DEPT OF BIOCHEMISTRY
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Researcher
: Cai K |
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List of Research Outputs |
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Cai K., Gene Therapy for Lung Cancer by Adeno-associated Virus-mediated Expression of Angiogenesis Inhibitors in Mouse Models., PhD. Thesis. 2006. |
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Cai K., Tse L...Y., Li H., Xu R. and Sham M.H., Vasostatin gene therapy suppressed lung tumor growth and metastasis using adeno-associated virus pseudotype 5 vector, MGH-HKU-Nature China Forum, Hong Kong. March 2007. |
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Researcher
: Chan C |
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List of Research Outputs |
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Liu H., Liu J., Chan C., Chau C.H., Chan Y.S. and Shum D.K.Y., Chondroitin sulfate moieties that are upregulated in Schwann cell-astrocyte encounters, Gordon research Conference on Proteoglycans July 9-14 Andover, New Hampshire, USA. 2006. |
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Researcher
: Chan CH |
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List of Research Outputs |
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Chan
C.H., Ip
M.S.M. and Shum D.K.Y., Targeting
heparan sulfate/syndecan |
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Researcher
: Chan CP |
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List of Research Outputs |
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Chan C.P., Siu K.L., Chin K.T., Yuen K.Y., Zheng B. and Jin D., Modulation of the unfolded protein response by severe acute respiratory syndrome coronavirus spike protein., Journal of Virology. 2006, 80: 9279-9287. |
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Sham M.H., Cheng M.H., Chao Z., Tsang S.L., Chan C.P., Choy R...K...W. and Song Y., Mapping the locus for a novel cataract mouse mutant with microphthalmia and closed eyelid., HUGO 12th Human Genome Meeting, Montreal, Canada. May, 2007. |
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Researcher
: Chan CP |
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List of Research Outputs |
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Chan C.P., Siu K.L., Chin K.T., Yuen K.Y., Zheng B. and Jin D., Modulation of the unfolded protein response by severe acute respiratory syndrome coronavirus spike protein., Journal of Virology. 2006, 80: 9279-9287. |
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Sham M.H., Cheng M.H., Chao Z., Tsang S.L., Chan C.P., Choy R...K...W. and Song Y., Mapping the locus for a novel cataract mouse mutant with microphthalmia and closed eyelid., HUGO 12th Human Genome Meeting, Montreal, Canada. May, 2007. |
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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., Wong L.Y., Chan D., Cheah K.S.E. and Tanner J.A., Purification and Identification of Sclerostin Interacting Partners: Steps towards Osteoporosis Therapy with Aptamer-based Inhibitors, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU . 2006. |
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Lee
B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tang L.F., Song Y. and Tanner J.A., Functional Study of
Cerberus-like and Noggin Proteins: toward a Biochemical Understanding of BMP
Antagonists in Skeletal Disorders, 11th Research Postgraduate Symposium, 7
Dec. 2006. The |
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Shum
K.T., Leung C.M., Wong L.Y., Chan C.S.L. and Tanner J.A., New Approaches for
Therapeutic Aptamer Selection and Delivery, MGH-HKU-Nature |
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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: |
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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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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List of Research Outputs |
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Abbah S.A., Lu W.W., Chan D., Cheung K.M.C., Liu W., Zhao F., Li Z., Leong J.C.Y. and Luk K.D.K., In vitro evaluation of alginate encapsulated adipose-tissue stromal cells for use as injectable bone graft substitute., Biochem Biophys Res Commun. 2006, 347(1): 185-91. |
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Aladin
K.D.M., Lu W.W., Cheung K.M.C., Ngan A.H.W., Chan D. and Luk K.D.K., " Nano Biomechanics Of
Type Ii Collagens In Human Intervertebral Discs", Best Paper Award;
Conference on Biomedical Engineering, BME 2006. |
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Aladin
Kaderbatcha D.M., Lu W.W., Chan D., Yee A.F.Y., Jim J.J.T., Luk K.D.K. and Cheung K.M.C., EXPRESSION OF THE TRP2
ALLELE OF COL |
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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., Nano Structure and
Biomechanics of Human Intervertebral Disc Collagens, International Society
for the Study of the Lumbar Spine. 34th annual Meeting, June 10-14, |
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Chan B.P., Cheung K.M.C., Chan G.C.F., Chan D. and Hui T.Y., Bioengineered intervertebral disc and Methods for Their Preparation., US Regular Patent Application No. 11/742,040 (filed on 30 April 2007). 2007. |
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Chan B.P., Chan G.C.F., Wong H.L., Cheung P.T., Cheah K.S.E. and Chan D., Cell-Matrix Microsphere, Associated Products, Methods for Preparation and Applications., US Regular Patent Application No. 11/750,863 (filed on 18 May 2007).. 2007. |
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Chan C.S.L., Leung C.M., Wong L.Y., Chan D., Cheah K.S.E. and Tanner J.A., Purification and Identification of Sclerostin Interacting Partners: Steps towards Osteoporosis Therapy with Aptamer-based Inhibitors, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU . 2006. |
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Chan
C.W., Gantenbein B., Chan D.,
Lu W., Cheung K.M.C., Lezuo P. and Ito K., Fate
of Mesenchymal Stem Cells Injected Into Intervertebral Discs, International
Society for the Study of the Lumbar Spine. 34th Annual Meeting. |
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Chan D., Gao B., Hu J., Law S.K.F., He L. and Cheah K.S.E., Abnormal IHH signaling affects distal digit patterning in a mouse model with brachydactyly type A1, FECTS XXth & ISMB meeting July 1-5, Oulu, Finland . 2006. |
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Chan D., Song Y., Sham P.C. and Cheung K.M.C., Genetics of disc degeneration, Eur Spine J. 2006, 15 Suppl 15: 317-25. |
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Chan D., Model Systems for Intervertebral Disc regeneration., HKU-University of Toronto Research Meeting, 14-15 Dec,2006. |
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Chan
J.K.M., Chan D. and Zhou Z., Functional Role of MT1-MMP in
FGF Signaling., 11th Research Postgraduate Symposium, 7 Dec. 2006. The |
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Chan W.C.W., Ng V.C.W., Wang C., Tsang K.Y., Cheah K.S.E. and Chan D., ER-stress signaling in the pathogenesis of Schmid metaphyseal chondrodysplasia , Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 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.,
11th Research Postgraduate Symposium, 7 Dec. 2006. The |
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Chan W.L., Chan D., Lee S., Cheah K.S.E. and Tanner J.A., A Proteomic Approach To Study The Molecular Mechanisms Of The Unfolded Protein Response In The Endoplasmic Reticulum Of Chondrocytes, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU . 2006. |
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Chan
Y.L., Yeung K.W.K., Lu W.W., Ngan A.H.W., Luk K.D.K., Chan D., Wu S.L., Liu X.M., |
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Cheung K.M.C., Chan D., Karppinen J., Chen Y.Q., Jim J.J.T., Yip S.P., Ott J., Wong K.K., Sham P.C., Luk K.D.K., Cheah K.S.E., Leong J.C.Y. and Song Y., Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population, Spine. 2006, 31(10): 1143-1148. |
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Cheung K.M.C., Luk K.D.K., Ho D.W.H., Chan D., Cheah K.S.E. and Song Y., Linkage analysis on familial early-onset degenerative disc disease. , Best Poster Award. 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong.. 2007. |
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Cheung
K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S...P., Cheong
J...C...Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan
degradation pathway act synergistically to predispose to degenerative disc
disease., International Society for the Study of the Lumbar Spine. 34th
annual Meeting, June 10-14, 2007 |
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Cheung K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S.P., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan degraduation pathway act synergistically to predispose to degenerative disc disease, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 2007. |
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Chik
H.H.Y., Tsang K.Y., Cheng Y.W., Chan W.C.W., Cheah K.S.E. and Chan D., Genomic Analysis of
Increased Osteoblast Activity in a Mouse with generalized Hyperostosis., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
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Choi
M.Y., Chan C.C.Y., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Molecular Mechanism of
Disease for Spondyloepiphyseal Dysplasia Tarda-Effect of Mutations on sedlin
structure and Function., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
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Guo
X., Irwin M.G., Chan D., Tipoe G.L. and Cheung K.M.C., The Role of
Cyclooxygenase 1 and |
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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 (DDD)., ABS#apbc056 Jan14-17. 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, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 2007. |
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Ho M...S., Tsang K.Y., Lo R.L.K., Susic M., Makitie O., Chan
T...W., Ng V.C.W., Sillence D...O.,
Boot-Handford R...P., Gibson G., Cheung K...M., Cole W...G., Cheah K.S.E. and Chan D., COL |
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Huang J., Zhu G., Cheah K.S.E. and Chan D., KIF5b is essential for growth plate organization, cytokinesis and chondrocytes differentiation., Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 2007. |
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Hui
T.Y., Chan D., Cheung K.M.C., Chan G.C.F., Cheung W.L. and Chan B.P., Chondrogenic differentiation
of human mesenchymal stem cells in three-dimensional
collagen/chondroitin-6-sulfate gels: Influences of cell seeding density and
collagen concentration, International Society for Stem Cell Research 5th
Annual Meeting. Jun 15-21 2007. |
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Kao
P.Y.P., Sham P.C., Chan D., Cheung K.M.C. and Song Y., Investigating Epistasis in
Degenerative Disc Disease., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
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Kao P.Y.P., Chan D., Cheung K.M.C., Cheah K.S.E., Sham P.C. and Song Y., Investigating Epistasis in Degenerative Disc Disease., ABS#apbc101 Jan 14-17, 2007. |
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Lee
B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tang L.F., Song Y. and Tanner J.A., Functional Study of
Cerberus-like and Noggin Proteins: toward a Biochemical Understanding of BMP
Antagonists in Skeletal Disorders, 11th Research Postgraduate Symposium, 7
Dec. 2006. The |
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Leong
V.Y.L., Hung S.C., Tsui Y.K., Lee M.K., Li L...C., Lo G...G., Masuda
K., Wu E...X., Luk K.D.K., Chan D. and Cheung K.M.C., Allogenic Mesenchymal
Stem Cell Transplantation Into The Intervertebral Disc: Effect Of Severity Of
Degeneration And Cell Number On Regeneration , International Society for
the Study of the Lumbar Spine. 34th Annual Meeting. |
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Leung Y.L., Wu E.X., Luk K.D.K., Chan D. and Cheung K.M.C., Allogeneic mesenchymal stem cell transplantation into the intervertebral disc: effect of severity of degeneration and cell number on regeneration, The Annual Meeting of the International Society for the Study of the Lumbar Spine. 2007. |
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Leung Y.L., Wu E.X., Luk K.D.K., Chan D. and Cheung K.M.C., Regeneration of degenerated intervertebral disc using allogeneic Mesenchymal stem cells encapsulated in self-assembling peptide hydrogel, 53rd Annual Meeting of the Orthopaedic Research Society. 2007. |
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Melhado I.G., Cheah K.S.E., Chan D., Tsang K.Y., Chan W.C.W. and Wang C., Towards an understanding of global gene expression changes in hypertrophic chondrocytes undergoing ER stress, Gordon Research Conference in Cartilage Biology. 2007. |
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Song Y., Cheung K.M.C., Ho D.W.H., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Yee A.F.Y., Poon S.C.S., 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 to lumbar disc degeneration in Chinese and Japanese., Gordon Research Conference on Cartilage Biology and Pathology, March 4-9, 2007, Ventura, CA, USA. 2007. |
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Song
Y., Cheung K.M.C., Fan B., Karppinen J., Yip S...P., Leong
J...C...Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., SNP-SNP Interaction in
Intervertebral Disc Disease with Genes in the Aggrecan Degradation Pathway, The
8th International Meeting on Human Genome Variation and Complex Genome
Analysis. Le Meridien Cyberport Hotel and Convention Centre, Hong Kong SAR, |
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Tsang K.Y., Chan D., Partanen J. and Cheah K.S.E., Fibroblast growth factor receptor 1 (FGFR1) regulates terminal differentiation of hypertrophic chondrocytes, Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 2007. |
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Tsang K.Y., Chan D., Cheslett D., Chan W.C.W., So C...L., Melhado I.G., Chan W.Y., Kwan K...M., Hunziker E...B., Yamada Y., Bateman J...F., Cheung K.M.C. and Cheah K.S.E., Surviving ER Stress is Coupled to Altered Chondrocyte Differentiation and Function., PLoS Biology. 2007, 5(3): 44. |
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Virtanen I...M., Song Y., Cheung K.M.C., Ala-Kokko L., Karppinen J., Ho D.W.H., Luk K.D.K., Yip S...P., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Chan D., Phenotypic and Population Differences in the Association between CILP and Lumbar Disc Disease., Journal of Medical Genetics. 2007, 44(4): 285-8. |
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Yang
F., Cheung K.M.C., Lu W.W., Leung Y.L., Chan D. and Luk K.D.K., A Simple Annular Puncture
Model Of Disc Degeneration In The Mouse Tail, International Society for
the Study of the Lumbar Spine. 34th Annual Meeting. |
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Yang
F., Chan D., Leong V.Y.L., Lu W.W., Luk K.D.K. and Cheung K.M.C., A Simple Novel Annular
Puncture Model of Disc Degeneration in the Mouse Tail., 11th Research
Postgraduate Symposium, 7 Dec. 2006. The |
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Yang
L., Chan D. and Cheah K.S.E., Genetic Analyses of
Terminal Differentiation of Hypertrophic Chondrocytes., 11th Research
Postgraduate Symposium, 7 Dec. 2006. The |
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Yee
A.F.Y., Cheung K.M.C. and Chan D., Protein Expression Profiles
of the Intervertebral Disc., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
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Yeung
C.W., Cheah K.S.E., Chan D. and Chan B.P., A novel 3-dimensional culture
system for mouse embryonic stem cells, International Society for Stem Cell
Research 5th Annual Meeting. Jun 15-21 2007. |
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Yeung
K.W.K., Chan Y.L., Lam K.O., Liu X.Y., Chung C.Y., |
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Yeung
K.W.K., Poon R.W.Y., Chung C.Y., Liu X.Y., |
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Yeung
K.W.K., Wu S.L., Liu X.M., Chung C.Y., |
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Yeung
K.W.K., Lam K.O., Chan Y.L., Wu S.L., Liu X.Y., Chung
C.Y., |
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Yeung
K.W.K., Chan Y.L., Lam K.O., Liu X.Y., Chung C.Y., |
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Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD: Integrated Cartilage Gene Database for genetic study of cartilage, BMC Genetics . 2007, 8: 4. |
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Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD:The Integrated Cartilage Gene Database., The Integrated Cartilage Gene Database. 2007. |
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Zhou
G., Yee A.F.Y., Chan D., Alini M. and Cheung K.M.C., Hypoxia-related and Stem
Cell-Like Phenotypes of Young, Adult and Aged Intervertebral Disc Cells, International
Society for the Study of the Lumbar Spine. 34th Annual Meeting. |
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Zhu
G., Chan D., Cheah K.S.E. and Huang J., KIF5b is Essential for Growth
Plate Organization, Cytokinesis and Chondrocytes Differentiation., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
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Researcher
: Chan JKM |
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List of Research Outputs |
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Chan
J.K.M., Chan
D. and Zhou Z., Functional Role
of MT1-MMP in FGF Signaling., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
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Researcher
: Chan KT |
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Project Title: |
Investigation of novel RNA-mediated regulation of Hoxb3 gene expression profiles |
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Investigator(s): |
Chan KT, Sham MH |
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Department: |
Biochemistry |
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Source(s) of Funding: |
Small Project Funding |
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Start Date: |
11/2005 |
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Completion Date: |
11/2006 |
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Abstract: |
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Hox homeobox genes are transcription factor genes with a clustered genomic organization in both mouse and human. The temporal and spatial specific expressions of Hox genes are essential for their function in regulating a variety of embryonic developmental processes. Recent studies on micro RNA genes in mammalian genomes demonstrated that there are a number of micro RNA genes present within Hox gene clusters. These micro RNA products have specific functions in regulating the expressions of target Hox genes, suggesting that apart from known regulatory mechanisms, RNA-mediated gene expression regulation is important of normal Hox gene function. To investigate RNA mediated control of Hox gene expression, we have performed pilot experiments by both in-silico and experimental approaches. From available databases, we have identified wide-spread conserved anti-sense RNA transcripts in all four Hox gene clusters in the mouse and human genomes, suggesting that these anti-sense RNAs may have important functions in Hox gene regulation. Moreover, we have identified a novel Hoxb3 anti-sense RNA which is expressed in a tissue-specific manner during mouse neural development. Similar anti-sense RNA transcript expression has also been observed for the human HoxA3 gene. Based on these observations, we hypothesize that these anti-sense RNA transcripts may be important for regulating Hox gene expression; and that RNA sequence mediated gene regulation may be a common mechanism for Hox gene regulation. The specific objectives of this project are: (1) To build up a complete expression profile of the differential mRNA transcripts for Hox genes; (2) To characterize both the structure and the expression patterns of the Hoxb3 anti-sense RNA transcript at different stages of mouse embryogeneis; (3) To perform a cell based functional analysis to examine the effect of anti-sense RNA on the expression of the normal Hoxb3 sense mRNA transcript. |
