier Ltd., 2007, 28: 5369-5380. |
|
Researcher
: Yau TO |
|
Project Title: |
The role of Frizzled-7, receptor of the WNT/β-catenin signalling pathway, in hepatocellular carcinoma: Implications in tumorigenesis and metastasis |
|
Investigator(s): |
Yau TO, Ng IOL |
|
Department: |
Pathology |
|
Source(s) of Funding: |
Small Project Funding |
|
Start Date: |
10/2006 |
|
Abstract: |
|
Hepatocellular carcinoma (HCC) is second
commonest in Asia and in |
|
Researcher
: Yee AFY |
|
List of Research Outputs |
|
Song Y., Cheung K.M.C., Ho D.W.H., Poon S.C.S., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F.Y., Leong J.C.Y., Luk K.D.K., Yip S., Karppinen J., Cheah K.S.E., Sham P.C., Ikegawa S. and Chan D., Genetic Risk Factors For Intervertebral Disc Degeneration, 7th Pan Pacific Connective Tissue Societies Symposium 2007 - Shangri-La Resort, Cairns, Australia, 28 October - 1 November 2007. |
|
Yee A.F.Y., Protein and Gene Expression Profiles of the Intervertebral Disc, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Yee
A.F.Y., Melhado
I.G., Cheah K.S.E., Cheung K.M.C. and Chan D., Protein expression of the
intervertebral disc: in Health and disease., World Forum for Spine
Research - The Intervertebral Disc. |
|
Yee
A.F.Y., Melhado
I.G., Cheah K.S.E., Chan D. and Cheung K.M.C., Use of tandem mass
spectrometry as a tool for proteomics studies in aging and degeneration
processes of the intervertebral disc., Spine Week 2008, |
|
Researcher
: Yuan QJ |
|
List of Research Outputs |
|
Durairajan S.S., Yuan Q.J., Xie L., Chan W.S., Kum W.F., Koo I , Liu C., Song Y., Huang J., Klein W.L. and Li M., Salvianolic acid B inhibits Aβ fibril formation and disaggregates preformed fibrils and protects against Aβ-induced cytotoxicty , Neurochemistry International. 2008, 52: 741-750. |
|
Researcher
: Zhang JCL |
|
List of Research Outputs |
|
Chan W.C.W., Zhang J.C.L., Dung W.F., Wong Q., Parmacek M.S., Lau C.P. and Cheah K.S.E., Functional analysis of SM22β by targeted gene deletion in mice. , ACGA-HKSMG International Conference on Genetic and Genomic Medicine, Hong Kong. June 8-11, 2008. . 2008. |
|
Chan
W.C.W., Zhang J.C.L., Dung W.F., Wong Q., Parmacek M.S., Lau C.P. and Cheah K.S.E., Functional analysis of
SM22β by targeted gene deletion in mice., ACGA-HKSMG International
Conference on Genetic and Genomic Medicine, |
|
Researcher
: Zhang L |
|
List of Research Outputs |
|
Zhang L., Krishnan V. and Zhou Z., Prelamin A compromises DNA Damage-induced Chromatin Relaxation to Promote Genomic Instability and Aging, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Zhang M |
|
List of Research Outputs |
|
Zhang M., Chee D.M.C., Leung C., Tam P.K.H., Lui V.C.H. and Sham M.H., Generation of Mutant Mouse Models for Studying the Role of Sox10 Functional Domains in Enteric Nervous System Development, 12th Research Postgraduate Symposium, December 12 & 14, 2007. |
|
Researcher
: Zhang X |
|
List of Research Outputs |
|
Wang Z., Zhang X., Zhu G. and Huang J., Kif5b is Responsible for Muscle Development and Normal Function, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
|
Researcher
: Zhang Y |
|
List of Research Outputs |
|
Zhang
Y., Liu
J., Chan Y.S. and Shum D.K.Y., Heparanase expression in
Schwann cells as revealed in injured sciatic nerves and dorsal root ganglion
explant culture, . Seventh IBRO World Congress of Neuroscience, |
|
Zhang Y., Chau C.H., Lai C.H., Chan Y.S. and Shum D.K.Y., Heparanase upregulation in
astrocytes and macrophages recruited to the injured spinal cord. Neuroscience
Research 58: S145, 30th Annual Meeting of |
|
Zhang Y., Studies of heparanase (HPA) gene expression, cellular localization and functions in neural tissues of the rat, PhD. 2007. |
|
Researcher
: Zhang Y |
|
List of Research Outputs |
|
Zhang
Y., Liu
J., Chan Y.S. and Shum D.K.Y., Heparanase expression in
Schwann cells as revealed in injured sciatic nerves and dorsal root ganglion
explant culture, . Seventh IBRO World Congress of Neuroscience, |
|
Zhang Y., Chau C.H., Lai C.H., Chan Y.S. and Shum D.K.Y., Heparanase upregulation in
astrocytes and macrophages recruited to the injured spinal cord. Neuroscience
Research 58: S145, 30th Annual Meeting of |
|
Zhang Y., Studies of heparanase (HPA) gene expression, cellular localization and functions in neural tissues of the rat, PhD. 2007. |
|
Researcher
: Zhou M |
|
List of Research Outputs |
|
Zhou
M., Wang
Y., Lam K.S.L., Tam P.K.H., Hoo R.L.C., Liu J. and Xu A., Increased Vulnerability to Liver
Injury is Associated with Decreased Mitochondrial Activities in Adiponectin
Knockout Mice: Potential Roles of UCP |
|
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: |
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. |
