DEPT OF BIOCHEMISTRY
Researcher
: Cai K |
List of Research Outputs |
Cai
K., Xu R. and Sham M.H., Adeno-associated virus
vector-mediated angiogenic inhibitors suppress lung tumor growth in mice., 10th
Research Postgraduate Symposium, Faculty of Medicine, HKU, |
Researcher
: Chan C |
List of Research Outputs |
Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Mechanistic insight into point mutations in sedlin that result in spondyloepiphyseal dysplasia tarda, FASEB Journal. 2006, 873.9. |
Researcher
: Chan CH |
List of Research Outputs |
Chan C.H., Ip M.S.M. and Shum D.K.Y., Heparan Sulfate/Syndecan-1 Modulates the Balance between Proteinase and Anti-Proteinase in Bronchiectasis, Proteoglycans in Signaling Stockholm (Runo), Sweden, September 7-11,2005. |
Researcher
: Chan CSL |
List of Research Outputs |
Chan C.S.L., Chan D., Cheah K.S.E. and Tanner J.A., Purification and targeting sclerostin: Steps towards, osteoporosis therapy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005. |
Researcher
: Chan D |
Project Title: |
A matrix metalloproteinase detector for in vitro monitoring of enzyme activity |
Investigator(s): |
Chan D, Lam E |
Department: |
Biochemistry |
Source(s) of Funding: |
Research Initiation Programme |
Start Date: |
06/2002 |
Abstract: |
To establish efficient in vitro reporter assays for aggrecanase and other MMPs. |
Project Title: |
The role of matrix remodeling in endochondral bone formation |
Investigator(s): |
Chan D, Cheah KSE |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
10/2002 |
Abstract: |
The project attempts to:- 1) create heterozygous and homzygous mouse mutants expressing MMP-resistant collagen X from the four embryonic stem (ES) cell clones; 2) perform detailed in virto and in vivo analysis to study the molecular and phenotypic consequences on endochondral bone formation. |
Project Title: |
Understanding the molecular basis of skeletal (digit) patterning defects in Brachydactylyl type A-1 |
Investigator(s): |
Chan D, Cheah KSE, He L. |
Department: |
Biochemistry |
Source(s) of Funding: |
NSFC/RGC Joint Research Scheme |
Start Date: |
01/2003 |
Completion Date: |
12/2005 |
Abstract: |
To create a BDA-1 mouse model by gene targeting; to study the impact of the BDA-1 mutation on skeletal morphogenesis; to study the biochemical consequence of BDA-1 mutations using in vitro cell approaches. |
Project Title: |
The biology of digit formation and its pathology in brachydactyly |
Investigator(s): |
Chan D, Mundlos S. |
Department: |
Biochemistry |
Source(s) of Funding: |
Germany/Hong Kong Joint Research Scheme |
Start Date: |
01/2005 |
Abstract: |
To characterize the Ihh-E95K mouse phenotype focusing on endochondral ossification and digit formation; to investigate interacting brachydactyly pathways using a genetic approach in mice; to create Hoxd13 targeting constructs with expanded poly-Als repeats and perform gene-targeting in ES cells. |
Project Title: |
Genomic analysis of the regulation of osteoblast activity in a mouse with generalized hyperostosis |
Investigator(s): |
Chan D |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2005 |
Abstract: |
N/A |
Project Title: |
Genomic analysis of the regulation of osteoblast activity in a mouse with generalized hyperostosis |
Investigator(s): |
Chan D, Cheah KSE, Cheung KMC |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
01/2005 |
Abstract: |
To analyses of specific markers for known regulators of osteoblast differentiation, proliferation and biosynthetic activity; to use gene expression profiling using micro-arrays to gain insights into genes that are expressed in normal and 13del-tg osteoblasts to identify alterations in pathways as a consequence of expressing Col10-13del; to create a transgenic mouse expression of Col10-13del in osteoblasts to assess its expression and correlation to the hyperostosis phenotype. |
List of Research Outputs |
Abbah S.A., Lu W.W., Luk K.D.K., Cheung K.M.C., Liu W., Chan D., Li Z. and Leong J.C.Y., New Bone Formation by Injected With Osteogenic Cells Confined in Sodium Alginate Microcapsules, The XXIII SICOT/SIROT Triennial World Congress held in Istanbul, Turkey, September 2-9, 2005. |
Abbah S.A., Lu W.W., Cheung K.M.C., Zhao F., Chan D., Liu W.G., Li Z., Leong J.C.Y. and Luk K.D.K., Polymer encapsulated human osteoblastic cells form ectopic bone in mice, 52nd Annual Meeting of Orthopaedic Research Society, Chicago, Illinois, March 19-22, 2006. |
Aladin K.D.M., Lu W.W., Cheung K.M.C., Yeung K.W.K. and Chan D., Impact of Trp2 allele mutation of alpha-2 chain in collagen IX on the structural integrity of human annulus fibrosus, European Cells and Materials. 2005, 10(3): 53. |
Aladin
K.D.M., Lu W.W., Cheung K.M.C., Yeung K.W.K. and Chan D., Impact of Trp2 allele
mutation of alpha-2 chain in collagen IX on the structural integrity of human
annulus fibrosus, European Cells and Materials Symposium: Spinal Motion
Segment: From Basic Science to Clinical Application, 4th to 7th July, 2005. |
Aladin
Kaderbatcha D.M., Lu W.W., Cheung K.M.C., Yeung K.W.K. and Chan D., Impact of the Trp2 allele
mutation of the alpha-2 chain in collagen IX on the structural integrity of
human annulus fibrosus., European Cells and Material: ECM VI/SRN I Spinal
Motion Segment: From basic science to clinical application. |
Chan C.S.L., Chan D., Cheah K.S.E. and Tanner J.A., Purification and targeting sclerostin: Steps towards, osteoporosis therapy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005. |
Chan D., Gao B., Hu J.X., Law K.F.S., He L. and Cheah K.S.E., Abnormal Indian Hedgehog Signaling affects Distal Digit Patterning in a Mouse Model with Brachydactyly Type A1, Frontiers in Biomedical Research, The Univeristy of Hong Kong, Hong Kong, Dec 2. 2005. |
Chan
D., ER stress alters the course of
endochondral ossification, Max-Plank Institute for Molecular Genetics, |
Chan
D., Tsang
K.Y., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E. B.,
Yamada Y., Bateman J.F., Cheung K.M.C.