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List of Research Outputs |
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Chan K.T., Sae-Pang J.J., Tsang S.L., Tsang W.H., Kahmeyer-Gabbe M. and Sham M.H., A Hoxb3Mouse Mutant with Abnormal Thoracic Body Wall Development , Mouse Molecular Genetics August 30-September 3, 2006 Cold Spring Harbour, New York. 2006. |
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Sae-Pang J.J., Chan K.T., Tsang S.L., Tsang W...H. and Sham M.H., Cardiac developmental defects in a Hoxb mouse mutant Hoxb3lacZ, MGH-HKU-Nature China Forum, Hong Kong, March 2007. |
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Researcher
: Chan LC |
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List of Research Outputs |
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Au W.Y., Lam V.M.S., Pang A.W.K., Lee W.M., Chan L.C., Song Y., Ma E.S.K. and Kwong Y.L., Glucose-6-phosphate dehydrogenase deficiency in female octogenarians, nanogenarians, and centenarians, The Journals of Gerontology Series A: Biological Sciences and Medical Sciences . 2006, 61(10): 1086-1089. |
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Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Lu L...W., Chan L.C. and Sham M.H., Hoxb3 mutation leads to interleukin-6 dependent plasmacytoma., The 19th Meeting of the European Association for Cancer Research, Budapest, Hungary. July 2006. |
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Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Chan L.C., Lu L...W. and Sham M.H., The impact of Hoxb3 mutation on plasmacytoma., The 36th Annual Meeting of the Japanese Society for Immunology, Osaka, Japan. December, 2006. |
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List of Research Outputs |
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Chan
N.S., Leung
K.K.H., Bell D., Koopman P., Lovell=Badge R. and Cheah K.S.E., The Roles of Sox2 and Sox |
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Chan N.S., The Roles of Sox2 and Sox |
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List of Research Outputs |
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Chan
N.S., Leung
K.K.H., Bell D., Koopman P., Lovell=Badge R. and Cheah K.S.E., The Roles of Sox2 and Sox |
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Chan N.S., The Roles of Sox2 and Sox |
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Researcher
: Chan SF |
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List of Research Outputs |
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Ching Y.P., Chan S.F., Jeang K.T. and Jin D., Retroviral oncoprotein Tax targets coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication., Nature Cell Biology. 2006, 8: 717-724. |
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Researcher
: Chan SY |
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List of Research Outputs |
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Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD: Integrated Cartilage Gene Database for genetic study of cartilage, BMC Genetics . 2007, 8: 4. |
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Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD:The Integrated Cartilage Gene Database., The Integrated Cartilage Gene Database. 2007. |
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Researcher
: Chan WCW |
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List of Research Outputs |
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Chan W.C.W., Ng V.C.W., Wang C., Tsang K.Y., Cheah K.S.E. and Chan D., ER-stress signaling in the pathogenesis of Schmid metaphyseal chondrodysplasia , Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 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., 11th Research Postgraduate Symposium, 7 Dec. 2006. The |
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Chik
H.H.Y., Tsang K.Y., Cheng Y.W., Chan W.C.W., Cheah K.S.E. and Chan D., Genomic Analysis of Increased
Osteoblast Activity in a Mouse with generalized Hyperostosis., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
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Melhado I.G., Cheah K.S.E., Chan D., Tsang K.Y., Chan W.C.W. and Wang C., Towards an understanding of global gene expression changes in hypertrophic chondrocytes undergoing ER stress, Gordon Research Conference in Cartilage Biology. 2007. |
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Tsang K.Y., Chan D., Cheslett D., Chan W.C.W., So C...L., Melhado I.G., Chan W.Y., Kwan K...M., Hunziker E...B., Yamada Y., Bateman J...F., Cheung K.M.C. and Cheah K.S.E., Surviving ER Stress is Coupled to Altered Chondrocyte Differentiation and Function., PLoS Biology. 2007, 5(3): 44. |
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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., A Proteomic Approach To Study The Molecular Mechanisms Of The Unfolded Protein Response In The Endoplasmic Reticulum Of Chondrocytes, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU . 2006. |
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List of Research Outputs |
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Tsang K.Y., Chan D., Cheslett D., Chan W.C.W., So C...L., Melhado I.G., Chan W.Y., Kwan K...M., Hunziker E...B., Yamada Y., Bateman J...F., Cheung K.M.C. and Cheah K.S.E., Surviving ER Stress is Coupled to Altered Chondrocyte Differentiation and Function., PLoS Biology. 2007, 5(3): 44. |
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Researcher
: Chau CH |
|
List of Research Outputs |
|
Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chau C.H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4th Congress of FAONS, Nov13-Dec2, Hong Kong. 2006, 13. |
|
Liu H., Liu J., Chan C., Chau C.H., Chan Y.S. and Shum D.K.Y., Chondroitin sulfate moieties that are upregulated in Schwann cell-astrocyte encounters, Gordon research Conference on Proteoglycans July 9-14 Andover, New Hampshire, USA. 2006. |
|
Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of heparanase in the normal versus injured spinal cord of adult rats, Soc. Neuroscience Abstract (U.S.A.). 2006, 720: 12. |
|
Zhang
Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of
heparanase in the normal versus injured spinal cord of adult rats, Society
for Neuroscience ( |
|
Zhang
Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of
heparanase in the normal versus injured spinal cord of adult rats, Society
for Neuroscience Abstracts ( |
|
Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Expression patterns of heparanase in normal and injured rat spinal cord, Proceedings of the 4th Congress of FAONS. 2006, 67. |
|
Zhang Y., Yeung M.N., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats, J. Comparative Neurology. 2006, 494: 345-357. |
|
Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Proceedings of the 4th Congress of FAONS, Proceedings of the 4th Congress of FAONS. 2006, 67. |
|
Researcher
: Chau PPY |
|
List of Research Outputs |
|
Chau
P.P.Y., Krishnan
V., Cheah K.S.E. and Zhou Z., A Comparison of genomic
Instability in Laminopathy-specific Lamin A Mutations., 11th Research
Postgraduate Symposium, 7 Dec. 2006. The |
|
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: |
The regulation
and role of Sox |
|
Investigator(s): |
Cheah KSE |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
10/2002 |
|
Completion Date: |
09/2006 |
|
Abstract: |
|
The current project will test some hypotheses of Sox2 function using gene mapping, comparative genomics, genetics and transgenesis to: - i) identify the chromosomal breakpoints in Lcc; ii) identify the mutations in Ysb and Lcc and determine whether these have disrupted cis-elements which regulate Sox2 expression in the inner ear and hair follicle; iii) validate these findings by functional rescue/mutagenesis/genetic experiments in transgenic mice; iv) identify the molecular developmental changes in inner ear hair cell and hair follicle morphogenesis. |
|
Project Title: |
Genetic manipulation and analyses of the regulation of chondrocyte hypertrophy |
|
Investigator(s): |
Cheah KSE, Chan D |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
09/2003 |
|
Abstract: |
|
To understand the roles of Ihh and Ppr specifically in hypertrophic chondrocytes (HCs) and will dissect the mode of action of the Ihh and PPR pathways in HCs, in vivo, in transgenic and conditional knockout mice, Specially we will: 1) Investigate whether abnormal Ihh signaling and /or processing in 13del HCs is a primary cause of the differentiation abnormality by a) ablating Smoothened (Smo), the transducer of Ihh signaling in 13 del and wild-type HCs and b) over-expressing either Ihh or a non-secreted and unprocessed form of Ihh in normal HCs. 2) By the same rationale, study the role of the PTHrP/PPR pathway by ablating PPR in 13 del and wild-type HCs. |
|
Project Title: |
Functional analysis of SM22[beta] by tissue-specific targeted deletion in mice |
|
Investigator(s): |
Cheah KSE, Lau CP, Zhang JCL |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
09/2003 |
|
Abstract: |
|
To determine the general role of SM22[beta] in a cell; to understand the specific role of SM22[beta] in cardiovascular development. |
|
Project Title: |
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 B.P., Chan G.C.F., Wong H.L., Cheung P.T., Cheah K.S.E. and Chan D., Cell-Matrix Microsphere, Associated Products, Methods for Preparation and Applications., US Regular Patent Application No. 11/750,863 (filed on 18 May 2007).. 2007. |
|
Chan C.S.L., Leung C.M., Wong L.Y., Chan D., Cheah K.S.E. and Tanner J.A., Purification and Identification of Sclerostin Interacting Partners: Steps towards Osteoporosis Therapy with Aptamer-based Inhibitors, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU . 2006. |
|
Chan D., Gao B., Hu J., Law S.K.F., He L. and Cheah K.S.E., Abnormal IHH signaling affects distal digit patterning in a mouse model with brachydactyly type A1, FECTS XXth & ISMB meeting July 1-5, Oulu, Finland . 2006. |
|
Chan
N.S., Leung K.K.H., Bell D.,
Koopman P., Lovell=Badge R. and Cheah
K.S.E., The Roles of Sox2 and Sox |
|
Chan W.C.W., Ng V.C.W., Wang C., Tsang K.Y., Cheah K.S.E. and Chan D., ER-stress signaling in the pathogenesis of Schmid metaphyseal chondrodysplasia , Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 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., 11th Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Chan W.L., Chan D., Lee S., Cheah K.S.E. and Tanner J.A., A Proteomic Approach To Study The Molecular Mechanisms Of The Unfolded Protein Response In The Endoplasmic Reticulum Of Chondrocytes, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU . 2006. |
|
Chau
P.P.Y., Krishnan V., Cheah K.S.E. and Zhou Z., A Comparison of genomic
Instability in Laminopathy-specific Lamin A Mutations., 11th Research
Postgraduate Symposium, 7 Dec. 2006. The |
|
Cheah K.S.E., Development Growth & Differentiation (DGD), 2006. |
|
Cheah K.S.E., Gene locus involved in regulating hair pigmentation, vestibular function and fertility., European Patent No. 1148128. 2006. |
|
Cheah
K.S.E., Genes and molecular mechanisms in
development., HKU-University of |
|
Cheah K.S.E., Au Y.K., Wynn S.L., Geng G...Y...H. and Cheung K.M.C., Insight into the molecular pathogenesis of campomelic dysplasia revealed by a conditional Sox9 mutant mouse model. , Cold Spring Harbor Meeting on Mouse Molecular Genetics, Cold Spring Harbor, 30 Aug - 3 Sept 2006 New York, USA. 2006. |
|
Cheah K.S.E., Insights into the molecular pathogenesis of human skeletal dysplasias revealed by mouse models., XXth Federation of European Connective Tissue C, University of Oulu, 1-5 July 2006, Oulu, Finland . 2006. |
|
Cheah
K.S.E., Insights into the regulation of the
Col |
|
Cheah
K.S.E., RER stress in the growth plate., Gordon
Research Conference on Cartilage Biology and Pathology, March 4-9, 2007, |
|
Cheah
K.S.E., Sox2 is required for sensory organ
development in the mammalian inner ear, 2006 Research Output Prize, LSF
Faculty of Medicine, The University of |
|
Cheah
K.S.E., Understanding degenerative
intervertebral disc disease through devlopmental genetics and genomics., International
Society for the Study of the lumbar Spine, June 10-14, 2007 |
|
Cheah
K.S.E., Understanding the molecular
pathogenesis of skeletal dysplasia though mouse models., 11th
International Congress of Human Genetics (ICHG), 6-10 August 2006 |
|
Cheung K.M.C., Chan D., Karppinen J., Chen Y.Q., Jim J.J.T., Yip S.P., Ott J., Wong K.K., Sham P.C., Luk K.D.K., Cheah K.S.E., Leong J.C.Y. and Song Y., Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population, Spine. 2006, 31(10): 1143-1148. |
|
Cheung K.M.C., Luk K.D.K., Ho D.W.H., Chan D., Cheah K.S.E. and Song Y., Linkage analysis on familial early-onset degenerative disc disease. , Best Poster Award. 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong.. 2007. |
|
Cheung
K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S...P., Cheong
J...C...Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan
degradation pathway act synergistically to predispose to degenerative disc
disease., International Society for the Study of the Lumbar Spine. 34th
annual Meeting, June 10-14, 2007 |
|
Cheung K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S.P., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan degraduation pathway act synergistically to predispose to degenerative disc disease, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 2007. |
|
Chik
H.H.Y., Tsang K.Y., Cheng Y.W., Chan W.C.W., Cheah K.S.E. and Chan D., Genomic Analysis of Increased
Osteoblast Activity in a Mouse with generalized Hyperostosis., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Choi
M.Y., Chan C.C.Y., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Molecular Mechanism of
Disease for Spondyloepiphyseal Dysplasia Tarda-Effect of Mutations on sedlin
structure and Function., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
|
Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S...P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on Familial Early-Onset Degenerative Disc Disease (DDD)., ABS#apbc056 Jan14-17. 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, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 2007. |
|
Ho M...S., Tsang K.Y., Lo R.L.K., Susic M., Makitie O., Chan
T...W., Ng V.C.W., Sillence D...O.,
Boot-Handford R...P., Gibson G., Cheung K...M., Cole W...G., Cheah K.S.E. and Chan D., COL |
|
Huang J., Zhu G., Cheah K.S.E. and Chan D., KIF5b is essential for growth plate organization, cytokinesis and chondrocytes differentiation., Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 2007. |
|
Kao P.Y.P., Chan D., Cheung K.M.C., Cheah K.S.E., Sham P.C. and Song Y., Investigating Epistasis in Degenerative Disc Disease., ABS#apbc101 Jan 14-17, 2007. |
|
Kwong
W.H. and Cheah K.S.E.,
Functional Analyses of Type II Procollagen in Mouse Inner Ear Development., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Lee
B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tang L.F., Song Y. and Tanner J.A., Functional Study of
Cerberus-like and Noggin Proteins: toward a Biochemical Understanding of BMP
Antagonists in Skeletal Disorders, 11th Research Postgraduate Symposium, 7
Dec. 2006. The |
|
Li J.,
Cheah K.S.E. and Zhou Z., Bone Fracture Healing in
Laminopathy-based Premature Aging, 11th Research Postgraduate Symposium, 7
Dec. 2006. The |
|
Melhado I.G., Cheah K.S.E., Chan D., Tsang K.Y., Chan W.C.W. and Wang C., Towards an understanding of global gene expression changes in hypertrophic chondrocytes undergoing ER stress, Gordon Research Conference in Cartilage Biology. 2007. |
|
Pelling
A.L., Leung K.K.H., Tang A.S.P. and Cheah K.S.E., Faculty Outstanding
Research Output Award, Faculty of Medicine, The University of |
|
Song Y., Cheung K.M.C., Ho D.W.H., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Yee A.F.Y., Poon S.C.S., 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 to lumbar disc degeneration in Chinese and Japanese., Gordon Research Conference on Cartilage Biology and Pathology, March 4-9, 2007, Ventura, CA, USA. 2007. |
|
Song
Y., Cheung K.M.C., Fan B., Karppinen J., Yip S...P., Leong
J...C...Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., SNP-SNP Interaction in
Intervertebral Disc Disease with Genes in the Aggrecan Degradation Pathway, The
8th International Meeting on Human Genome Variation and Complex Genome
Analysis. Le Meridien Cyberport Hotel and Convention Centre, Hong Kong SAR, |
|
Tang L.F., Tang A.Y.B., Cheah K.S.E. and Song Y., Identification of a genetic modifier of CHD in Type IIA procollagen deficient mutant mice., ICSB 2006, Oct9-13, 2006, Yokohama, Japan. 2006. |
|
Tang
L.F., Tang A.Y.B., Cheah K.S.E. and Song Y., Identification of a genetic
modifier of CHD in Type IIA procollagen deficient mutant mice, Travel
Award. The 7th International Conferernce on Systems Biology. |
|
Tang
L.F., Cheah K.S.E. and Song Y., Mapping of a Genetic Modifier
of Congenital Heart Defect in Type IIA Procollagen Deficient Mice, 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Tang
L.F., Cheah K.S.E. and Song Y., Mapping of genetic modifier of congenital
heart defects in type IIA procollagen deficient mice., APBC2007, |
|
Tsang K.Y., Chan D., Partanen J. and Cheah K.S.E., Fibroblast growth factor receptor 1 (FGFR1) regulates terminal differentiation of hypertrophic chondrocytes, Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 2007. |
|
Tsang K.Y., Chan D., Cheslett D., Chan W.C.W., So C...L., Melhado I.G., Chan W.Y., Kwan K...M., Hunziker E...B., Yamada Y., Bateman J...F., Cheung K.M.C. and Cheah K.S.E., Surviving ER Stress is Coupled to Altered Chondrocyte Differentiation and Function., PLoS Biology. 2007, 5(3): 44. |
|
Tsang
S.W., Leung P...S., Cheah K.S.E.,
Thomas M...K. and Yao K.M.,
Involvement of PDZD |
|
Virtanen I...M., Song Y., Cheung K.M.C., Ala-Kokko L., Karppinen J., Ho D.W.H., Luk K.D.K., Yip S...P., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Chan D., Phenotypic and Population Differences in the Association between CILP and Lumbar Disc Disease., Journal of Medical Genetics. 2007, 44(4): 285-8. |
|
Watt R.M., Wang J., Leong M.K., Kung H...F., Cheah K.S.E., Liu D., Danchin A.L.M. and Huang J., Visualizing the proteome of Escherichia coli: an efficient and versatile method for labeling chromosomal coding DNA sequences (CDSs) with fluorescent protein genes., Nucleic Acids Research. 2007, 35(6): 1-11. |
|
Yang
L., Chan D. and Cheah K.S.E., Genetic Analyses of
Terminal Differentiation of Hypertrophic Chondrocytes., 11th Research
Postgraduate Symposium, 7 Dec. 2006. The |
|
Yeung
C.W., Cheah K.S.E., Chan D. and Chan B.P., A novel 3-dimensional culture
system for mouse embryonic stem cells, International Society for Stem Cell
Research 5th Annual Meeting. Jun 15-21 2007. |
|
Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD: Integrated Cartilage Gene Database for genetic study of cartilage, BMC Genetics . 2007, 8: 4. |
|
Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD:The Integrated Cartilage Gene Database., The Integrated Cartilage Gene Database. 2007. |
|
Zhu
G., Chan D., Cheah K.S.E. and Huang J., KIF5b is Essential for Growth Plate
Organization, Cytokinesis and Chondrocytes Differentiation., 11th Research
Postgraduate Symposium, 7 Dec. 2006. The |
|
Researcher
: Chee DMC |
|
List of Research Outputs |
|
Chee
D.M.C., Law
M.L., Tsang W.H., Tam P.K.H., Lui V.C.H. and Sham M.H., Study of the Impact of Sox10
Mutation on the Development of Enteric Nervous System in a Mutant Mouse Model
Generated by Gene Targeting., 11th Research Postgraduate Symposium, 7 Dec.