|
Project Title: |
Triggering senescence in tumor cells via unprocessed lamin A |
|
Investigator(s): |
Zhou Z, Wong WT, Kao RYT |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
09/2006 |
|
Abstract: |
|
To investigate whether FTI treatment causes senescence, genomic instability and/or DNA repair defects in tumor cells; to assess the contribution of unprocessed prelamin A to the inhibitory effect of FTIs on tumor growth; to examine whether FTIs can directly inhibit Zmpste24 activity. |
|
Project Title: |
Role of MT1-MMP in wound healing and tumorigenesis |
|
Investigator(s): |
Zhou Z |
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Department: |
Biochemistry |
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Source(s) of Funding: |
Germany/Hong Kong Joint Research Scheme |
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Start Date: |
01/2007 |
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Abstract: |
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1. Understand functions of MT1-MMP in wound healing process 2. Investigate how MT1-MMP affects tumorigenesis, angiogenesis and metastasis |
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List of Research Outputs |
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Jin G., Chan J.K.M. and Zhou Z., Genetic approach to Study the Role of MT1-MMP in Tumor Development in Vivo, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Kandert S., Luke Y., Kleinhenz T.,
Neumann S., Lu W., Jaeger W.M., Munck M., Wehnert M., Muller C.R., Zhou Z. and Noegel A.A., Nesprin-2
giant safeguards nuclear envelope architecture in LMNA S |
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Kong C.T. and Zhou Z., Defective Self-renewal And Early Cellular Senescence In Premature Aging Mesenchymal Stem Cells, Keystone Symposium - Tumor Suppressors And Stem Cell Biology, 24 - 29 February, Vancouver, British Columbia, Canada. 2008. |
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Krishnan V., Liu B. and Zhou Z., Proficiency of DNA repair networks in stem cells as determinants of aging, Cell Science. 2007, Epub. |
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Li J., Wu Y., Wu E.X., Chan D., Cheah K.S.E. and Zhou Z., Accelerated Senescence in Degenerate Intervertebral Disc of Laminopathy-based Premature Aging Mouse Model, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Liu B. and Zhou Z., Lamin A/C, laminopathies and premature ageing, Histology and Histopathology. 2008, 23(6): 747-763. |
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Wang Z., Zhou Z., Liu D. and Huang J., Characterization of single-stranded oligonucleotide-mediated deletion in >mammalian cells., Oligonucleotides. 2008, 18(1): 21-32. |
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Zhang L., Krishnan V. and Zhou Z., Prelamin A compromises DNA Damage-induced Chromatin Relaxation to Promote Genomic Instability and Aging, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Zhou
Z., Epigenetic control of DNA repair in
premature ageing. , The 4th Key Symposium on The Biology of Ageing. . |
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Zhou
Z., Histone modifications in aging and accelerated
aging, East-West Alliance Symposium, |
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Zhou
Z., ISMB NOMINATED SPEAKER: MT1-MMP regulates
FGFR signalling in development, 7th Pan Pacific Connective Tissue
Societies Symposium 2007, Cains, |
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Zhou
Z., KEYNOTE SPEAKER: Understanding Molecular
Mechanism of Laminopathy-based Premature Ageing, Chinese Society of Cell
Biology. |
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Zhou
Z., PLENARY LECTURE: MT1-MMP regulates FGFR
signalling in development, XIIIth International Symposium on Basement
Membranes. |
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Zhou
Z., Prelamin A regulates DNA repair through
histone modifications. , Symposium for the Asia/Oceania Regional Congress
of Gerontology and Geriatrics. . |
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Researcher
: Zhu G |
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List of Research Outputs |
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Wang Z., Zhang X., Zhu G. and Huang J., Kif5b is Responsible for Muscle Development and Normal Function, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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Zhu G., Chan D., Cheah K.S.E. and Huang J., KIF5b is Essential for Growth Plate Organization and Cytokinesis, 12th Research Postgraduate Symposium, December 12 & 14, 2007 . 2007. |
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