and Cheah K.S.E., Endoplasmic
reticulum stress and reprogramming of hypertrophic chondrocytes, Gordon
Research Conference: Collagen. |
Chan
D., Chan
W.Y., Murphy G. and Cheah K.S.E.,
Mouse model with impaired collagen X degradation at the chondr-osseous
junction, International Workshop on the Skeletal Growth Plate, |
Chan D., Ho G. and Cheung K.M.C., Stem cell therapy for intervertebral disc degeneration, The Croucher Foundation Advanced Study Institute on Stem Cell Research, Nov 14-15. 2005. |
Chan D. and Cheung K.M.C., The effect of severity of degeneration on mesenchymal stem cells' ability to regenerate the intervetebral disc: a rabbit model, Hansjoerg Wyss Foundation Oral Presentation Award European Cells and Materials VI / SRN I Spinal Motion Segment: From Basic Science to Clinical Application, July 4-7 2005. 2005. |
Chan
D., Ho G.,
Leong V.Y.L. and Cheung K.M.C., The effect of severity of
disc degeration on mesenchymal stem cell's ability to regenerate the
intervertebral disc., European Cells and Material: ECM VI/SRN I Spinal
Motion Segment: From basic science to clinical application. |
Chan W.Y., Cheah K.S.E., Ng V.C.W., Murphy G. and Chan D., Mouse model with impaired collagen X degradation at the chondro-osseous junction, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005. |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006. |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25. |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September . 2005. |
Cheung K.M.C., Chen Y., Karppinen J., Chan D., Jim J.J.T., Luk K.D.K., Ala-Kokko L., Leong J.C.Y., Ott J., Sham P.C., Cheah K.S.E. and Song Y., Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in Chinese, Spine. 2006, 31(10): 1143-8. |
Cheung
K.M.C., Jim J.J.T.,
Noponen-Hietala N., Ott J., Karppinen
J., Sahraravand A., Luk K.D.K., Yip S.P.,
Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The Genetics of
intervertebral disc degenertation, European Cells and Material: ECM VI/SRN
I Spinal Motion Segment: From basic science to clinical application. |
Cheung K.M.C., Lu W.W., Luk K.D.K., Wong C.T., Chan D., Shen J.X., Qiu G.X., Zheng Z.M., Li C.H., Liu S.L., Chan W.K. and Leong J.C.Y., Vertebroplasty by use of a strontium containing bioactive bone cement, Spine (Focus Issue). 2005, 30(17S): S84-S91. |
Cheung
K.M.C., Ho G., Chan D. and Leong V.Y.L., regeneration of nucleus
pulposus after disectomy by autologous mesenchymal stem cells: a rabbit
model, European Cells and Material: ECM VI/SRN I Spinal Motion Segment:
From basic science to clinical application. |
Choi M.Y., Chan D., Cheah K.S.E. and Tanner J.A., Functional studies on sedlin, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, 3 Dec . 2005. |
Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Mechanistic insight into point mutations in sedlin that result in spondyloepiphyseal dysplasia tarda, FASEB Journal. 2006, 873.9. |
Guo X., Cheung K.M.C., Chan D. and Irwin M.G., Comparison of the effect of non-selective NSAID and Cycloosygenoase-2 (COX-2) selective NSAID on bone formation - implications for spinal fusion, 40th Annual Meeting of Scoliosis Research Society, Miami, Florida, USA, October 27-30, 2005. |
Guo X., Irwin M.G., Chan D., Tipoe G.L. and Cheung K.M.C., Differential functions of cyclooxygenase 1 and 2 in bone repair, European Cells and Materials. 2005, 10(3): 56. |
Guo X., Irwin M.G., Cheung K.M.C., Chan D. and Tipoe G.L., The Role of Cyclooxygenase 1 and 2 in Bone Repair, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005. |
Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S.P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on familial Early-onset Degenerative Disc Disease(DDD), Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland.. 2006. |