2006. 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 MH |
|
List of Research Outputs |
|
Cheng M.H., Mapping the locus for a novel blind mouse mutant Mcc, M.Med Science Dissertation. 2006. |
|
Sham M.H., Cheng M.H., Chao Z., Tsang S.L., Chan C.P., Choy R...K...W. and Song Y., Mapping the locus for a novel cataract mouse mutant with microphthalmia and closed eyelid., HUGO 12th Human Genome Meeting, Montreal, Canada. May, 2007. |
|
Researcher
: Cheng YW |
|
List of Research Outputs |
|
Chik
H.H.Y., Tsang K.Y., Cheng Y.W., Chan W.C.W., Cheah K.S.E. and Chan D., Genomic Analysis of Increased
Osteoblast Activity in a Mouse with generalized Hyperostosis., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Researcher
: Chik HHY |
|
List of Research Outputs |
|
Chik
H.H.Y., Tsang
K.Y., Cheng Y.W., Chan W.C.W., Cheah K.S.E. and Chan D., Genomic Analysis of Increased
Osteoblast Activity in a Mouse with generalized Hyperostosis., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Researcher
: Chin KT |
|
List of Research Outputs |
|
Chan C.P., Siu K.L., Chin K.T., Yuen K.Y., Zheng B. and Jin D., Modulation of the unfolded protein response by severe acute respiratory syndrome coronavirus spike protein., Journal of Virology. 2006, 80: 9279-9287. |
|
Chin K.T., Xu H., Ching Y.P. and Jin D., Differential subcellular localization and activity of kelch repeat proteins KLHDC1 and KLHDC2, Molecular and Cellular Biochemistry. Springer, 2007, 296: 109-119. |
|
Chin K.T., Chun C.S., Ching Y.P., Jeang K.T. and Jin D., Human T-cell leukemia virus oncoprotein represses nuclear receptor-dependent transcription by targeting coactivator TAX1BP1, Cancer Research. 2007, 67: 1072-1081. |
|
Siu Y.T., Chin K.T., Siu K.L., Choy E.Y.W., Jeang K.T. and Jin D., TORC1 and TORC2 coactivators are required for Tax activation of the human T-cell leukemia virus type 1 long terminal repeats., Journal of Virology . 2006, 80: 7052-7059. |
|
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.C.Y., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Molecular Mechanism of
Disease for Spondyloepiphyseal Dysplasia Tarda-Effect of Mutations on sedlin
structure and Function., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
|
Researcher
: Choy EYW |
|
List of Research Outputs |
|
Siu Y.T., Chin K.T., Siu K.L., Choy E.Y.W., Jeang K.T. and Jin D., TORC1 and TORC2 coactivators are required for Tax activation of the human T-cell leukemia virus type 1 long terminal repeats., Journal of Virology . 2006, 80: 7052-7059. |
|
List of Research Outputs |
|
Chu J.Y.S., Lee L.T., Lai S.K., Chan Y.S., Yung W.H. and Chow B.K., The hypothalamo-neurohypophsial secretinergic pathway in regulating body water homeostasis, Proceedings of the 4th Congress of FAONS. 2006, 108-109. |
|
Researcher
: Chun CS |
|
List of Research Outputs |
|
Chin K.T., Chun C.S., Ching Y.P., Jeang K.T. and Jin D., Human T-cell leukemia virus oncoprotein represses nuclear receptor-dependent transcription by targeting coactivator TAX1BP1, Cancer Research. 2007, 67: 1072-1081. |
|
Chun
C.S. and Jin
D., Characterisation of MAD2B., 11th Research Postgraduate Symposium,
7 Dec. 2006. The |
|
Researcher
: Danchin ALM |
|
List of Research Outputs |
|
Huang
J., Watt R.M., Wang J., Leong M.K., Liu D. and Danchin A.L.M., Visualizing
becterial proteomes., 14th International Molecular Medicine Tri-Conference.
Feb 27-Mar 2 San Franciso, CA, |
|
Watt R.M., Wang J., Leong M.K., Kung H...F., Cheah K.S.E., Liu D., Danchin A.L.M. and Huang J., Visualizing the proteome of Escherichia coli: an efficient and versatile method for labeling chromosomal coding DNA sequences (CDSs) with fluorescent protein genes., Nucleic Acids Research. 2007, 35(6): 1-11. |
|
Researcher
: Fan B |
|
List of Research Outputs |
|
Cheung K.M.C., Fan B., Karppinen J., Leong J.C.Y. and Luk K.D.K., Can age-related interverterbal disc changes be differentiated from degenerative disc disease?, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 2007. |
|
Cheung
K.M.C., Karppinen J., Guo G...G., Fan
B., Leong J.C.Y. and Luk K.D.K., Relationship Between MRI
Changes of The Lumbar Spine and Low Back Pain: A MRI Study of 1043
Population-Based Subjects., International Society for the Study of the
Lumbar Spine. 34th Annual Meeting. |
|
Cheung K.M.C., Karppinen J., Guo G.G., Fan B., Leong J.C.Y. and Luk K.D.K., Relationship between MRI changes of the lumbar spine and low back pain: a MRI study of 1043 population-based subjects, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 2007. |
|
Cheung
K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S...P.,
Cheong J...C...Y., Luk K.D.K., Ott J.,
Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan
degradation pathway act synergistically to predispose to degenerative disc
disease., International Society for the Study of the Lumbar Spine. 34th
annual Meeting, June 10-14, 2007 |
|
Cheung K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S.P., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan degraduation pathway act synergistically to predispose to degenerative disc disease, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 2007. |
|
Song
Y., Cheung K.M.C., Fan B., Karppinen J., Yip S...P.,
Leong J...C...Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., SNP-SNP Interaction in
Intervertebral Disc Disease with Genes in the Aggrecan Degradation Pathway, The
8th International Meeting on Human Genome Variation and Complex Genome
Analysis. Le Meridien Cyberport Hotel and Convention Centre, Hong Kong SAR, |
|
Researcher
: Gao B |
|
List of Research Outputs |
|
Chan D., Gao B., Hu J., Law S.K.F., He L. and Cheah K.S.E., Abnormal IHH signaling affects distal digit patterning in a mouse model with brachydactyly type A1, FECTS XXth & ISMB meeting July 1-5, Oulu, Finland . 2006. |
|
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., Luk K.D.K., Ho D.W.H., Chan D., Cheah K.S.E. and Song Y., Linkage analysis on familial early-onset degenerative disc disease. , Best Poster Award. 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong.. 2007. |
|
Cheung
K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S...P., Cheong
J...C...Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan
degradation pathway act synergistically to predispose to degenerative disc
disease., International Society for the Study of the Lumbar Spine. 34th
annual Meeting, June 10-14, 2007 |
|
Cheung K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S.P., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan degraduation pathway act synergistically to predispose to degenerative disc disease, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 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 (DDD)., ABS#apbc056 Jan14-17. 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, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 2007. |
|
Song Y., Cheung K.M.C., Ho D.W.H., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Yee A.F.Y., Poon S.C.S., 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 to lumbar disc degeneration in Chinese and Japanese., Gordon Research Conference on Cartilage Biology and Pathology, March 4-9, 2007, Ventura, CA, USA. 2007. |
|
Virtanen I...M., Song Y., Cheung K.M.C., Ala-Kokko L., Karppinen J., Ho D.W.H., Luk K.D.K., Yip S...P., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Chan D., Phenotypic and Population Differences in the Association between CILP and Lumbar Disc Disease., Journal of Medical Genetics. 2007, 44(4): 285-8. |
|
Researcher
: Hu J |
|
List of Research Outputs |
|
Chan D., Gao B., Hu J., Law S.K.F., He L. and Cheah K.S.E., Abnormal IHH signaling affects distal digit patterning in a mouse model with brachydactyly type A1, FECTS XXth & ISMB meeting July 1-5, Oulu, Finland . 2006. |
|
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. |
|
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, |
|
List of Research Outputs |
|
Du L., He Y., Wang Y., Zhang H., Ma S., Wong C...K., Wu S...H., Ng F., Huang J., Yuen K...Y., Jiang S., Zhou Y. and Zheng B...J., Recombinant adeno-associated virus expressing the receptor-binding domain of severe acute respiratory syndrome coronavirus S Protein elicits neutralizing antibodies:Implication for developing SARS vaccines., Virology. 2006, 353(1): 6-16. |
|
Du L., He Y., Wang Y., Zhang H., Ma S., Wong K.L., Wu H.W., Ng F., Huang J., Yuen K.Y., Jiang S., Zhou Y. and Zheng B., Strong antigenicity and neutralizing antibody induced by recombinant Recombinant adeno-associated virus expressing the receptor-binding domain of severe acute respiratory syndrome coronavirus S protein elicits protective neutralizing antibodies: implication for developing SARS vaccines., Vorology. 2006, 353(1): 6-16. |
|
Ge R., Sun X., Gu Q., Watt R.M., Tanner J.A., Wong B...C...Y., Xia H...H., Huang J., He Q. and Sun H., A Proteomic Approach for Identification of Bismuth-binding Proteins in Helicobacter pylori., Journal of Biological Inorganic Chemistry. 2007, 12: 831-842. |
|
Ge R., Zhang Y., Sun X., Watt R.M., He Q., Huang J., Wilcox D.E. and Sun H., Thermodynamic and kinetic aspects of metal binding to the histidine-rich protein, Hpn, Journal of the American Chemical Society. 2006, 128: 11330-11331. |
|
Huang
J., Fluorescence Microscopic Study of Kinesin
I-Mediated Intracellular Transportation., 2nd Annual Advanced Optical
Methods Workshop. May 28-31, 2007, |
|
Huang
J., Intracellular transportation in diseases
and development., HKU-University of |
|
Huang J., Zhu G., Cheah K.S.E. and Chan D., KIF5b is essential for growth plate organization, cytokinesis and chondrocytes differentiation., Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 2007. |
|
Huang
J., Mouse models of intracellular
transportation deficiency: |
|
Huang
J., Mouse models of intracellular
transportation deficiency: |
|
Huang
J., Mouse models of intracellular
transportation deficiency: |
|
Huang
J., Mouse models of intracellular
transportation deficiency: |
|
Huang
J., Recombineering: a novel DNA Engineering
Technology, |
|
Huang
J., Recombineering: a novel DNA Engineering
Technology, |
|
Huang
J., Recombineering: a novel DNA Engineering
Technology, |
|
Huang
J., Watt
R.M., Wang J., Leong M.K., Liu D. and Danchin A.L.M., Visualizing becterial
proteomes., 14th International Molecular Medicine Tri-Conference. Feb
27-Mar 2 San Franciso, CA, |
|
Huang
J., 細胞內運輸系統與疾病, |
|
Huen M...S...Y., Lu L., Liu D. and Huang J., Active transcription promotes single-stranded oligonucleotide mediated gene repair., Biochemiscal and Biophysical Research Communications. 2007, 353(1): 33-39. |
|
Huen M...S...Y., Li X., Lu L., Watt R.M., Liu D. and Huang J., The involvement of replication in single stranded oligonucleotide-mediated gene repair., Nucleic Acids Research. 2006, 34(21): 6183-6194. |
|
Liu
C., Xie L...X., Huang J.,
Liao F...L., Liu L., Goto S. and Li M., Protective Effects of Chinese
Medicine Salvianolic Acid B, Astragaloside IV, and Daillyl Trisulfide on Endothelial
Cells against damage induced by H2O2., The
2nd International Conference of Cardiovascular Specialty Committee. World
federation of Chinese Medicine Societies Cordiovascular Specialty Specialty
Committee. Oct 21-22, 2006 |
|
Liu
C., Xie L...X., Huang J.,
Liao F...L., Liu L., Goto S. and Li M., Protective effects of Salvianolic
acid B, Astragaloside IV, and DT on endothelial cells against damage induced
by H2O2, The 4th Asian-Pacific Congress on Thrombosis and Hemostasis.