Hui T.Y., Ho G., Cheung K.M.C., Chan D., Cheung W.L. and Chan B.P., Rabbit bone marrow derived mesenchymal stem cells induced collagen gel contraction-fabrication of tissue-like structures with different cell densities, Tissue Engineering. May Ann Liebut, Inc., 2005, 110. |
Jim J.J.T., Noponen-Hietala N., Cheung K.M.C., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration, Spine. 2005, 30: 2735-2742. |
Leung V.Y.L., Ho G., Chan D. and Cheung K.M.C., The effect of severity of degeneration on intervertebral disc regeneration by autologous mesenchymal stem cells, 25th Annual Congress of the Hong Kong Orthopaedic Association, Nov 19-20 2005, Hong Kong. 2005. |
Leung Y.L., Chan D. and Cheung K.M.C., Regeneration of intervertebral disc by mesenchymal stem cells: Potentials, limitations, and future direction, Eur Spine J. 2006, 15 Suppl 15: 406-13. |
Leung Y.L., Ho G., Chan D. and Cheung K.M.C., The effect of severity of degeneration on intervertebral disc regeneration by use of mesenchymal stem cells, 52nd Annual Meeting of Orthopaedic Research Society, Chicago, Illinois, March 19-22, 2006. |
Leung Y.L., Ho G., Cheung K.M.C. and Chan D., The effect of severity of degeneration on intervertebral disc regeneration by use of mesenchymal stem cells, European Cells & Materials Conference, Davos, Switzerland. 2005. |
Li Z., Lu W.W., Ni G., Lam W.M.R., Chan D., Abbah S.A., Yang F., Cheung K.M.C. and Luk K.D.K., Strontium combined with calcium increases vertebral bone mineral density and stiffness in goats, 25th Annual Congress of the Hong Kong Orthopaedic Association, Nov 19-20 2005, Hong Kong. 2005. |
Lo R.L.K., Ng V.C.W., Cheah K.S.E. and Chan D., ER-stress signaling and chondrocyte differentiation in mice, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005. |
Song Y., Ho D.W.H., Cheung K.M.C., Karppinen J., YIP S. P., Leong J.C.Y., Ott J., Luk K.D.K., Cheah K.S.E., Sham P.C. and Chan D., Genetic Linkage analysis of early onset degenerative disc disease in Southern Chinese., HUGO Pacific meeting & Asia-pacific Human Genetics Conference (HUGO-AP 2006), March 6-10, 2006 Academica Sinica, Taipei. 2006. |
Tsang
K.Y., Chan D., Cheslett
D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B.,
Yamada Y., Bateman J.F., Cheung K.M.C.
and Cheah K.S.E., Chondroctes
Alleviate ER Stress Caused by Unfolded Proteins by Reprogramming, The
British Society for Matrix Biology. 25th Anniversary Meeting Pathobiology of
Bone and Cartilage. |
Yee
A.F.Y., Cheung K.M.C. and Chan D., Gene and Protein Expression
Profiles of the Intervertebral Disc: In Health and Disease - A General
Overview, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, |
Yeung K.W.K., Poon R.W., Liu X.Y., Ho J.P., Chung C.Y., Chu P.K., Lu W.W., Chan D. and Cheung K.M.C., Corrosion resistance, mechanical properties and cyto-compatibility of NiTi shape memory alloys using nitrogen, and oxygen plasma immersion ion implantation, Journal of Biomedical Materials Research: Part A. 2005, 75: 256-67. |
Yeung K.W.K., Poon R.W.Y., Liu X.Y., Ho J.P.Y., Chung C.Y., Chu P.Y., Lu W.W., Chan D. and Cheung K.M.C., Enhanced corrosion resistance and biocompatibility by plasma implantation of nickel-titanium alloys: An in-vitro and surface chemical study, 51st Annual Meeting of Orthopaedic Research Society, Washington DC, U.S.A., 2005. |
Yeung K.W.K., Poon R.W.Y., Liu X., Ho J.P.Y., Chung C.Y., Chu P.K., Lu W.W., Chan D. and Cheung K.M.C., Nickel suppression in Ni-Ti alloys by plasma immersion ion implantation surface treatment: new materials for orthopaedic implantation, European Cells and Materials. 2005, 10(3): 78. |
Yeung
K.W.K., Poon R.W.Y., Liu X., Ho J.P.Y., Chung C.Y., Chu P.K., Wu W.W., Chan D. and Cheung K.M.C., Nickle suppression in
Nickle-titanium alloys by plasma immersion ion implanation surface treatmentL
new material for orthopaedic implanation., European Cells and Material:
ECM VI/SRN I Spinal Motion Segment: From basic science to clinical application.
|
Yeung K.W.K., Poon R.W., Liu X.Y., Chung C.Y., Chu P.K., Lu W.W., Chan D. and Cheung K.M.C., Nitrogen Plasma Immersion Ion Implanted Nickel Titanium Alloys For Orthopedic Use, 5th Asian-European International Conference on Plasma Surface Engineering, Qingdao, China, Sept 12-16, 2005.. 2005. |
Yeung
K.W.K., Poon R.W.Y., Liu X.Y., Chung C.Y., Chu P.K., Lu W.W., Chan D. and Cheung K.M.C., Nitrogen plasma immersion
ion implanted nickel titanium alloys for orthopedic use, 5th
Asian-European International Conference on Plasma Surface Engineering, |
Yeung
M.N., Zhou Z., Chan D. and Shum D.K.Y., Expression of heparanase in
newborn mouse growth plates, Glycoconjugate Journal, GlycoXVIII, XVIII
International Symposium on Glycoconjugates, |
Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan Sulfates and Heparanase in the Mineralizing Matrix of Developing Mouse Growth Plate., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Yeung
M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan sulfates and
heparanase at the mineralization front of the developing growth plate., Proteoglycans
in Signaling, |
Researcher
: Chan KMJ |
List of Research Outputs |
Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785. |
Researcher
: Chan KT |
Project Title: |
Investigation of novel RNA-mediated regulation of Hoxb3 gene expression profiles |
Investigator(s): |
Chan KT, Sham MH |
Department: |
Biochemistry |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
11/2005 |
Completion Date: |
11/2006 |
Abstract: |
Hox homeobox genes are transcription factor genes with a clustered genomic organization in both mouse and human. The temporal and spatial specific expressions of Hox genes are essential for their function in regulating a variety of embryonic developmental processes. Recent studies on micro RNA genes in mammalian genomes demonstrated that there are a number of micro RNA genes present within Hox gene clusters. These micro RNA products have specific functions in regulating the expressions of target Hox genes, suggesting that apart from known regulatory mechanisms, RNA-mediated gene expression regulation is important of normal Hox gene function. To investigate RNA mediated control of Hox gene expression, we have performed pilot experiments by both in-silico and experimental approaches. From available databases, we have identified wide-spread conserved anti-sense RNA transcripts in all four Hox gene clusters in the mouse and human genomes, suggesting that these anti-sense RNAs may have important functions in Hox gene regulation. Moreover, we have identified a novel Hoxb3 anti-sense RNA which is expressed in a tissue-specific manner during mouse neural development. Similar anti-sense RNA transcript expression has also been observed for the human HoxA3 gene. Based on these observations, we hypothesize that these anti-sense RNA transcripts may be important for regulating Hox gene expression; and that RNA sequence mediated gene regulation may be a common mechanism for Hox gene regulation. The specific objectives of this project are: (1) To build up a complete expression profile of the differential mRNA transcripts for Hox genes; (2) To characterize both the structure and the expression patterns of the Hoxb3 anti-sense RNA transcript at different stages of mouse embryogeneis; (3) To perform a cell based functional analysis to examine the effect of anti-sense RNA on the expression of the normal Hoxb3 sense mRNA transcript. |
List of Research Outputs |
Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005. |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Researcher
: Chan LC |
List of Research Outputs |
Ng M.H., Jin D. and Chan L.C., Ras Signalling in Mll-Mediated Leukaemia, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Researcher
: Chan SF |
List of Research Outputs |
Ching
Y.P., Chan S.F. and Jin D., A centrosomal target of human
T-cell leukemia virus type I oncoprotein Tax on the road to genome
instability, The Croucher Advanced Study Institute “Signaling in Cell
Growth abd Differentiation”. The |
Ng D.C.H., Chan S.F., Kok K.H., Yam J.W.P., Ching Y.P., Ng I.O.L. and Jin D., Mitochondrial targeting of growth suppressor protein DLC2 through the START domain, FEBS Letters . 2006, 580(1): 191-8. |
Researcher
: Chan SY |
List of Research Outputs |
Tang L.F., Chan S.Y., Sham P.C. and Song Y., In silico mapping of quantitative trait loci affecting bone mineral density in mice., HUGO Pacific meeting & Asia-Pacific Human Genetics Conference (HUGO-AP 2006) March 6-10,2006 Academica Sinica, Taipei. 2006. |
Researcher
: Chan WCW |
List of Research Outputs |
Chan
D., Tsang K.Y., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B.,
Yamada Y., Bateman J.F., Cheung K.M.C.
and Cheah K.S.E., Endoplasmic
reticulum stress and reprogramming of hypertrophic chondrocytes, Gordon
Research Conference: Collagen. |
Tsang
K.Y., Chan D., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B.,
Yamada Y., Bateman J.F., Cheung K.M.C.
and Cheah K.S.E., Chondroctes
Alleviate ER Stress Caused by Unfolded Proteins by Reprogramming, The
British Society for Matrix Biology. 25th Anniversary Meeting Pathobiology of
Bone and Cartilage. |
List of Research Outputs |
Chan
D., Chan W.Y., Murphy G.