September 21-23, 2006. |
|
Ni Y.,
Liu L...X., Qu J...L., Niu H...B., Li G. and Huang J., Axonal APP Interacts with
BACE in Anterograde Transport-Dependent Manner., 2007 World Congress on
Ageing and Dementia in Chinese Communities. March 7-10, 2007, Hong Kong SAR, |
|
Sui
H., Wong K.L., Huang J. and Zheng B., Long term expression of small
interfering RNA targeting M2 gene induces effective inhibition of influenza A
virus replication. , Options for the Control of Influenza VI Conference..
|
|
Sun
H., Ge R., Sun X., Xia H.H.X. and Huang J., Identification of
Metal-binding Proteins/Motifs in Microorganisms by Metalloproteome: an
Example for Bismuth, Gordon Research Conference, Metal in Medicine, |
|
Sun
H., Yang N., Ge R. and Huang J., Interactions of Bismuth
with Proteins And Enzymes: Insight into its Mechanism of Action, 37th
International Conference on Coordination Chemistry (ICCC-37, Keynote
Speaker), |
|
Sun
H., Yang N., Ge R. and Huang J., Interactions of bismuth
with proteins and enzymes: insight into its mechanism of action., 37thInternational
Conference on Coordination Chemistry (ICCCV-37) August 13-18, 2006, |
|
Sun H., Ge R., Zeng Y. and Huang J., The Role of Hpn and its Related Histidine-rich Proteins in Helicobacter pylori , 3rd Asian Biological Inorganic Chemistry Conference, Nanjing, P.R. China, October 30- November 3. 2006. |
|
Wang Z., Zhou Z., Liu D. and Huang J., Single-Stranded Oligonucleotide-Medicated Gene Repair in Mammalian Cells Has A Mechanism Distinct from Homologous Recombination Repair., 46th Annual Meeting of the American Society for Cell Biology. 2006. |
|
Wang Z., Zhou Z., Liu D. and Huang J., Single-Stranded Oligonucleotide-mediated gene repair in mammalian cells has a mechanism distinct from homologous recombination repair. , Biochemical and Biophysical Research Communications. BBRC, 2006, 350 (3): 568-573. |
|
Watt R.M., Wang J., Leong M.K., Kung H...F., Cheah K.S.E., Liu D., Danchin A.L.M. and Huang J., Visualizing the proteome of Escherichia coli: an efficient and versatile method for labeling chromosomal coding DNA sequences (CDSs) with fluorescent protein genes., Nucleic Acids Research. 2007, 35(6): 1-11. |
|
Xie L...X., Liu C., Huang J., Liao F...L., Liu L., Goto
S. and Li M., Anti-apoptosis effects of Chinese herbal medicine Salvianolic
Acid B (Sal B) on rat Cerebral Microvascular Endothelial Cells., The 4th
Asia-Pacific Congress on Thrombosis and Hemostasis. September 21-23, 2006. |
|
Yang N., Tanner J.A., Huang J., Zheng B...J. and Sun
H...Z., Inhibition of SARS Coronavirus by Bismuth Compounds., The 3rdAsian
Biological Inorganic Chemistry Conference(AsBIC-3) 31Oct-3 Nov. 2006, |
|
Yang N., Tanner J.A., Huang J., Zheng B. and Sun H., Inhibition of SARS Coronavirus by Bismuth Compounds, 3rd Asian Biological Inorganic Chemistry Conference, Nanjing, P.R. China, October 30- November 3. 2006. |
|
Zhu
G., Chan D., Cheah K.S.E. and Huang J., KIF5b is Essential for
Growth Plate Organization, Cytokinesis and Chondrocytes Differentiation., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Researcher
: Hung SC |
|
List of Research Outputs |
|
Leong
V.Y.L., Hung S.C., Tsui Y.K., Lee M.K., Li L...C., Lo G...G., Masuda
K., Wu E...X., Luk K.D.K., Chan D. and Cheung K.M.C., Allogenic Mesenchymal
Stem Cell Transplantation Into The Intervertebral Disc: Effect Of Severity Of
Degeneration And Cell Number On Regeneration , International Society for
the Study of the Lumbar Spine. 34th Annual Meeting. |
|
Researcher
: Jian X |
|
List of Research Outputs |
|
Jian
X., characterization of SARS Coronavirus
Helicase Metal Binding Domain., 11th Research Postgraduate Symposium, 7
Dec. 2006. The |
|
Researcher
: Jim JJT |
|
List of Research Outputs |
|
Aladin
Kaderbatcha D.M., Lu W.W., Chan D., Yee A.F.Y., Jim J.J.T., Luk K.D.K. and Cheung K.M.C., EXPRESSION OF THE TRP2
ALLELE OF COL |
|
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: |
Development of RNAi technology for inhibition of viral replication |
|
Investigator(s): |
Jin D |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Small Project Funding |
|
Start Date: |
11/2003 |
|
Completion Date: |
02/2007 |
|
Abstract: |
|
To use Sindbis virus as a model to systematically study RNAi-mediated inhibition of viral replication; to study the rules for selection of RNAi targets particularly effective for inhibition of viral replication in mammalian cells; to compare the effectiveness of siRNAs targeting UTR, non-structural (such as polymerase) or structural (such as capsid) regions. |
|
Project Title: |
Roles and regulation of peroxiredoxins: from yeast to human |
|
Investigator(s): |
Jin D |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
12/2003 |
|
Abstract: |
|
To perform in-depth analyses on the transcriptional regulation of yeast PMP20; to study the structure-function relationship of yeast and human peroxiredoxins; to characterize the impact of binding to heme on Tsa1p/Tsa2p function; to investigate the roles of peroxiredoxins in cell physiology and pathology. Out focus will be on apoptosis, aging and cell proliferation. |
|
Project Title: |
Roles 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. |
|
List of Research Outputs |
|
Chan C.P., Siu K.L., Chin K.T., Yuen K.Y., Zheng B. and Jin D., Modulation of the unfolded protein response by severe acute respiratory syndrome coronavirus spike protein., Journal of Virology. 2006, 80: 9279-9287. |
|
Chin K.T., Xu H., Ching Y.P. and Jin D., Differential subcellular localization and activity of kelch repeat proteins KLHDC1 and KLHDC2, Molecular and Cellular Biochemistry. Springer, 2007, 296: 109-119. |
|
Chin K.T., Chun C.S., Ching Y.P., Jeang K.T. and Jin D., Human T-cell leukemia virus oncoprotein represses nuclear receptor-dependent transcription by targeting coactivator TAX1BP1, Cancer Research. 2007, 67: 1072-1081. |
|
Ching Y.P., Leong V.Y.L., Lee M.F., Xu H., Jin D. and Ng I.O.L., P21-activated protein kinase is overexpressed in hepatocellular carcinoma and enhances cancer metastasis involving c-Jun NH2-terminal kinase activation and paxillin phosphorylation. , Cancer Research. 2007, 67: 3601-3608. |
|
Ching Y.P., Chan S.F., Jeang K.T. and Jin D., Retroviral oncoprotein Tax targets coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication., Nature Cell Biology. 2006, 8: 717-724. |
|
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. |
|
Chun
C.S. and Jin D.,
Characterisation of MAD2B., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
|
Jin D., A centrosomal target of HTLV-I Tax on the road to genome instability (Invited Plenary Lecture), 13th International Conference on Human Retrovirology: HTLV and Related Viruses. 2007. |
|
Jin D., A centrosomal target of HTLV-I Tax on the road to genome instability, AIDS Research and Human Retroviruses. Mary Ann Liebert, Inc., 2007, 23: 595. |
|
Jin D., A centrosomal target of human T-cell leukemia virus type I oncoprotein Tax on the road to genome instability, Cancer 2007, The Third Asia Pacific Multidisciplinary Meeting for Cancer Research and the Annual Scientific Meeting for Cancer Research, International Academy of Pathology, The Chinese University of Hong Kong, Hong Kong. 2007. |
|
Jin
D., A commentary on phylogenetic analysis of
H5N1 influenza A viruses. , H5N |
|
Jin D., Associate Editor, Asian Journal of Biochemistry. Academic Journals Inc., 2006. |
|
Jin
D., Centrosomal amplification and retroviral
oncogenesis., The Croucher Advanced Study Institute “Molecular Genetics
and Cell Signaling in Cancer and Cancer Metastasis”. The |
|
Jin D., Editorial Board Member (Academic Editor), PLoS ONE. Public Library of Science (PLoS), 2006. |
|
Jin D., Interactions between the human double-stranded RNA binding proteins, TRBP, PACT and Dicer to facilitate the production of siRNA. , RNAi 2007: The Expanding Roles of Small RNAs. St Anne’s College, Oxford, UK. 2007. |
|
Jin D., Managing Editor, Frontiers in Bioscience. Frontiers in Bioscience, 2006. |
|
Jin D., Molecular pathogenesis of hepatitis C virus-associated hepatocellular carcinoma, Frontiers in Bioscience. 2007, 12: 222-233. |
|
Jin D., Vertebrate viruses and microRNAs, 脊椎動物病毒與微RNA, Chemistry of Life. 生命的化學, Shanghai, Chinese Society of Biochemistry and Molecular Biology, 2007, 27: 105-108. |
|
Kok K.H., Ng M.H., Ching Y.P. and Jin D., Human TRBP and PACT directly interact with each other and associated with Dicer to facilitate the production of small interfering RNA , Journal of Biological Chemistry. 2007, 282: 17649-17657. |
|
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, In: Greg Hannon, Carlo Croce, Scott
Hammond, Keystone Symposium on MicroRNA and Cancer. Keystone Resort, |
|
Kok K.H. and Jin D., Influenza A virus NS1 protein does not suppress RNA interference in mammalian cells., Journal of General Virology. 2006, 87: 2639-2644. |
|
Li H., Fung K.L., Jin D., Chung S.S.M., Ching Y.P., Ng I.O.L., Sze K.H., Ko C.B. and Sun H., Solution Structures, Dynamics, and Lipid-binding of the Sterile a-Motif Domain of the Deleted in Liver Cancer 2, PROTEINS: Structure, Function, and Bioinformatics. 2007, 67: 1154-1166. |
|
Li Y.,
Chu L.W., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., Association of ABCA1 Gene with
Sporadic Alzheimer's Disease in Chinese Group and Potential Functional
Importance for Novel Intronic Polymorphism., 11th Research Postgraduate
Symposium, 7 Dec. 2006. The |
|
Siu Y.T., Chin K.T., Siu K.L., Choy E.Y.W., Jeang K.T. and Jin D., TORC1 and TORC2 coactivators are required for Tax activation of the human T-cell leukemia virus type 1 long terminal repeats., Journal of Virology . 2006, 80: 7052-7059. |
|
Siu Y.T. and Jin D., Tax-induced recruitment of TORC family coactivators is required for transcriptional activation of HTLV-I LTR (Young Scientists Award-winning presentation), 13th International Conference on Human Retrovirology: HTLV and Related Viruses. 2007. |
|
Siu Y.T. and Jin D., Tax-induced recruitment of TORC family coactivators is required for transcriptional activation of HTLV-I LTR, AIDS Research and Human Retroviruses. Mary Ann Liebert, Inc., 2007, 23: 646. |
|
Tang
V.H.M., Siu K.L. and Jin D., Peroxiredoxin-null Yeast
Cells are Hypersensitive to DNA-damaging Agents., 11th Research
Postgraduate Symposium, 7 Dec. 2006. The |
|
Yam J.W.P., Ko C.F., Chan C.Y., Jin D. and Ng I.O.L., Interaction of DLC1-tensin2 complex with caveolin-1 and implications in tumor suppression, Cancer Research. 2006, 66: 8367-8372. |
|
Yam J.W.P., Ko C.F., Chan C.Y., Yau T.O., Tung K.K., Leung T.H.Y., Jin D. and Ng I.O.L., Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma, Hepatology. 2006, 44: 881-890. |
|
Yam J.W.P., Ko C.F., Chan P.C.Y., Yau T.O., Tung K.K., Leung T.H.Y., Jin D. and Ng I.O.L., Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma, Queenstown Signal Transduction Meeting, New Zealand. 2006. |
|
Researcher
: Kao PYP |
|
List of Research Outputs |
|
Cheung
K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S...P., Cheong
J...C...Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan
degradation pathway act synergistically to predispose to degenerative disc
disease., International Society for the Study of the Lumbar Spine. 34th
annual Meeting, June 10-14, 2007 |
|
Cheung K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S.P., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan degraduation pathway act synergistically to predispose to degenerative disc disease, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 2007. |
|
Kao
P.Y.P., Sham
P.C., Chan D., Cheung K.M.C. and Song Y., Investigating Epistasis in
Degenerative Disc Disease., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
|
Kao P.Y.P., Chan D., Cheung K.M.C., Cheah K.S.E., Sham P.C. and Song Y., Investigating Epistasis in Degenerative Disc Disease., ABS#apbc101 Jan 14-17, 2007. |
|
Researcher
: Kok KH |
|
List of Research Outputs |
|
Kok K.H., Ng M.H., Ching Y.P. and Jin D., Human TRBP and PACT directly interact with each other and associated with Dicer to facilitate the production of small interfering RNA , Journal of Biological Chemistry. 2007, 282: 17649-17657. |
|
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, In: Greg Hannon, Carlo
Croce, Scott Hammond, Keystone Symposium on MicroRNA and Cancer. Keystone
Resort, |
|
Kok K.H. and Jin D., Influenza A virus NS1 protein does not suppress RNA interference in mammalian cells., Journal of General Virology. 2006, 87: 2639-2644. |
|
Kok K.H., Roles of Human Double-stranded RNA Binding Proteins TRBP and PACT in RNA Interference , PhD Thesis. 2006. |
|
List of Research Outputs |
|
Tsang
H.M., Kong C.T., Sham M.H. and Chan L.C., Analysis of Mll-Een Fusion
Gene in Mouse Leukemic Model, Keystone Symposium - Mouse Models at the
Frontiers of Cancer Discovery. Whistler Resort, Whistler, |
|
Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Lu L...W., Chan L.C. and Sham M.H., Hoxb3 mutation leads to interleukin-6 dependent plasmacytoma., The 19th Meeting of the European Association for Cancer Research, Budapest, Hungary. July 2006. |
|
Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Chan L.C., Lu L...W. and Sham M.H., The impact of Hoxb3 mutation on plasmacytoma., The 36th Annual Meeting of the Japanese Society for Immunology, Osaka, Japan. December, 2006. |
|
Researcher
: Krishnan V |
|
List of Research Outputs |
|
Chau
P.P.Y., Krishnan V., Cheah K.S.E. and Zhou Z., A Comparison of genomic
Instability in Laminopathy-specific Lamin A Mutations., 11th Research
Postgraduate Symposium, 7 Dec. 2006. The |
|
Krishnan V., Zhang L. and Zhou Z., Prelamin A Regulates DNA Repair and Senescence via Histone Modifications , 2007 Keystone Symposia Conference - Genome Instability and Repair. 2006. |
|
Researcher
: Kwok AWS |
|
List of Research Outputs |
|
Chan
C.H., Kwok A.W.S., Chan Y.S., Li X. and Shum D.K.Y., Upregulation of nitrated
chondroitin sulfate proteoglycans in reactive astrocytes and cerebrospinal
fluid of patients with amyotrophic lateral sclerosis, Proceedings of the
4th Congress of FAONS, Nov 30 - Dec 2, |
|
Researcher
: Kwok JCF |
|
List of Research Outputs |
|
Kwok J.C.F., Lau J.W.K., Ng K.Y., Shum D.K.Y. and Chan Y.S., Chondroitin sulfates enriched in the developing rat hindbrain restrict commissural projections of vestibular neurons, Neurosignals. 2006, 15: 123-123. |
|
Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chau C.H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4th Congress of FAONS, Nov13-Dec2, Hong Kong. 2006, 13. |
|