and Cheah K.S.E., Mouse model with
impaired collagen X degradation at the chondr-osseous junction, International
Workshop on the Skeletal Growth Plate, |
Chan W.Y., Cheah K.S.E., Ng V.C.W., Murphy G. and Chan D., Mouse model with impaired collagen X degradation at the chondro-osseous junction, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005. |
Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia . 2005. |
Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Hoxb3 is involved in the endothelin-1 signaling pathway in patterning the facial branchial arches, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005. |
Researcher
: Chau CH |
List of Research Outputs |
Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42. |
Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57. |
Researcher
: Chau PYP |
List of Research Outputs |
Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785. |
Researcher
: Cheah KSE |
Project Title: |
The role of Type II procollagens encoded by alternatively spliced forms of aI(II) procollagen mRNA in cartilage differnetiation and growth |
Investigator(s): |
Cheah KSE |
Department: |
Biochemistry |
Source(s) of Funding: |
Arthritis and Rheumatism Council (ARC) - General Award |
Start Date: |
12/1993 |
Abstract: |
To gain insight into the function of type IIA procollagen by: a) performing a loss-of function test by introducing into the mouse germ line, a mutation in the [alpha]1(II) collagen gene in which exon 2 is deleted, using gene targeting; determining the phenoypic consequence of reduced levels of expression or failure to express type IIA procollage; generating monoclonal antibodies to the cysteine-rich domain within the aminopropeptide of type IIA procollagen. |
Project Title: |
Defining the role of the transcription factor Sox9 in skeletal development by tissue-specific gene inactivation |
Investigator(s): |
Cheah KSE, Lovell-Badge R.H. |
Department: |
Biochemistry |
Source(s) of Funding: |
UK/Hong Kong Joint Research Scheme |
Start Date: |
02/1998 |
Abstract: |
To inactivate the mouse Sox9 gene selectively and specifically in developing cartilage tissue in order to understand the role of Sox9 in skeletal formation and the relationship between loss of Sox9 gene function and skeletal malformation. |
Project Title: |
Molecular and transgenic approaches for the identification of genes regulated by SOX9 during mouse development |
Investigator(s): |
Cheah KSE |
Department: |
Biochemistry |
Source(s) of Funding: |
Outstanding RGC Projects |
Start Date: |
09/1998 |
Abstract: |
To use a combination of molecular cloning, cell culture and transgenic/chimeric mouse approaches to: 1) identify other downstream targets of SOX9; 2) test the possibility that SOX9 may have a role as a negative regulator of transcription; 3) study SOX9 function by determining the developmental consequences of mis-expression of the gene in transgenic mice. These studies will provide fundatmental information on the mechanisms by which SOX9 regulates gene expression, with profound implications for understanding it's development role and the molecular basis of CD caused by loss of SOX9 function. |
Project Title: |
In vivo functional analysis of the SOX9 transcription factor in regulating developmental gene expression |
Investigator(s): |
Cheah KSE, Chan D, Tam P.P.L. |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
09/2001 |
Completion Date: |
08/2005 |
Abstract: |
To use transactivation of the COL2A1 enhancer reporter upon ectopic expression of SOX in transgenic mice to assess: i) the functional requirement for SOX9 to activate its target genes by testing the competence of SOX2 and SOX8 to substitute for SOX9; ii) the requirements for the N-, HMG, C terminus regions of SOX9 in activating its target genes by testing the competence of SOX9-SOX2 and SOX9-SOX8 chimeric proteins to substitute for SOX9 by gene targeting into the Sox9 locus in mouse ES cells, to test further the competence of the alternative SOX gene and/or relevant chimeric SOX protein to mediate the differentiation and developmental roles of SOX9, with particular focus on chondrogenesis. |
Project Title: |
Genomic approaches to uncover functionally relevant signalling pathways in craniofacial development |
Investigator(s): |
Cheah KSE, Wong BCW, Sham MH, Chung SK,
Huang J, Smith DK, Wicking |
Department: |
Biochemistry |
Source(s) of Funding: |
Central Allocation Vote - Group Research Project |
Start Date: |
06/2002 |
Abstract: |
To build a multidisciplinary, competitive and productive research team of a critical size with the central theme of uncovering genetic relationships and functionally relevant signalling pathways in craniofacial development in order to make an impact in this important research area, currently at the fore-front of genomic biology; to pool expertise and resources, employing complementary genetic approaches in mice, coupled with advanced technology to reveal networks of genes and the complex interactions that specify morphology of the head skeleton and facial structures; to use and develop bioinformatics tools to analyse the expression data and formulate hypotheses on genetic relationships and the pathways regulating patterning, formation and growth of the craniofacial primordia; to test the hypotheses on potential functional relationships and molecular interactions revealed by the bioinformatic analyses, in the worm model and in the yeast two hybrid system. |
Project Title: |
The regulation and role of Sox2 in the circling, deaf and yellow mouse mutants Yellow submarine (Ysb) and Light coat and circling (Lcc) |
Investigator(s): |
Cheah KSE |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
10/2002 |
Completion Date: |
09/2006 |
Abstract: |
The current project will test some hypotheses of Sox2 function using gene mapping, comparative genomics, genetics and transgenesis to: - i) identify the chromosomal breakpoints in Lcc; ii) identify the mutations in Ysb and Lcc and determine whether these have disrupted cis-elements which regulate Sox2 expression in the inner ear and hair follicle; iii) validate these findings by functional rescue/mutagenesis/genetic experiments in transgenic mice; iv) identify the molecular developmental changes in inner ear hair cell and hair follicle morphogenesis. |
Project Title: |
Understanding gene function and molecular bases of disease using transgenic and gene targeting technology |
Investigator(s): |
Cheah KSE, Chan SY, Chan LC, Sham MH, Chung SK, Chow BKC, Kung H, Chan D, Huang J, Lin MC, Zhang JCL, Waye MMY, Lung M.L., Chow KL, Tam P.P.L., Chan W.Y., Lui VCH, Yao KM |
Department: |
Biochemistry |
Source(s) of Funding: |
Central Allocation Vote - Group Research Project |
Start Date: |
06/2003 |
Completion Date: |
05/2006 |
Abstract: |
To continue to build up a multidisciplinary, competitive and productive research team of a critical size pooling expertise and resources to tackle several fore-front issues of human diseases using animal models; to maintain a highly productive Transgenic Core Facility (TCF) with extended "clientele", facilitating the timely generation of genetically modified mice for more projects which will serve to provide new knowledge in understanding gene function and as models of human disease, provide insight into the molecular pathogenesis of disease. |
Project Title: |
Genetic manipulation and analyses of the regulation of chondrocyte hypertrophy |
Investigator(s): |
Cheah KSE, Chan D |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
09/2003 |
Abstract: |
To understand the roles of Ihh and Ppr specifically in hypertrophic chondrocytes (HCs) and will dissect the mode of action of the Ihh and PPR pathways in HCs, in vivo, in transgenic and conditional knockout mice, Specially we will: 1) Investigate whether abnormal Ihh signaling and /or processing in 13del HCs is a primary cause of the differentiation abnormality by a) ablating Smoothened (Smo), the transducer of Ihh signaling in 13 del and wild-type HCs and b) over-expressing either Ihh or a non-secreted and unprocessed form of Ihh in normal HCs. 2) By the same rationale, study the role of the PTHrP/PPR pathway by ablating PPR in 13 del and wild-type HCs. |
Project Title: |
Functional analysis of SM22[beta] by tissue-specific targeted deletion in mice |
Investigator(s): |
Cheah KSE, Lau CP, Feil R., Parmacek M.S., Zhang JCL |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
09/2003 |
Abstract: |
To determine the general role of SM22[beta] in a cell; to understand the specific role of SM22[beta] in cardiovascular development. |
Project Title: |
Genetic manipulation and analyses of the regulation of chondrocyte hypertrophy |
Investigator(s): |
Cheah KSE, Chan D |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
09/2003 |
Abstract: |
N/A |
Project Title: |
Strategic research theme of development and reproduction under the strategic research area of health development framework and seed funding proposal |
Investigator(s): |
Cheah KSE, Ho PC, Wong WT, Sham PC, Chin FYL, Chan BP |
Department: |
Biochemistry |
Source(s) of Funding: |
Seed Funding for Strategic Research Theme |
Start Date: |
05/2005 |
Abstract: |
To promote and facilitate partnership that are highly interactive, collaborative and multidisciplinary; to achieve research excellence in the fields of development and reproduction and, through their translation, better treatment and prevention of diseases; to raise community awares and understanding of important issues and advances concerning healthy development and reproduction and treatment of diseases. |
Project Title: |
Functional and genetic analyses of the role of type IIA procollagen in morphogenesis and as a regulator of BMP and TGFβ signaling |
Investigator(s): |
Cheah KSE |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
08/2005 |
Abstract: |
N/A |
Project Title: |
Functional and genetic analyses of the role of type IIA procollagen in morphogenesis and as a regulator of BMP and TGFβ signaling |
Investigator(s): |
Cheah KSE, Chan D |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
08/2005 |
Abstract: |
To address the hypothess that IIA regulates nodal signaling by a) maintaining the midline barrier or b) by interacting with Nodal protein. |
Project Title: |
Genomic approaches to uncover functionally relevant signalling pathways in craniofacial development |
Investigator(s): |
Cheah KSE, Chan WY, Chow KL, Huang J, Sham MH, Smith DK, Bronner-Fraser M, Fraser SE, Tam PPL, Wu DKW, Chung SK, Zhou Z |
Department: |
Biochemistry |
Source(s) of Funding: |
Central Allocation Vote - Group Research Project |
Start Date: |
03/2006 |
Abstract: |