Lau J.W.K., Kwok J.C.F., Ng T...K., Chan Y.S. and Shum D.K.Y., Developing vestibular neurons display differential commissural projection patterns with digestion of chondroitin sulfates, Proceedings of the 4th Congress of FAONS Nov 30 - Dec 2, Hong Kong. 2006, 25. |
|
Researcher
: Kwong WH |
|
List of Research Outputs |
|
Kwong
W.H. and Cheah
K.S.E., Functional Analyses of Type II Procollagen in Mouse Inner Ear
Development., 11th Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Researcher
: Lai WL |
|
List of Research Outputs |
|
Lai W.L. and Wong N.S., The identification of sequence elements that mediate stabilization of the CHOP/Gadd153 mRNA by N-(4-hydroxyphenyl)retinamide (4HPR/fenretinide), AACR, April, 2007. |
|
Researcher
: Lam VMS |
|
List of Research Outputs |
|
Au W.Y., Lam V.M.S., Pang A.W.K., Lee W.M., Chan L.C., Song Y., Ma E.S.K. and Kwong Y.L., Glucose-6-phosphate dehydrogenase deficiency in female octogenarians, nanogenarians, and centenarians, The Journals of Gerontology Series A: Biological Sciences and Medical Sciences . 2006, 61(10): 1086-1089. |
|
Wang
X., Lam V.M.S. and Engel
P...C., Functional properties of two mutants of human glucose 6-phosphate
dehydrogenase, R |
|
Researcher
: Law ML |
|
List of Research Outputs |
|
Chee
D.M.C., Law M.L., Tsang W.H., Tam P.K.H., Lui V.C.H. and Sham M.H., Study of the Impact of Sox10
Mutation on the Development of Enteric Nervous System in a Mutant Mouse Model
Generated by Gene Targeting., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
|
Law M.L., Studying enteric nervous system development using the Sox10Dmouse mutant, PhD Thesis. 2006. |
|
Researcher
: Law SKF |
|
List of Research Outputs |
|
Chan D., Gao B., Hu J., Law S.K.F., He L. and Cheah K.S.E., Abnormal IHH signaling affects distal digit patterning in a mouse model with brachydactyly type A1, FECTS XXth & ISMB meeting July 1-5, Oulu, Finland . 2006. |
|
Researcher
: Lee BBC |
|
List of Research Outputs |
|
Lee
B.B.C., Chan
C.S.L., Chan D., Cheah K.S.E., Tang L.F., Song Y. and Tanner J.A., Functional Study of
Cerberus-like and Noggin Proteins: toward a Biochemical Understanding of BMP
Antagonists in Skeletal Disorders, 11th Research Postgraduate Symposium, 7
Dec. 2006. The |
|
Researcher
: Lee S |
|
List of Research Outputs |
|
Chan W.L., Chan D., Lee S., Cheah K.S.E. and Tanner J.A., A Proteomic Approach To Study The Molecular Mechanisms Of The Unfolded Protein Response In The Endoplasmic Reticulum Of Chondrocytes, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU . 2006. |
|
Researcher
: Leong JCY |
|
List of Research Outputs |
|
Cheung K.M.C., Chan D., Karppinen J., Chen Y.Q., Jim J.J.T., Yip S.P., Ott J., Wong K.K., Sham P.C., Luk K.D.K., Cheah K.S.E., Leong J.C.Y. and Song Y., Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population, Spine. 2006, 31(10): 1143-1148. |
|
Cheung
K.M.C., Karppinen J., Guo G...G., Fan
B., Leong J.C.Y. and Luk K.D.K., Relationship Between MRI
Changes of The Lumbar Spine and Low Back Pain: A MRI Study of 1043
Population-Based Subjects., International Society for the Study of the
Lumbar Spine. 34th Annual Meeting. |
|
Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S...P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on Familial Early-Onset Degenerative Disc Disease (DDD)., ABS#apbc056 Jan14-17. 2007. |
|
Song Y., Cheung K.M.C., Ho D.W.H., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Yee A.F.Y., Poon S.C.S., 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 to lumbar disc degeneration in Chinese and Japanese., Gordon Research Conference on Cartilage Biology and Pathology, March 4-9, 2007, Ventura, CA, USA. 2007. |
|
Virtanen I...M., Song Y., Cheung K.M.C., Ala-Kokko L., Karppinen J., Ho D.W.H., Luk K.D.K., Yip S...P., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Chan D., Phenotypic and Population Differences in the Association between CILP and Lumbar Disc Disease., Journal of Medical Genetics. 2007, 44(4): 285-8. |
|
Researcher
: Leong MK |
|
List of Research Outputs |
|
Huang
J., Watt R.M., Wang J., Leong M.K., Liu D. and Danchin A.L.M., Visualizing becterial
proteomes., 14th International Molecular Medicine Tri-Conference. Feb
27-Mar 2 San Franciso, CA, |
|
Watt R.M., Wang J., Leong M.K., Kung H...F., Cheah K.S.E., Liu D., Danchin A.L.M. and Huang J., Visualizing the proteome of Escherichia coli: an efficient and versatile method for labeling chromosomal coding DNA sequences (CDSs) with fluorescent protein genes., Nucleic Acids Research. 2007, 35(6): 1-11. |
|
Researcher
: Leong VYL |
|
List of Research Outputs |
|
Leong
V.Y.L., Hung
S.C., Tsui Y.K., Lee M.K., Li L...C., Lo G...G., Masuda
K., Wu E...X., Luk K.D.K., Chan D. and Cheung K.M.C., Allogenic Mesenchymal
Stem Cell Transplantation Into The Intervertebral Disc: Effect Of Severity Of
Degeneration And Cell Number On Regeneration , International Society for
the Study of the Lumbar Spine. 34th Annual Meeting. |
|
Yang
F., Chan D., Leong V.Y.L., Lu W.W., Luk K.D.K. and Cheung K.M.C., A Simple Novel Annular
Puncture Model of Disc Degeneration in the Mouse Tail., 11th Research
Postgraduate Symposium, 7 Dec. 2006. The |
|
Researcher
: Leung CM |
|
List of Research Outputs |
|
Chan C.S.L., Leung C.M., Wong L.Y., Chan D., Cheah K.S.E. and Tanner J.A., Purification and Identification of Sclerostin Interacting Partners: Steps towards Osteoporosis Therapy with Aptamer-based Inhibitors, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU . 2006. |
|
Shum
K.T., Leung C.M., Wong L.Y., Chan C.S.L. and Tanner J.A., New Approaches for
Therapeutic Aptamer Selection and Delivery, MGH-HKU-Nature |
|
Researcher
: Leung KKH |
|
List of Research Outputs |
|
Chan
N.S., Leung K.K.H., Bell
D., Koopman P., Lovell=Badge R. and Cheah
K.S.E., The Roles of Sox2 and Sox |
|
Pelling
A.L., Leung K.K.H., Tang A.S.P. and Cheah K.S.E., Faculty Outstanding
Research Output Award, Faculty of Medicine, The University of |
|
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 |
|
Researcher
: Li J |
|
List of Research Outputs |
|
Li
J., Cheah
K.S.E. and Zhou Z., Bone Fracture
Healing in Laminopathy-based Premature Aging, 11th Research Postgraduate
Symposium, 7 Dec. 2006. The |
|
Researcher
: Li X |
|
List of Research Outputs |
|
Chan C.H., Kwok A.W.S., Chan Y.S., Li X. and Shum D.K.Y., Upregulation of nitrated chondroitin sulfate proteoglycans in reactive astrocytes and cerebrospinal fluid of patients with amyotrophic lateral sclerosis, Proceedings of the 4th Congress of FAONS, Nov 30 - Dec 2, Hong Kong. 2006, 108. |
|
Huen M...S...Y., Li X., Lu L., Watt R.M., Liu D. and Huang J., The involvement of replication in single stranded oligonucleotide-mediated gene repair., Nucleic Acids Research. 2006, 34(21): 6183-6194. |
|
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., Chu
L.W., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., Association of ABCA1 Gene with
Sporadic Alzheimer's Disease in Chinese Group and Potential Functional
Importance for Novel Intronic Polymorphism., 11th Research Postgraduate
Symposium, 7 Dec. 2006. The |
|
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., Chu
L.W., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., Association of ABCA1 Gene with
Sporadic Alzheimer's Disease in Chinese Group and Potential Functional
Importance for Novel Intronic Polymorphism., 11th Research Postgraduate
Symposium, 7 Dec. 2006. The |
|
Researcher
: Liu C |
|
List of Research Outputs |
|
Liu
C., Xie L...X., Huang J., Liao F...L., Liu L., Goto S.
and Li M., Protective Effects of Chinese Medicine Salvianolic Acid B,
Astragaloside IV, and Daillyl Trisulfide on Endothelial Cells against damage
induced by H2O2., The 2nd International Conference of Cardiovascular Specialty
Committee. World federation of Chinese Medicine Societies Cordiovascular
Specialty Specialty Committee. Oct 21-22, 2006 |
|
Liu
C., Xie L...X., Huang J., Liao F...L., Liu L., Goto S.
and Li M., Protective effects of Salvianolic acid B, Astragaloside IV, and DT
on endothelial cells against damage induced by H2O2, The
4th Asian-Pacific Congress on Thrombosis and Hemostasis. September 21-23,
2006. |
|
Xie L...X., Liu C., Huang J., Liao F...L., Liu L., Goto S.
and Li M., Anti-apoptosis effects of Chinese herbal medicine Salvianolic Acid
B (Sal B) on rat Cerebral Microvascular Endothelial Cells., The 4th
Asia-Pacific Congress on Thrombosis and Hemostasis. September 21-23, 2006. |
|
Researcher
: Liu D |
|
List of Research Outputs |
|
Huang
J., Watt R.M., Wang J., Leong M.K., Liu D. and Danchin A.L.M., Visualizing becterial
proteomes., 14th International Molecular Medicine Tri-Conference. Feb
27-Mar 2 San Franciso, CA, |
|
Huen M...S...Y., Lu L., Liu D. and Huang J., Active transcription promotes single-stranded oligonucleotide mediated gene repair., Biochemiscal and Biophysical Research Communications. 2007, 353(1): 33-39. |
|
Huen M...S...Y., Li X., Lu L., Watt R.M., Liu D. and Huang J., The involvement of replication in single stranded oligonucleotide-mediated gene repair., Nucleic Acids Research. 2006, 34(21): 6183-6194. |
|
Watt R.M., Wang J., Leong M.K., Kung H...F., Cheah K.S.E., Liu D., Danchin A.L.M. and Huang J., Visualizing the proteome of Escherichia coli: an efficient and versatile method for labeling chromosomal coding DNA sequences (CDSs) with fluorescent protein genes., Nucleic Acids Research. 2007, 35(6): 1-11. |
|
Researcher
: Liu H |
|
List of Research Outputs |
|
Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chau C.H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4th Congress of FAONS, Nov13-Dec2, Hong Kong. 2006, 13. |
|
Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4th Congress of FAONS. 2006, 13. |
|
Liu H., Liu J., Chan C., Chau C.H., Chan Y.S. and Shum D.K.Y., Chondroitin sulfate moieties that are upregulated in Schwann cell-astrocyte encounters, Gordon research Conference on Proteoglycans July 9-14 Andover, New Hampshire, USA. 2006. |
|
Liu H. and Shum D.K.Y., Chondroitin sulfate proteoglycans in astrocyte-Schwann cell cocultures limit neurite extension and crossing of cellular boundaries, Neurosignals. 2006, 15: 126-126. |
|
Researcher
: Liu J |
|
List of Research Outputs |
|
Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chau C.H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4th Congress of FAONS, Nov13-Dec2, Hong Kong. 2006, 13. |
|
Liu H., Liu J., Chan C., Chau C.H., Chan Y.S. and Shum D.K.Y., Chondroitin sulfate moieties that are upregulated in Schwann cell-astrocyte encounters, Gordon research Conference on Proteoglycans July 9-14 Andover, New Hampshire, USA. 2006. |
|
Wang Y., Lam J.B.B., Liu J., Lam K.S.L., Cooper G.J.S. and Xu A., Adiponectin Plays Inhibitory Roles in the Proliferation and Tumor Development of Human MDA-MB-231 Breast Cancer Cells, 2nd Modern Drug Discovery & Development Summit. 2006. |
|
Wang Y., Lam J.B.B., Lam K.S.L., Liu J., Hoo R.L.C. and Xu A., Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. , Cancer Research. 2006, 66: 11462-70. |
|
Researcher
: Liu J |
|
List of Research Outputs |
|
Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chau C.H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4th Congress of FAONS, Nov13-Dec2, Hong Kong. 2006, 13. |
|
Liu H., Liu J., Chan C., Chau C.H., Chan Y.S. and Shum D.K.Y., Chondroitin sulfate moieties that are upregulated in Schwann cell-astrocyte encounters, Gordon research Conference on Proteoglycans July 9-14 Andover, New Hampshire, USA. 2006. |
|
Wang Y., Lam J.B.B., Liu J., Lam K.S.L., Cooper G.J.S. and Xu A., Adiponectin Plays Inhibitory Roles in the Proliferation and Tumor Development of Human MDA-MB-231 Breast Cancer Cells, 2nd Modern Drug Discovery & Development Summit. 2006. |
|
Wang Y., Lam J.B.B., Lam K.S.L., Liu J., Hoo R.L.C. and Xu A., Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. , Cancer Research. 2006, 66: 11462-70. |
|
Researcher
: Lo RLK |
|
List of Research Outputs |
|
Ho M...S., Tsang K.Y., Lo R.L.K., Susic M., Makitie O.,
Chan T...W., Ng V.C.W., Sillence
D...O., Boot-Handford R...P., Gibson G., Cheung K...M., Cole W...G., Cheah K.S.E. and Chan D., COL |
|
Lo R.L.K., ER-Stress Signaling And Chondrocyte Differentiation in Mice, M.Phil Thesis. 2006. |
|
Researcher
: Lu L |
|
List of Research Outputs |
|
Huen M...S...Y., Lu L., Liu D. and Huang J., Active transcription promotes single-stranded oligonucleotide mediated gene repair., Biochemiscal and Biophysical Research Communications. 2007, 353(1): 33-39. |
|
Huen M...S...Y., Li X., Lu L., Watt R.M., Liu D. and Huang J., The involvement of replication in single stranded oligonucleotide-mediated gene repair., Nucleic Acids Research. 2006, 34(21): 6183-6194. |
|
Lu L., Investigations into the feasibility of single-stranded oligonucleotide-mediated targeted gene repair in mammalian cells., PhD Thesis. 2006. |
|
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., Law M.L., Tsang W.H., Tam P.K.H., Lui V.C.H. and Sham M.H., Study of the Impact of Sox10
Mutation on the Development of Enteric Nervous System in a Mutant Mouse Model
Generated by Gene Targeting., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
|
Researcher
: Melhado IG |
|
List of Research Outputs |
|
Melhado I.G., Cheah K.S.E., Chan D., Tsang K.Y., Chan W.C.W. and Wang C., Towards an understanding of global gene expression changes in hypertrophic chondrocytes undergoing ER stress, Gordon Research Conference in Cartilage Biology. 2007. |
|
Tsang K.Y., Chan D., Cheslett D., Chan W.C.W., So C...L., Melhado I.G., Chan W.Y., Kwan K...M., Hunziker E...B., Yamada Y., Bateman J...F., Cheung K.M.C. and Cheah K.S.E., Surviving ER Stress is Coupled to Altered Chondrocyte Differentiation and Function., PLoS Biology. 2007, 5(3): 44. |
|
Researcher
: Ng MH |
|
List of Research Outputs |
|
Kok K.H., Ng M.H., Ching Y.P. and Jin D., Human TRBP and PACT directly interact with each other and associated with Dicer to facilitate the production of small interfering RNA , Journal of Biological Chemistry. 2007, 282: 17649-17657. |
|
Researcher
: Ng VCW |
|
List of Research Outputs |
|
Chan W.C.W., Ng V.C.W., Wang C., Tsang K.Y., Cheah K.S.E. and Chan D., ER-stress signaling in the pathogenesis of Schmid metaphyseal chondrodysplasia , Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 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., 11th Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Ho M...S., Tsang K.Y., Lo R.L.K., Susic M., Makitie O., Chan
T...W., Ng V.C.W., Sillence
D...O., Boot-Handford R...P., Gibson G., Cheung K...M., Cole W...G., Cheah K.S.E. and Chan D., COL |
|
Researcher
: Ni Y |
|
List of Research Outputs |
|
Ni
Y., Liu L...X., Qu J...L., Niu H...B., Li G.
and Huang J., Axonal APP Interacts
with BACE in Anterograde Transport-Dependent Manner., 2007 World Congress
on Ageing and Dementia in Chinese Communities. March 7-10, 2007, Hong Kong
SAR, |
|
Researcher
: Pelling AL |
|
List of Research Outputs |
|
Pelling
A.L., Leung
K.K.H., Tang A.S.P. and Cheah K.S.E., Faculty Outstanding
Research Output Award, Faculty of Medicine, The University of |
|
Researcher
: Poon SCS |
|
List of Research Outputs |
|
Song Y., Cheung K.M.C., Ho D.W.H., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Yee A.F.Y., Poon S.C.S., 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 to lumbar disc degeneration in Chinese and Japanese., Gordon Research Conference on Cartilage Biology and Pathology, March 4-9, 2007, Ventura, CA, USA. 2007. |
|
Researcher
: Sae-Pang JJ |
|
List of Research Outputs |
|
Chan K.T., Sae-Pang J.J., Tsang S.L., Tsang W.H., Kahmeyer-Gabbe M. and Sham M.H., A Hoxb3Mouse Mutant with Abnormal Thoracic Body Wall Development , Mouse Molecular Genetics August 30-September 3, 2006 Cold Spring Harbour, New York. 2006. |
|
Sae-Pang J.J., Analysis Of Multiple Cardiac Abnormalities In A Hoxb Mouse Mutant, Ph.D. Thesis. 2007. |
|
Sae-Pang
J.J., Cardiac developmental defects in a Hoxb
mouse mutant Hoxb3lacZ, Best Poster Award, MGH-HKU-Nature |
|
Sae-Pang J.J., Chan K.T., Tsang S.L., Tsang W...H. and Sham M.H., Cardiac developmental defects in a Hoxb mouse mutant Hoxb3lacZ, MGH-HKU-Nature China Forum, Hong Kong, March 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., Li H., Xu R. and Sham M.H., Vasostatin gene therapy suppressed lung tumor growth and metastasis using adeno-associated virus pseudotype 5 vector, MGH-HKU-Nature China Forum, Hong Kong. March 2007. |
|
Chan K.T., Sae-Pang J.J., Tsang S.L., Tsang W.H., Kahmeyer-Gabbe M. and Sham M.H., A Hoxb3Mouse Mutant with Abnormal Thoracic Body Wall Development , Mouse Molecular Genetics August 30-September 3, 2006 Cold Spring Harbour, New York. 2006. |
|
Chee
D.M.C., Law M.L., Tsang W.H., Tam P.K.H., Lui V.C.H. and Sham M.H., Study of the Impact of
Sox10 Mutation on the Development of Enteric Nervous System in a Mutant Mouse
Model Generated by Gene Targeting., 11th Research Postgraduate Symposium,
7 Dec. 2006. The |
|
Ko K.H., Lam Q.L.K., Zhang M., Wong C.K.Y., Lo K.C., Kahmeyer-Gabbe M., Tsang W.H., Tsang S.L., Chan L.C., Sham M.H. and Lu L., Hoxb3 deficiency impairs B lymphopoiesis in mouse bone marrow, Experimental Hematology. 2007, 35(3): 465-75. |
|
Ngan E.S.W., Poon H.C., Sham M.H., Tam P.K.H. and Lui V.C.H., Aberrant KLF4 expression and BMP signaling cause proliferation defect in PTC1-/- neural crest cells (The Best Poster Presentation at the Forum), MGH-HKU-Nature China Forum, Hong Kong, 5-6 March 2007. |
|
Ngan E.S.W., Poon H.C., Sham M.H., Hui C.C., Wainwright B., Tam P.K.H. and Lui V.C.H., Aberrant Kruppel-like factor 4 expression causes proliferation defect in Patched1-/- neural crest cells, The 5th Annual Meeting of the International Society for Stem Cell Research, Cairns, Queensland, Australia, 17-20 June 2007. |
|
Ngan E.S.W., Lee K.Y., Sit Y.L.F., Poon H.C., Chan J.K.Y., Sham M.H., Lui V.C.H. and Tam P.K.H., Prokineticin-1 modulates proliferation and differentiation of enteric neural crest cells, Biochimica et Biophysica Acta. 2007, 1773(4): 536-545. |
|
Ngan
E.S.W., Lee K.Y., Sit F.Y.L., Chan J.K.Y., Sham M.H., Lui V.C.H. and Tam P.K.H., Roles of Prokineticin |
|
Ngan E.S.W., Poon H.C., Sham M.H., Hui C.C., Brandon W., Tam P.K.H. and Lui V.C.H., The Best Poster Presentation, MGH-HKU-Nature China Forum . 2007. |
|
Sae-Pang J.J., Chan K.T., Tsang S.L., Tsang W...H. and Sham M.H., Cardiac developmental defects in a Hoxb mouse mutant Hoxb3lacZ, MGH-HKU-Nature China Forum, Hong Kong, March 2007. |
|
Sham M.H., Cheng M.H., Chao Z., Tsang S.L., Chan C.P., Choy R...K...W. and Song Y., Mapping the locus for a novel cataract mouse mutant with microphthalmia and closed eyelid., HUGO 12th Human Genome Meeting, Montreal, Canada. May, 2007. |
|
Tsang
H.M., Kong C.T., Sham M.H. and Chan L.C., Analysis of Mll-Een Fusion
Gene in Mouse Leukemic Model, Keystone Symposium - Mouse Models at the
Frontiers of Cancer Discovery. Whistler Resort, Whistler, |
|
Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Lu L...W., Chan L.C. and Sham M.H., Hoxb3 mutation leads to interleukin-6 dependent plasmacytoma., The 19th Meeting of the European Association for Cancer Research, Budapest, Hungary. July 2006. |
|
Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Chan L.C., Lu L...W. and Sham M.H., The impact of Hoxb3 mutation on plasmacytoma., The 36th Annual Meeting of the Japanese Society for Immunology, Osaka, Japan. December, 2006. |
|
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 |
|
Kao
P.Y.P., Sham P.C., Chan D., Cheung K.M.C. and Song Y., Investigating Epistasis in
Degenerative Disc Disease., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
|
Researcher
: Shea GKH |
|
List of Research Outputs |
|
Shea G.K.H., Towards the Use of Stem-cell-derived Schwann Cells to Bridge
Injured Nerves , 11th Research Postgraduate Symposium, 7 Dec. 2006. The |
|
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 |
|
Chan
C.H., Ip M.S.M. and Shum D.K.Y., Targeting heparan
sulfate/syndecan |
|
Chan
C.H., Kwok A.W.S., Chan Y.S., Li X. and Shum D.K.Y., Upregulation of nitrated
chondroitin sulfate proteoglycans in reactive astrocytes and cerebrospinal
fluid of patients with amyotrophic lateral sclerosis, Proceedings of the
4th Congress of FAONS, Nov 30 - Dec 2, |
|
Chan Y.S., Lai C.H. and Shum D.K.Y., Spatial coding capacity of central otolith neurons. , Exp Brain Res. 2006, 173(2): 205-214. |
|
Chen L.W., Zhang J.P., Shum D.K.Y. and Chan Y.S., Localization of NGF, NT3 and GDNF in nestin-expressing reactive astrocytes in the caudate-putamen of MPTP-treated C57/BL mice, Journal of Comparative Neurology. 2006, 497(6): 898-909. |
|
Gohel M...D., Shum D.K.Y. and Tam P...C., Electrophoretic separation and characterization of urinary glycosaminoglycans and their roles in urolithiasis., Carbohydr Res.. 2007, 342(1): 79-86. |
|
Kwok J.C.F., Lau J.W.K., Ng K.Y., Shum D.K.Y. and Chan Y.S., Chondroitin sulfates enriched in the developing rat hindbrain restrict commissural projections of vestibular neurons, Neurosignals. 2006, 15: 123-123. |
|
Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chau C.H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4th Congress of FAONS, Nov13-Dec2, Hong Kong. 2006, 13. |
|
Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4th Congress of FAONS. 2006, 13. |
|
Lai C.H., Tse Y.C., Shum D.K.Y. and Chan Y.S., Toward maturation of the vestibular system: neural circuits and neuronal properties, Neuroembryology and Aging. 2006, 3: 162-170. |
|
Lau J.W.K., Kwok J.C.F., Ng T...K., Chan Y.S. and Shum D.K.Y., Developing vestibular neurons display differential commissural projection patterns with digestion of chondroitin sulfates, Proceedings of the 4th Congress of FAONS Nov 30 - Dec 2, Hong Kong. 2006, 25. |
|
Liu H., Liu J., Chan C., Chau C.H., Chan Y.S. and Shum D.K.Y., Chondroitin sulfate moieties that are upregulated in Schwann cell-astrocyte encounters, Gordon research Conference on Proteoglycans July 9-14 Andover, New Hampshire, USA. 2006. |
|
Liu H. and Shum D.K.Y., Chondroitin sulfate proteoglycans in astrocyte-Schwann cell cocultures limit neurite extension and crossing of cellular boundaries, Neurosignals. 2006, 15: 126-126. |
|
Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Change in the composition of perineuronal nets of central vestibular neurons following unilateral labyrinthectomy, Congress of FAONS. 2006, 100. |
|
Ma
C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in Perineuronal Nets
within the Rat Vestibular Nuclei during Postnatal Development and in Injury.,
11th Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in perineuronal nets within the rat vestibular nuclei during postnatal development and in injury, Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 12. |
|
Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in perineuronal nets within the rat vestibular nuclei during postnatal development and in injury, Society for Neuroscience (USA) Oct 14-18 Altanta, GA, USA. 2006, 550.12. |
|
Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Modifications in perineuronal nets of rat vestibular nuclear neurons after unilateral labyrinthectomy, The 2nd Int'l Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4 Hong Kong. 2007, P41. |
|
Ma
C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Modifications in perineuronal
nets within the rat vestibular nuclei during postnatal development, Proceedings
of the 29th Annual Meeting of |
|
Ma
C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Proceedings of the 4th
Congress of FAONS, Nov. 30 - Dec. 2 |
|
Shum
D.K.Y., Growth inhibitory & facilitatory
aspects of chondroitin sulfates in vivo and in vitro., Stem Cell Workshop.
The |
|
Sun X., Xia Q., Lai C...H., Shum D.K.Y., Chan Y...S. and He J., Corticofugal modulation of acoustically induced Fos expression in the rat auditory pathway., J Comp Neutrol. 2007, 501(4): 509-25. |
|
Sun X., Xia Q., Lai C.H., Shum D.K.Y., Chan Y.S. and He J., Corticofugal modulation on acoustically induced Fos expression in the rat auditory pathway, J. Comparative Neurology. 2007, 501: 509-525. |
|
Tam
K.W., Li R.A., Chan Y.S. and Shum D.K.Y., Chondroitinases ABC I
and II from Proteus Vulgaris for Therapuetic Use: Cloning and
Characterization., 11th Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Tam
K.W., Li R...A., Chan Y.S. and Shum D.K.Y., Recombinant expression
and characterization of chondroitinse ABC I and II, The 2nd Int'l
Symposium on Healthy Aging: Meeting the Challenges of an Aging Population,
March 3-4 |
|
Wang
M., Shum D.K.Y., |
|
Wang M., Shum D.K.Y., |
|
Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of heparanase in the normal versus injured spinal cord of adult rats, Soc. Neuroscience Abstract (U.S.A.). 2006, 720: 12. |
|
Zhang
Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of
heparanase in the normal versus injured spinal cord of adult rats, Society
for Neuroscience ( |
|
Zhang
Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of
heparanase in the normal versus injured spinal cord of adult rats, Society
for Neuroscience Abstracts ( |
|
Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Expression patterns of heparanase in normal and injured rat spinal cord, Proceedings of the 4th Congress of FAONS. 2006, 67. |
|
Zhang Y., Yeung M.N., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats, J. Comparative Neurology. 2006, 494: 345-357. |
|
Zhang Y., Chan Y.S. and Shum D.K.Y., Molecular cloning characterization and purification of rat pro- and mature heparanase, The 2nd Int'l Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4 Hong Kong. 2007, P11. |
|
Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Proceedings of the 4th Congress of FAONS, Proceedings of the 4th Congress of FAONS. 2006, 67. |
|
Researcher
: Shum KT |
|
List of Research Outputs |
|
Shum
K.T., Leung
C.M., Wong L.Y., Chan C.S.L. and Tanner J.A., New Approaches for
Therapeutic Aptamer Selection and Delivery, MGH-HKU-Nature |
|
Researcher
: Siu KL |
|
List of Research Outputs |
|
Chan C.P., Siu K.L., Chin K.T., Yuen K.Y., Zheng B. and Jin D., Modulation of the unfolded protein response by severe acute respiratory syndrome coronavirus spike protein., Journal of Virology. 2006, 80: 9279-9287. |
|
Siu Y.T., Chin K.T., Siu K.L., Choy E.Y.W., Jeang K.T. and Jin D., TORC1 and TORC2 coactivators are required for Tax activation of the human T-cell leukemia virus type 1 long terminal repeats., Journal of Virology . 2006, 80: 7052-7059. |
|
Tang
V.H.M., Siu K.L. and Jin D., Peroxiredoxin-null Yeast Cells
are Hypersensitive to DNA-damaging Agents., 11th Research Postgraduate
Symposium, 7 Dec. 2006. The |
|
List of Research Outputs |
|
Siu Y.T., Chin K.T., Siu K.L., Choy E.Y.W., Jeang K.T. and Jin D., TORC1 and TORC2 coactivators are required for Tax activation of the human T-cell leukemia virus type 1 long terminal repeats., Journal of Virology . 2006, 80: 7052-7059. |
|
Siu Y.T. and Jin D., Tax-induced recruitment of TORC family coactivators is required for transcriptional activation of HTLV-I LTR (Young Scientists Award-winning presentation), 13th International Conference on Human Retrovirology: HTLV and Related Viruses. 2007. |
|
Siu Y.T. and Jin D., Tax-induced recruitment of TORC family coactivators is required for transcriptional activation of HTLV-I LTR, AIDS Research and Human Retroviruses. Mary Ann Liebert, Inc., 2007, 23: 646. |
|
Siu Y.T., Young Scientists Award, for the excellence of the work presented in title of "Tax-induced recruitment of TORC family coactivators is required for transcriptional activation of HTLV-1 LTR", In: Prof. Toshiki Watanabe, Organizing Chair of HTLV2007, Organizing Committee, The 13th International Conference on Human Retrovirology: HTLV and Related Viruses (HTLV2007, Japan). 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 |
|
Cai J., Woo P.C.Y., Lau S.K.P., Smith D.K. and Yuen K.Y., Accelerated evolutionary rate may be responsible for the emergence of lineage-specific genes in ascomycota., Journal of molecular evolution. 2006, 63(1): 1-11. |
|
Cheung W.M.W., Jin L., Smith D.K., Cheung P.T., Kwan E.Y.W., Low L.C.K. and Kung A.W.C., A family with osteoporosis pseudoglioma syndrome due to compound heterozygosity of two novel mutations in the LRP5 gene, Bone. 2006, 39: 470-6. |
|
Du L., Wu S., Liew A.W.C., Smith D.K. and Yan H., Parametric
spectral analysis of malaria gene expression time series data, In: Berthold
MR, Glen R and Fisher I, Computational Life Science II, Lecturer Notes in
Computer Science . |
|
Li
H.Y., Lum C.T., Sun R.W.Y., Ng S.M., Smith D.K., Yiu S.M., Che C.M. and Lin M.C., Genome-Wide Study Reveals the
Signaling Pathways Modulated by Gold |
|
Liew A...W., Xian J., Wu S., Smith D.K. and Yan H., Spectral estimation in unevenly sampled space of periodically expressed microarray time series data., BMC Bioinformatics. 2007, 8: 137. |
|
Tang S.M., Zhao Y., Smith D.K. and Epstein R., Intron length and accelerated 3' gene evolution., Genomics. 2006, 88: 682-89. |
|
Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD: Integrated Cartilage Gene Database for genetic study of cartilage, BMC Genetics . 2007, 8: 4. |
|
Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD:The Integrated Cartilage Gene Database., The Integrated Cartilage Gene Database. 2007. |
|
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, Cheah KSE, Sham PC |
|
Department: |
Genome Research Centre |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
|
Start Date: |
01/2006 |
|
Abstract: |
|
To perform a genome-wide scan using mouse
microsatellite markers to map the modifer locus to within a |
|
List of Research Outputs |
|
Au W.Y., Lam V.M.S., Pang A.W.K., Lee W.M., Chan L.C., Song Y., Ma E.S.K. and Kwong Y.L., Glucose-6-phosphate dehydrogenase deficiency in female octogenarians, nanogenarians, and centenarians, The Journals of Gerontology Series A: Biological Sciences and Medical Sciences . 2006, 61(10): 1086-1089. |
|
Chan D., Song Y., Sham P.C. and Cheung K.M.C., Genetics of disc degeneration, Eur Spine J. 2006, 15 Suppl 15: 317-25. |
|
Cheung
K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S...P., Cheong
J...C...Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan
degradation pathway act synergistically to predispose to degenerative disc
disease., International Society for the Study of the Lumbar Spine. 34th
annual Meeting, June 10-14, 2007 |
|
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. |
|
Fong C.Y., Kwok H.H., Song Y., Cheng T.S., Ho W.L., Chu A.C.Y., Kung M.H.W., Chan K.H., Mak W., Cheung R.T.F., Ramsden D.B. and Ho S.L., Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation., Amyotrophic Lateral Sclerosis. 2006, 7(3): 142-149. |
|
Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S...P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on Familial Early-Onset Degenerative Disc Disease (DDD)., ABS#apbc056 Jan14-17. 2007. |
|
Kao
P.Y.P., Sham P.C., Chan D., Cheung K.M.C. and Song Y., Investigating Epistasis in
Degenerative Disc Disease., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
|
Kao P.Y.P., Chan D., Cheung K.M.C., Cheah K.S.E., Sham P.C. and Song Y., Investigating Epistasis in Degenerative Disc Disease., ABS#apbc101 Jan 14-17, 2007. |