To uncover and understand the roles of two sets of transcription factor genes: Hos genes in establishing the complex pattern and structures of the inner ear and middle ear; and Sox9 and Sox10 in the early induction of the inner ear and the later specification of cell fate or type; to generate hypotheses on genetic relationships, molecular interactions and pathways involving Hoxa/b, Six1, Sox9 and Sox10 using simpler model systems such as the worm; to validate the hypotheses on molecular interactions by molecular, biochemical and cellular approaches. |
List of Research Outputs |
Au T.Y.K., Wynn S.L., Cheah K.S.E. and Cheung K.M.C., The use of a mouse model to understand the role of SOX9 in campomelic dysplasia and the notochord, 25th Annual Congress of the Hong Kong Orthopaedic Association, Nov 19-20 2005, Hong Kong. 2005. |
Au Y.K., Wynn S.L., Cheung K.M.C. and Cheah K.S.E., Foxa2 minimal notochord enhancer element mediates Cre expression in the node and notochord, Mechanisms of Development. 2005, 122 (Supp 1): S88. |
Au Y.K., Wynn S.L., Cheung K.M.C. and Cheah K.S.E., Foxa2 minimal notochord enhancer element mediates Cre expression in the node and notochord, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia. 2005. |
Au
Y.K., Cheung K.M.C. and Cheah K.S.E., In vivo functional
analysis of SOX9 by conditional expression of a mutant SOX9, SOx9Y440X, 10th
Research Postgraduate Symposium, Faculty of Medicine, HKU. |
Chan C.C.Y., Luk K.D.K. and Cheah K.S.E., Understanding the function of the SEDL gene and the molecular pathogenesis of spondyloepiphyseal dysplasia tarda, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005. |
Chan C.S.L., Chan D., Cheah K.S.E. and Tanner J.A., Purification and targeting sclerostin: Steps towards, osteoporosis therapy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005. |
Chan D., Gao B., Hu J.X., Law K.F.S., He L. and Cheah K.S.E., Abnormal Indian Hedgehog Signaling affects Distal Digit Patterning in a Mouse Model with Brachydactyly Type A1, Frontiers in Biomedical Research, The Univeristy of Hong Kong, Hong Kong, Dec 2. 2005. |
Chan
D., Tsang K.Y., Cheslett D., Chan W.C.W., So C.L., Kwan K. M., Hunziker E.B., Yamada
Y., Bateman J.F., Cheung K.M.C. and Cheah K.S.E., Endoplasmic reticulum
stress and reprogramming of hypertrophic chondrocytes, Gordon Research
Conference: Collagen. |
Chan
D., Chan W.Y., Murphy G. and Cheah K.S.E., Mouse model with
impaired collagen X degradation at the chondr-osseous junction, International
Workshop on the Skeletal Growth Plate, |
Chan W.Y., Cheah K.S.E., Ng V.C.W., Murphy G. and Chan D., Mouse model with impaired collagen X degradation at the chondro-osseous junction, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005. |
Cheah
K.S.E., ER stress in the hypertrophic
chondrocyte. , Workshop on the Skeletal Growth Plate, 11-15 June 2006, |
Cheah
K.S.E. and Zhang
J.C.L., Procollagen IIA deficient mice. , |
Cheah
K.S.E., Chair a session and invited
speaker, in Gordon Research Conference on Collagen, 24-29 July, 2005 in |
Cheah
K.S.E., Chair a session and invited
sympoisum speaker in 6th Pan Pacific Connective Tissue Societies Symposium,
30 November - |
Cheah K.S.E., Discovering the crucial link for sensory development in the inner ear, Invited scientific talk at Institute of Biomedical Science, Hong Kong Branch, 19 May 2006 Hong Kong . 2006. |
Cheah
K.S.E., Discussion leader and speaker in
Gordon Research Conference on Collagen, 24-29 July 2005, |
Cheah K.S.E., Genetic basis of skeletal dysplasia, ear development & congenital deafness – lessons from mose models of human malformations, Invited seminar at Hong Kong College of Paediatricians, 27 November 2005 Hong Kong. 2005. |
Cheah
K.S.E., Member, Scientific Programme
Committee , HGM2006 (Human Genome meeting) , |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006. |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25. |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September . 2005. |
Cheah K.S.E., Sox2 as a master regulator of prosensory development in the mouse inner ear, Invited seminar at Department of Biochemistry, the Chinese University of Hong Kong, 24 June 2006 Hong Kong. 2006. |
Cheah
K.S.E., Sox2, Sox18 and hair follicle
development. , Sox Meeting, 30 August – |
Cheah K.S.E., The role of Sox genes in inner ear development, Invited seminar at the Institute of Molecular and Cell Biology, National University of Singapore, 8 March 2006 Singapore. 2006. |
Cheah K.S.E., The role of procollagen IIA as a facilitator of BMP signaling in Heart development, Croucher Advanced Study Institute [ASI] on Signaling in Cell Growth and Differentiation, HKUST 16-20 January 2006 Hong Kong. 2006. |
Cheah
K.S.E., The role of procollagen IIA as a
facilitator of BMP signaling, 6th Pan Pacific Connective Tissue Societies
symposium 30 November - 3 December, |
Cheah
K.S.E., Unraveling pathways and disease
mechanisms using mouse models, Transcriptome 2005 International
Conferences, |
Cheung K.M.C., Chen Y., Karppinen J., Chan D., Jim J.J.T., Luk K.D.K., Ala-Kokko L., Leong J.C.Y., Ott J., Sham P.C., Cheah K.S.E. and Song Y., Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in Chinese, Spine. 2006, 31(10): 1143-8. |
Cheung
K.M.C., Jim J.J.T.,
Noponen-Hietala N., Ott J., Karppinen
J., Sahraravand A., Luk K.D.K., Yip S.P.,
Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The Genetics of intervertebral
disc degenertation, European Cells and Material: ECM VI/SRN I Spinal
Motion Segment: From basic science to clinical application. |