|
Kong E...K., Chong W...P., Wong W...H.,
Lau C...S., Chan T...M., Ng P...K., Song
Y., Mak W. and Lau Y...L., p21 gene polymorphisms in systemic lupus
erythematosus., Rheumatology ( |
|
Lee
B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tang L.F., Song Y. and Tanner J.A., Functional Study of
Cerberus-like and Noggin Proteins: toward a Biochemical Understanding of BMP
Antagonists in Skeletal Disorders, 11th Research Postgraduate Symposium, 7
Dec. 2006. The |
|
Li Y.,
Chu L.W., Cheung B.M.Y., Leung Y.H., Yik P.Y., Jin D. and Song Y., Association of ABCA1 Gene
with Sporadic Alzheimer's Disease in Chinese Group and Potential Functional
Importance for Novel Intronic Polymorphism., 11th Research Postgraduate
Symposium, 7 Dec. 2006. The |
|
Ong K.L., Wong L.Y.F., Man Y.B., Leung Y., Song Y., Lam K.S.L. and Cheung B.M.Y., Haplotypes in the urotensin II gene and urotensin II receptor gene are associated with insulin resistance and impaired glucose tolerance., Peptides. 2006, 27(7): 1659-67. |
|
Rogaeva E., Meng Y., Lee J.H., Gu Y., Kawarai T., Zou F., Katayama T., Baldwin C.T., Cheng R., Hasegawa H., Chen F., Shibata N., Lunetta K.L., Song Y., Fraser P.E., Schmitt-Ulms G., Younkin S., Mayeux R., Farrer L.A. and St George-Hyslop P., The sortilin-related receptor SORL1 is genetically associated with Alzheimer’s Disease, Nature Genetics . 2007, 39: 168-177. |
|
Sham M.H., Cheng M.H., Chao Z., Tsang S.L., Chan C.P., Choy R...K...W. and Song Y., Mapping the locus for a novel cataract mouse mutant with microphthalmia and closed eyelid., HUGO 12th Human Genome Meeting, Montreal, Canada. May, 2007. |
|
Song Y., Cheung K.M.C., Ho D.W.H., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Yee A.F.Y., Poon S.C.S., 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 to lumbar disc degeneration in Chinese and Japanese., Gordon Research Conference on Cartilage Biology and Pathology, March 4-9, 2007, Ventura, CA, USA. 2007. |
|
Song
Y., Linkage Analysis of Familial Early-onset
Degenerative Disc Disease (DDD)., HKU-University of |
|
Song
Y., Cheung
K.M.C., Fan B., Karppinen J., Yip
S...P., Leong J...C...Y., Luk K.D.K.,
Ott J., Cheah K.S.E., Sham P.C. and Chan D., SNP-SNP Interaction in
Intervertebral Disc Disease with Genes in the Aggrecan Degradation Pathway, The
8th International Meeting on Human Genome Variation and Complex Genome
Analysis. Le Meridien Cyberport Hotel and Convention Centre, Hong Kong SAR, |
|
Tai A...L., Mak W., Ng P...K., Chua
D...T., Ng M...Y., Fu L., |
|
Tang L.F., Tang A.Y.B., Cheah K.S.E. and Song Y., Identification of a genetic modifier of CHD in Type IIA procollagen deficient mutant mice., ICSB 2006, Oct9-13, 2006, Yokohama, Japan. 2006. |
|
Tang
L.F., Tang A.Y.B., Cheah K.S.E. and Song Y., Identification of a genetic
modifier of CHD in Type IIA procollagen deficient mutant mice, Travel
Award. The 7th International Conferernce on Systems Biology. |
|
Tang
L.F., Cheah K.S.E. and Song Y., Mapping of a Genetic
Modifier of Congenital Heart Defect in Type IIA Procollagen Deficient Mice, 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Tang
L.F., Cheah K.S.E. and Song Y., Mapping of genetic modifier
of congenital heart defects in type IIA procollagen deficient mice., APBC2007,
|
|
Virtanen I...M., Song Y., Cheung K.M.C., Ala-Kokko L., Karppinen J., Ho D.W.H., Luk K.D.K., Yip S...P., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Chan D., Phenotypic and Population Differences in the Association between CILP and Lumbar Disc Disease., Journal of Medical Genetics. 2007, 44(4): 285-8. |
|
Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD: Integrated Cartilage Gene Database for genetic study of cartilage, BMC Genetics . 2007, 8: 4. |
|
Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD:The Integrated Cartilage Gene Database., The Integrated Cartilage Gene Database. 2007. |
|
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 |
|
Szeto
Y.Y., Role of Sox |
|
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 |
|
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 |
|
Chee
D.M.C., Law M.L., Tsang W.H., Tam P.K.H., Lui V.C.H. and Sham M.H., Study of the Impact of Sox10
Mutation on the Development of Enteric Nervous System in a Mutant Mouse Model
Generated by Gene Targeting., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
|
Researcher
: Tang ASP |
|
List of Research Outputs |
|
Pelling
A.L., Leung K.K.H., Tang A.S.P. and Cheah K.S.E., Faculty Outstanding
Research Output Award, Faculty of Medicine, The University of |
|
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. |
|
Tang L.F., Tang A.Y.B., Cheah K.S.E. and Song Y., Identification of a genetic modifier of CHD in Type IIA procollagen deficient mutant mice., ICSB 2006, Oct9-13, 2006, Yokohama, Japan. 2006. |
|
Tang
L.F., Tang A.Y.B., Cheah K.S.E. and Song Y., Identification of a genetic
modifier of CHD in Type IIA procollagen deficient mutant mice, Travel
Award. The 7th International Conferernce on Systems Biology. |
|
Researcher
: Tang LF |
|
List of Research Outputs |
|
Lee
B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tang L.F., Song Y. and Tanner J.A., Functional Study of
Cerberus-like and Noggin Proteins: toward a Biochemical Understanding of BMP
Antagonists in Skeletal Disorders, 11th Research Postgraduate Symposium, 7
Dec. 2006. The |
|
Tang L.F., Tang A.Y.B., Cheah K.S.E. and Song Y., Identification of a genetic modifier of CHD in Type IIA procollagen deficient mutant mice., ICSB 2006, Oct9-13, 2006, Yokohama, Japan. 2006. |
|
Tang L.F., Tang A.Y.B., Cheah K.S.E. and Song Y., Identification of a genetic
modifier of CHD in Type IIA procollagen deficient mutant mice, Travel
Award. The 7th International Conferernce on Systems Biology. |
|
Tang
L.F., Cheah
K.S.E. and Song Y., Mapping of a
Genetic Modifier of Congenital Heart Defect in Type IIA Procollagen Deficient
Mice, 11th Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Tang
L.F., Cheah
K.S.E. and Song Y., Mapping of
genetic modifier of congenital heart defects in type IIA procollagen
deficient mice., APBC2007, |
|
Researcher
: Tang LF |
|
List of Research Outputs |
|
Lee
B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tang L.F., Song Y. and Tanner J.A., Functional Study of
Cerberus-like and Noggin Proteins: toward a Biochemical Understanding of BMP
Antagonists in Skeletal Disorders, 11th Research Postgraduate Symposium, 7
Dec. 2006. The |
|
Tang L.F., Tang A.Y.B., Cheah K.S.E. and Song Y., Identification of a genetic modifier of CHD in Type IIA procollagen deficient mutant mice., ICSB 2006, Oct9-13, 2006, Yokohama, Japan. 2006. |
|
Tang L.F., Tang A.Y.B., Cheah K.S.E. and Song Y., Identification of a genetic
modifier of CHD in Type IIA procollagen deficient mutant mice, Travel
Award. The 7th International Conferernce on Systems Biology. |
|
Tang
L.F., Cheah
K.S.E. and Song Y., Mapping of a
Genetic Modifier of Congenital Heart Defect in Type IIA Procollagen Deficient
Mice, 11th Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Tang
L.F., Cheah
K.S.E. and Song Y., Mapping of
genetic modifier of congenital heart defects in type IIA procollagen
deficient mice., APBC2007, |
|
Researcher
: Tang VHM |
|
List of Research Outputs |
|
Tang
V.H.M., Siu
K.L. and Jin D.,
Peroxiredoxin-null Yeast Cells are Hypersensitive to DNA-damaging Agents., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
|
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 |
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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) |
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Start Date: |
11/2006 |
|
Abstract: |
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(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 |
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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: |
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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. |
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List of Research Outputs |
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Chan C.S.L., Leung C.M., Wong L.Y., Chan D., Cheah K.S.E. and Tanner J.A., Purification and Identification of Sclerostin Interacting Partners: Steps towards Osteoporosis Therapy with Aptamer-based Inhibitors, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU . 2006. |
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Chan W.L., Chan D., Lee S., Cheah K.S.E. and Tanner J.A., A Proteomic Approach To Study The Molecular Mechanisms Of The Unfolded Protein Response In The Endoplasmic Reticulum Of Chondrocytes, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU . 2006. |
|
Choi
M.Y., Chan C.C.Y., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Molecular Mechanism of
Disease for Spondyloepiphyseal Dysplasia Tarda-Effect of Mutations on sedlin
structure and Function., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
|
Ge R., Sun X., Gu Q., Watt R.M., Tanner J.A., Wong B...C...Y., Xia H...H., Huang J., He Q. and Sun H., A Proteomic Approach for Identification of Bismuth-binding Proteins in Helicobacter pylori., Journal of Biological Inorganic Chemistry. 2007, 12: 831-842. |
|
Lee
B.B.C., Chan C.S.L., Chan D., Cheah K.S.E., Tang L.F., Song Y. and Tanner J.A., Functional Study of
Cerberus-like and Noggin Proteins: toward a Biochemical Understanding of BMP
Antagonists in Skeletal Disorders, 11th Research Postgraduate Symposium, 7
Dec. 2006. The |
|
Melnik S., Wright M., Tanner J.A., Tsintsadze T., Tsintsadze V., Miller A...D. and Lozovaya N., Diadenosine Polyphosphate Analog Controls Postsynaptic Excitation in CA3-CA1 Synapses via a Nitric Oxide-Dependent Mechanism., J Pharmacol Exp Ther. 2006, 318: 579-588. |
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Melnik S.I., Wright M., Tanner J.A., Tsintadze T., Tsintadze V.P., Miller A.D. and Lozova N.O., Diadenosine polyphosphate analogue modulates signal transduction in hippocampal slices. , Fiziol Zh. 2006, 52: 9-12. |
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Miller A.D., Wright M., Tanner J.A. and Lozovaya N.O., New Uses of Dinucleotide Polyphosphate Derivatives, European Patent. 2006, WO2006082397. |
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Shum
K.T., Leung C.M., Wong L.Y., Chan C.S.L. and Tanner J.A., New Approaches for
Therapeutic Aptamer Selection and Delivery, MGH-HKU-Nature |
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Tanner
J.A., WTO TRIPS and its Effect on the Supply
and Development of Medicines in |
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Wright M., Boonyalai N., Tanner J.A., Hindley A...D. and Miller A...D., The duality of LysU, a catalyst for both Ap(4)A and Ap(3)A formation., FEBS J. 2006, 273: 3534-3544. |
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Yang N., Tanner J.A., Huang J., Zheng B...J. and Sun H...Z.,
Inhibition of SARS Coronavirus by Bismuth Compounds., The 3rdAsian
Biological Inorganic Chemistry Conference(AsBIC-3) 31Oct-3 Nov. 2006, |
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Yang N., Tanner J.A., Huang J., Zheng B. and Sun H., Inhibition of SARS Coronavirus by Bismuth Compounds, 3rd Asian Biological Inorganic Chemistry Conference, Nanjing, P.R. China, October 30- November 3. 2006. |
|
Researcher
: Tong HK |
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List of Research Outputs |
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Tong
H.K., Functional regulation of the Forkhead |
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List of Research Outputs |
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Chan W.C.W., Ng V.C.W., Wang C., Tsang K.Y., Cheah K.S.E. and Chan D., ER-stress signaling in the pathogenesis of Schmid metaphyseal chondrodysplasia , Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 2007. |
|
Chik
H.H.Y., Tsang K.Y., Cheng Y.W., Chan W.C.W., Cheah K.S.E. and Chan D., Genomic Analysis of Increased
Osteoblast Activity in a Mouse with generalized Hyperostosis., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Ho M...S., Tsang K.Y., Lo R.L.K., Susic M., Makitie O., Chan
T...W., Ng V.C.W., Sillence D...O.,
Boot-Handford R...P., Gibson G., Cheung K...M., Cole W...G., Cheah K.S.E. and Chan D., COL |
|
Melhado I.G., Cheah K.S.E., Chan D., Tsang K.Y., Chan W.C.W. and Wang C., Towards an understanding of global gene expression changes in hypertrophic chondrocytes undergoing ER stress, Gordon Research Conference in Cartilage Biology. 2007. |
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Tsang K.Y., Chan D., Partanen J. and Cheah K.S.E., Fibroblast growth factor receptor 1 (FGFR1) regulates terminal differentiation of hypertrophic chondrocytes, Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 2007. |
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Tsang K.Y., Chan D., Cheslett D., Chan W.C.W., So C...L., Melhado I.G., Chan W.Y., Kwan K...M., Hunziker E...B., Yamada Y., Bateman J...F., Cheung K.M.C. and Cheah K.S.E., Surviving ER Stress is Coupled to Altered Chondrocyte Differentiation and Function., PLoS Biology. 2007, 5(3): 44. |
|
Researcher
: Tsang SL |
|
List of Research Outputs |
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Chan K.T., Sae-Pang J.J., Tsang S.L., Tsang W.H., Kahmeyer-Gabbe M. and Sham M.H., A Hoxb3Mouse Mutant with Abnormal Thoracic Body Wall Development , Mouse Molecular Genetics August 30-September 3, 2006 Cold Spring Harbour, New York. 2006. |
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Ko K.H., Lam Q.L.K., Zhang M., Wong C.K.Y., Lo K.C., Kahmeyer-Gabbe M., Tsang W.H., Tsang S.L., Chan L.C., Sham M.H. and Lu L., Hoxb3 deficiency impairs B lymphopoiesis in mouse bone marrow, Experimental Hematology. 2007, 35(3): 465-75. |
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Sae-Pang J.J., Chan K.T., Tsang S.L., Tsang W...H. and Sham M.H., Cardiac developmental defects in a Hoxb mouse mutant Hoxb3lacZ, MGH-HKU-Nature China Forum, Hong Kong, March 2007. |
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Sham M.H., Cheng M.H., Chao Z., Tsang S.L., Chan C.P., Choy R...K...W. and Song Y., Mapping the locus for a novel cataract mouse mutant with microphthalmia and closed eyelid., HUGO 12th Human Genome Meeting, Montreal, Canada. May, 2007. |
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Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Lu L...W., Chan L.C. and Sham M.H., Hoxb3 mutation leads to interleukin-6 dependent plasmacytoma., The 19th Meeting of the European Association for Cancer Research, Budapest, Hungary. July 2006. |
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Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Chan L.C., Lu L...W. and Sham M.H., The impact of Hoxb3 mutation on plasmacytoma., The 36th Annual Meeting of the Japanese Society for Immunology, Osaka, Japan. December, 2006. |
|
Researcher
: Tsang SW |
|
List of Research Outputs |
|
Tsang
S.W. and Yao
K.M., Involvement of PDZD |
|
Tsang
S.W., Leung P...S., Cheah K.S.E., Thomas M...K. and Yao K.M., Involvement of PDZD |
|
Researcher
: Tsang WH |
|
List of Research Outputs |
|
Chan K.T., Sae-Pang J.J., Tsang S.L., Tsang W.H., Kahmeyer-Gabbe M. and Sham M.H., A Hoxb3Mouse Mutant with Abnormal Thoracic Body Wall Development , Mouse Molecular Genetics August 30-September 3, 2006 Cold Spring Harbour, New York. 2006. |
|
Chee
D.M.C., Law M.L., Tsang W.H., Tam P.K.H., Lui V.C.H. and Sham M.H., Study of the Impact of Sox10
Mutation on the Development of Enteric Nervous System in a Mutant Mouse Model
Generated by Gene Targeting., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
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Ko K.H., Lam Q.L.K., Zhang M., Wong C.K.Y., Lo K.C., Kahmeyer-Gabbe M., Tsang W.H., Tsang S.L., Chan L.C., Sham M.H. and Lu L., Hoxb3 deficiency impairs B lymphopoiesis in mouse bone marrow, Experimental Hematology. 2007, 35(3): 465-75. |
|
Researcher
: Tsang WH |
|
List of Research Outputs |
|
Chan K.T., Sae-Pang J.J., Tsang S.L., Tsang W.H., Kahmeyer-Gabbe M. and Sham M.H., A Hoxb3Mouse Mutant with Abnormal Thoracic Body Wall Development , Mouse Molecular Genetics August 30-September 3, 2006 Cold Spring Harbour, New York. 2006. |
|
Chee
D.M.C., Law M.L., Tsang W.H., Tam P.K.H., Lui V.C.H. and Sham M.H., Study of the Impact of Sox10
Mutation on the Development of Enteric Nervous System in a Mutant Mouse Model
Generated by Gene Targeting., 11th Research Postgraduate Symposium, 7 Dec.
2006. The |
|
Ko K.H., Lam Q.L.K., Zhang M., Wong C.K.Y., Lo K.C., Kahmeyer-Gabbe M., Tsang W.H., Tsang S.L., Chan L.C., Sham M.H. and Lu L., Hoxb3 deficiency impairs B lymphopoiesis in mouse bone marrow, Experimental Hematology. 2007, 35(3): 465-75. |
|
Researcher
: Wang C |
|
List of Research Outputs |
|
Chan W.C.W., Ng V.C.W., Wang C., Tsang K.Y., Cheah K.S.E. and Chan D., ER-stress signaling in the pathogenesis of Schmid metaphyseal chondrodysplasia , Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 2007. |
|
Melhado I.G., Cheah K.S.E., Chan D., Tsang K.Y., Chan W.C.W. and Wang C., Towards an understanding of global gene expression changes in hypertrophic chondrocytes undergoing ER stress, Gordon Research Conference in Cartilage Biology. 2007. |
|
Researcher
: Wang J |
|
List of Research Outputs |
|
Huang
J., Watt R.M., Wang J., Leong M.K., Liu D. and Danchin A.L.M., Visualizing becterial
proteomes., 14th International Molecular Medicine Tri-Conference. Feb
27-Mar 2 San Franciso, CA, |
|
Watt R.M., Wang J., Leong M.K., Kung H...F., Cheah K.S.E., Liu D., Danchin A.L.M. and Huang J., Visualizing the proteome of Escherichia coli: an efficient and versatile method for labeling chromosomal coding DNA sequences (CDSs) with fluorescent protein genes., Nucleic Acids Research. 2007, 35(6): 1-11. |
|
Researcher
: Wang X |
|
List of Research Outputs |
|
Wang
X., Lam
V.M.S. and Engel P...C., Functional properties of two mutants of human
glucose 6-phosphate dehydrogenase, R |
|
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. |
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List of Research Outputs |
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Chen B.Y., Lam K.S.L., Wang Y., Wu D., Lam C.W., Shen J., Wong L.C., Hoo R.L.C., Zhang J. and Xu A., Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes., Biochemical and Biophysical Research Communications . 2006, 341: 549-556. |
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Du L., He Y., Wang Y., Zhang H., Ma S., Wong C...K., Wu S...H., Ng F., Huang J., Yuen K...Y., Jiang S., Zhou Y. and Zheng B...J., Recombinant adeno-associated virus expressing the receptor-binding domain of severe acute respiratory syndrome coronavirus S Protein elicits neutralizing antibodies:Implication for developing SARS vaccines., Virology. 2006, 353(1): 6-16. |
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Wang Y., Lam K.S.L. and Xu A., Adiponectin as a negative regulator in obesity-related mammary carcinogenesis. , Cell Research. 2007, 17: 280-2. |
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Wang Y., Xu L., Lam K.S.L., Lu G., Cooper G.J. and Xu A., Proteomic characterization of human serum proteins associated with the fat-derived hormone adiponectin. , Proteomics. 2006, 6: 3862-70. |
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Researcher
: Wang Z |
|
List of Research Outputs |
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Wang Z., Zhou Z., Liu D. and Huang J., Single-Stranded Oligonucleotide-Medicated Gene Repair in Mammalian Cells Has A Mechanism Distinct from Homologous Recombination Repair., 46th Annual Meeting of the American Society for Cell Biology. 2006. |
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Wang Z., Zhou Z., Liu D. and Huang J., Single-Stranded Oligonucleotide-mediated gene repair in mammalian cells has a mechanism distinct from homologous recombination repair. , Biochemical and Biophysical Research Communications. BBRC, 2006, 350 (3): 568-573. |
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Researcher
: Wang Z |
|
List of Research Outputs |
|
Wang Z., Zhou Z., Liu D. and Huang J., Single-Stranded Oligonucleotide-Medicated Gene Repair in Mammalian Cells Has A Mechanism Distinct from Homologous Recombination Repair., 46th Annual Meeting of the American Society for Cell Biology. 2006. |
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Wang Z., Zhou Z., Liu D. and Huang J., Single-Stranded Oligonucleotide-mediated gene repair in mammalian cells has a mechanism distinct from homologous recombination repair. , Biochemical and Biophysical Research Communications. BBRC, 2006, 350 (3): 568-573. |
|
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. |
|
List of Research Outputs |
|
Huang
J., Watt R.M., Wang J., Leong M.K., Liu D. and Danchin A.L.M., Visualizing becterial
proteomes., 14th International Molecular Medicine Tri-Conference. Feb
27-Mar 2 San Franciso, CA, |
|
Researcher
: Wong BCW |
|
List of Research Outputs |
|
Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD: Integrated Cartilage Gene Database for genetic study of cartilage, BMC Genetics . 2007, 8: 4. |
|
Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD:The Integrated Cartilage Gene Database., The Integrated Cartilage Gene Database. 2007. |
|
Researcher
: Wong CKY |
|
List of Research Outputs |
|
Ko K.H., Lam Q.L.K., Zhang M., Wong C.K.Y., Lo K.C., Kahmeyer-Gabbe M., Tsang W.H., Tsang S.L., Chan L.C., Sham M.H. and Lu L., Hoxb3 deficiency impairs B lymphopoiesis in mouse bone marrow, Experimental Hematology. 2007, 35(3): 465-75. |
|
Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Lu L...W., Chan L.C. and Sham M.H., Hoxb3 mutation leads to interleukin-6 dependent plasmacytoma., The 19th Meeting of the European Association for Cancer Research, Budapest, Hungary. July 2006. |
|
Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Chan L.C., Lu L...W. and Sham M.H., The impact of Hoxb3 mutation on plasmacytoma., The 36th Annual Meeting of the Japanese Society for Immunology, Osaka, Japan. December, 2006. |
|
Researcher
: Wong EYM |
|
List of Research Outputs |
|
Wong E.Y.M., Analysis of abnormal craniofacial and ear development of a transgenic mutant with ectopic Hox3expression, PhD Thesis. 2006. |
|
Researcher
: Wong LY |
|
List of Research Outputs |
|
Chan C.S.L., Leung C.M., Wong L.Y., Chan D., Cheah K.S.E. and Tanner J.A., Purification and Identification of Sclerostin Interacting Partners: Steps towards Osteoporosis Therapy with Aptamer-based Inhibitors, 11th Research Postgraduate Symposium, Faculty of Medicine, HKU . 2006. |
|
Shum
K.T., Leung C.M., Wong L.Y., Chan C.S.L. and Tanner J.A., New Approaches for
Therapeutic Aptamer Selection and Delivery, MGH-HKU-Nature |
|
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 identification of sequence elements that mediate stabilization of the CHOP/Gadd153 mRNA by N-(4-hydroxyphenyl)retinamide (4HPR/fenretinide), AACR, April, 2007. |
|
Lee T...C...W., Wong N.S. and Lao T...T., Reduction
of Placental Thioredoxin Expression in Diabetic Pregnancies., American
Society for Cell Biology 46th Annual Meeting, 8-13, Dec., 2006. |
|
Leung K.W., Yung K.K., Mak N.K., Chan Y.S., Fan T.P. and Wong N.S., Neuroprotective effects
of Ginsenoside-Rg |
|
Wong N.S. and Tom W., A characterization of the in vitro effects of metal ions on thioredoxin reductase., XIII Biennial Meeting of the Society for Free radical Research International, Davos, Switzerland, 15th-19th, August, 2006. |
|
Researcher
: Wong PM |
|
List of Research Outputs |
|
Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Lu L...W., Chan L.C. and Sham M.H., Hoxb3 mutation leads to interleukin-6 dependent plasmacytoma., The 19th Meeting of the European Association for Cancer Research, Budapest, Hungary. July 2006. |
|
Wong P.M., Wong C.K.Y., Kong C.T., Tsang S.L., Chan L.C., Lu L...W. and Sham M.H., The impact of Hoxb3 mutation on plasmacytoma., The 36th Annual Meeting of the Japanese Society for Immunology, Osaka, Japan. December, 2006. |
|
Wong
P.M., a Dorothy Hodgkin Postgraduate Award
from the |
|
Wong P.M., Hoxb3mutation leads to interleukin-6 dependent plasmacytoma., MPhil thesis. 2006. |
|
Researcher
: Wynn SL |
|
List of Research Outputs |
|
Cheah K.S.E., Au Y.K., Wynn S.L., Geng G...Y...H. and Cheung K.M.C., Insight into the molecular pathogenesis of campomelic dysplasia revealed by a conditional Sox9 mutant mouse model. , Cold Spring Harbor Meeting on Mouse Molecular Genetics, Cold Spring Harbor, 30 Aug - 3 Sept 2006 New York, USA. 2006. |
|
Researcher
: Xu H |
|
List of Research Outputs |
|
Chin K.T., Xu H., Ching Y.P. and Jin D., Differential subcellular localization and activity of kelch repeat proteins KLHDC1 and KLHDC2, Molecular and Cellular Biochemistry. Springer, 2007, 296: 109-119. |
|
Researcher
: Yang L |
|
List of Research Outputs |
|
Yang
L., Chan
D. and Cheah K.S.E., Genetic
Analyses of Terminal Differentiation of Hypertrophic Chondrocytes., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
|
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 |
|
Chan
D.W., Liu V.W.S., Furukawa T., Tsao G.S.W., Yao K.M., Chan K.K.L. and Ngan H.Y.S., Loss of MKP3 is associated
with cisplatin-resistance and tumorigenicity of ovarian cancer, American
Association for Cancer Research. Annual Meeting 2007. |
|
Cheng
S.A., Tam C.W., Yao K.M. and Shiu S.Y.W., The anti-proliferative
effects of sPDZD2 on prostate and non-prostate cancer cells, FASEB Journal.
9650 ROCKVILLE PIKE, |
|
Madureira P...A., Varshochi R., Constantinidou D., Francis R...E., Coombes R...C., Yao K.M. and Lam E...W., The Forkhead box M1 protein regulates the transcription of the estrogen receptor alpha in breast cancer cells., J Biol. Chem.. 2006, 281(35): 25167-76. |
|
Tam
C.W., Cheng S.A., Ma R.Y.M.,
Yao K.M. and Shiu S.Y.W., Inhibition of prostate
cancer cell growth by human sPDZD2 protein, 3rd PacRim Breast and Prostate
Cancer Meeting, |
|
Tam C.W., Cheng S.A., Ma R.Y.M., Yao K.M. and Shiu S.Y.W., Inhibition of prostate cancer cell growth by human secreted PDZ domain-containing protein 2, a potential autocrine prostate tumor suppressor, Endocrinology. 2006, 147: 5023-5033. |
|
Tam
C.W., Mo H.C.W., Yao K.M. and Shiu S.Y.W., Melatonin inhibits the
proliferation of hormone-refractory prostate cancer cells by up-regulating
p27 Kip1 expression and down-regulating activated androgen signal
transduction via membrane MT1 receptor activation., NCRI Cancer
Conference, |
|
Tam C.W., Mo H.C.W., Yao K.M. and Shiu S.Y.W., Signaling mechanisms of melatonin in antiproliferation of hormone-refractory 22Rv1 human prostate cancer cells: implications for prostate cancer chemoprevention, Journal of Pineal Research. 2007, 42: 191-202. |
|
Tsang
S.W. and Yao K.M.,
Involvement of PDZD |
|
Tsang
S.W., Leung P...S., Cheah K.S.E.,
Thomas M...K. and Yao K.M.,
Involvement of PDZD |
|
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 |
|
Aladin
Kaderbatcha D.M., Lu W.W., Chan D., Yee A.F.Y., Jim J.J.T., Luk K.D.K. and Cheung K.M.C., EXPRESSION OF THE TRP2
ALLELE OF COL |
|
Song Y., Cheung K.M.C., Ho D.W.H., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Yee A.F.Y., Poon S.C.S., 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 to lumbar disc degeneration in Chinese and Japanese., Gordon Research Conference on Cartilage Biology and Pathology, March 4-9, 2007, Ventura, CA, USA. 2007. |
|
Yee
A.F.Y., Cheung
K.M.C. and Chan D., Protein
Expression Profiles of the Intervertebral Disc., 11th Research
Postgraduate Symposium, 7 Dec. 2006. The |
|
Zhou
G., Yee A.F.Y., Chan D., Alini M. and Cheung K.M.C., Hypoxia-related and Stem
Cell-Like Phenotypes of Young, Adult and Aged Intervertebral Disc Cells, International
Society for the Study of the Lumbar Spine. 34th Annual Meeting. |
|
List of Research Outputs |
|
Zhang Y., Yeung M.N., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats, J. Comparative Neurology. 2006, 494: 345-357. |
|
Researcher
: Yeung MY |
|
List of Research Outputs |
|
Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD: Integrated Cartilage Gene Database for genetic study of cartilage, BMC Genetics . 2007, 8: 4. |
|
Yeung M.Y., Smith D.K., Chan S.Y., Wong B.C.W., Cheung K.M.C., Cheah K.S.E., Sham P.C., Chan D. and Song Y., iCartiGD:The Integrated Cartilage Gene Database., The Integrated Cartilage Gene Database. 2007. |
|
Researcher
: Zhang L |
|
List of Research Outputs |
|
Krishnan V., Zhang L. and Zhou Z., Prelamin A Regulates DNA Repair and Senescence via Histone Modifications , 2007 Keystone Symposia Conference - Genome Instability and Repair. 2006. |
|
Researcher
: Zhang Y |
|
List of Research Outputs |
|
Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of heparanase in the normal versus injured spinal cord of adult rats, Soc. Neuroscience Abstract (U.S.A.). 2006, 720: 12. |
|
Zhang
Y., Chau
C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of
heparanase in the normal versus injured spinal cord of adult rats, Society
for Neuroscience ( |
|
Zhang
Y., Chau
C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of
heparanase in the normal versus injured spinal cord of adult rats, Society
for Neuroscience Abstracts ( |
|
Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Expression patterns of heparanase in normal and injured rat spinal cord, Proceedings of the 4th Congress of FAONS. 2006, 67. |
|
Zhang Y., Yeung M.N., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats, J. Comparative Neurology. 2006, 494: 345-357. |
|
Zhang Y., Chan Y.S. and Shum D.K.Y., Molecular cloning characterization and purification of rat pro- and mature heparanase, The 2nd Int'l Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4 Hong Kong. 2007, P11. |
|
Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Proceedings of the 4th Congress of FAONS, Proceedings of the 4th Congress of FAONS. 2006, 67. |
|
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 |
|
Department: |
Biochemistry |
|
Source(s) of Funding: |
Germany/Hong Kong Joint Research Scheme |
|
Start Date: |
01/2007 |
|
Abstract: |
|
1. Understand functions of MT1-MMP in wound healing process 2. Investigate how MT1-MMP affects tumorigenesis, angiogenesis and metastasis |
|
List of Research Outputs |
|
Chan
J.K.M., Chan D. and Zhou Z., Functional Role of MT1-MMP
in FGF Signaling., 11th Research Postgraduate Symposium, 7 Dec. 2006. The |
|
Chau
P.P.Y., Krishnan V., Cheah K.S.E. and Zhou Z., A Comparison of genomic
Instability in Laminopathy-specific Lamin A Mutations., 11th Research
Postgraduate Symposium, 7 Dec. 2006. The |
|
Krishnan V., Zhang L. and Zhou Z., Prelamin A Regulates DNA Repair and Senescence via Histone Modifications , 2007 Keystone Symposia Conference - Genome Instability and Repair. 2006. |
|
Li J.,
Cheah K.S.E. and Zhou Z., Bone Fracture Healing in
Laminopathy-based Premature Aging, 11th Research Postgraduate Symposium, 7
Dec. 2006. The |
|
Wang Z., Zhou Z., Liu D. and Huang J., Single-Stranded Oligonucleotide-Medicated Gene Repair in Mammalian Cells Has A Mechanism Distinct from Homologous Recombination Repair., 46th Annual Meeting of the American Society for Cell Biology. 2006. |
|
Wang Z., Zhou Z., Liu D. and Huang J., Single-Stranded Oligonucleotide-mediated gene repair in mammalian cells has a mechanism distinct from homologous recombination repair. , Biochemical and Biophysical Research Communications. BBRC, 2006, 350 (3): 568-573. |
|
Zhou
Z., An Ideal Mouse Model for Ageing Research.
, HKU-University of |
|
Zhou
Z., Basic Research on ageing (973 project), Ministry
of Science and technology of |
|
Zhou
Z., Laminopathy-based premature ageing – An
Ideal Animal Model for Ageing Research. , Skin Diseases- Human Genetics –
Animal Models, |
|
Zhou Z., Outstanding Research Output 2006, Faculty of medicine, HKU. 2006. |
|
Zhou
Z., Stem Cell therapy of laminopathy-based
premature ageing, Progeria Research Foundation. |
|
Zhou
Z., Stem cells in premature ageing., Stem
Cell Workshop. The |
|
Researcher
: Zhu G |
|
List of Research Outputs |
|
Huang J., Zhu G., Cheah K.S.E. and Chan D., KIF5b is essential for growth plate organization, cytokinesis and chondrocytes differentiation., Gordon Research Conferences: Cartilage Biology & Pathology. March 4-9, Ventura beach Marriott, Ventura, CA, USA. 2007. |
|
Zhu
G., Chan
D., Cheah K.S.E. and Huang J., KIF5b is Essential for Growth
Plate Organization, Cytokinesis and Chondrocytes Differentiation., 11th
Research Postgraduate Symposium, 7 Dec. 2006. The |
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