Choi M.Y., Chan D., Cheah K.S.E. and Tanner J.A., Functional studies on sedlin, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, 3 Dec . 2005. |
Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Mechanistic insight into point mutations in sedlin that result in spondyloepiphyseal dysplasia tarda, FASEB Journal. 2006, 873.9. |
Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S.P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on familial Early-onset Degenerative Disc Disease(DDD), Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland.. 2006. |
Jim J.J.T., Noponen-Hietala N., Cheung K.M.C., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration, Spine. 2005, 30: 2735-2742. |
Kong C.T., Sham M.H., So C.W.E., Cheah K.S.E., Chen S.J. and Chan L.C., The Mll-Een knockin fusion gene enhances proliferation of myeloid progenitors derived from mouse embryonic stem cells and causes myeloid leukaemia in chimeric mice, Leukemia. 2006, 20: 1829–1839. |
Li J. and Cheah K.S.E., The role of Indian Hedgehog in chondrocyte hypertrophy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005. |
Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785. |
Lo R.L.K., Ng V.C.W., Cheah K.S.E. and Chan D., ER-stress signaling and chondrocyte differentiation in mice, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005. |
Song Y., Ho D.W.H., Cheung K.M.C., Karppinen J., YIP S.P., Leong J.C.Y., Ott J., Luk K.D.K., Cheah K.S.E., Sham P.C. and Chan D., Genetic Linkage analysis of early onset degenerative disc disease in Southern Chinese., HUGO Pacific meeting & Asia-pacific Human Genetics Conference (HUGO-AP 2006), March 6-10, 2006 Academica Sinica, Taipei. 2006. |
Tsang
K.Y., Chan D., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B.,
Yamada Y., Bateman J.F., Cheung K.M.C.
and Cheah K.S.E., Chondroctes
Alleviate ER Stress Caused by Unfolded Proteins by Reprogramming, The
British Society for Matrix Biology. 25th Anniversary Meeting Pathobiology of
Bone and Cartilage. |
Wong E.Y.M., Chan Y.S., Wu D.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in mouse hindbrain causes abnormal ear development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September . 2005. |
Wong E.Y.M., Chan Y.S., Wu D.K. and Cheah K.S.E., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development., Mechanisms of Development . 2005, 122 (Supp 1): S88. |
Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia . 2005. |
Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Hoxb3 is involved in the endothelin-1 signaling pathway in patterning the facial branchial arches, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005. |
Researcher
: Chen Y |
List of Research Outputs |
Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Hui K.C., Ng P.K.M., Mak W.W., Jin D. and Song Y., Association of the cholesterol 24S-hydroxylase polymorphism with Alzheimer's disease in Chinese, HUGO 2006 Helsinki, Finland, 31 May-03 June 2006 . 2006. |
Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Ng K.M., Mak W., Jin D., st. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese. , Dement Geriatr Cogn Disord. 2006, 22: 399-404. |
Researcher
: Cheng LYL |
Project Title: |
A concordance study of the importance of autosomal short tandem repeat (STR) and Y-chromosome STR in the Chinese community |
Investigator(s): |
Cheng LYL, Tan-Un KC |
Department: |
Biochemistry |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
11/2002 |
Abstract: |
In recent years, Short Tandem repeat
(STR) and microsatellite analyses offer invaluable evidences in forensic
science casework in court. Despite the well established database in the |
List of Research Outputs |
Lai K.K.S., Lo I.F.M., Tong T.M.F., Cheng L.Y.L. and Lam S.T.S., Detecting exon deletions and duplications of the DMD gene using Multiplex Ligation-dependent Probe Amplification (MLPA)., Clinical Biochemistry. 2005. |
Researcher
: Cheung MS |
List of Research Outputs |
Tong
H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the
Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific
Community - Stem Cells, Senescence and Cancer. |
Tong
H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the
RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of
Medicine, HKU, |
Researcher
: Chin KT |
List of Research Outputs |
Chin
K.T., Wong
C.M., Ng I.O.L. and Jin D., Functional characterization of
liver-enriched transcription factor CREB-H (poster 1989). , The American
Society for Cell Biology 45th Annual Meeting, |
Chin
K.T., Siu
Y.T., Siu K.L. and Jin D., Tax-induced recruitment of TORC
family coactivators is required for transcriptional activation of the human
T-cell leukemia virus type 1 long terminal repeats (invited discussant). , The
Leukemia and Lymphoma Society's 2005 Stohlman Scholars Symposium, Renaissance
|
Researcher
: Ching YP |
Project Title: |
The functional characterisation of Pak5 and caspase 4 interaction- a role in apoptosis |
Investigator(s): |
Ching YP |
Department: |
Pathology |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
02/2004 |
Completion Date: |
01/2006 |
Abstract: |
To confirm the interaction of Pak5 and caspase 4 using three independent assays, including co-immunoprecipitation, co-immunostaining and GST affinity pull down assays; to map the minimal binding region of these two proteins and develop functional assays to assess the functional outcome of this interaction; to determine if Pak5 plays a role in apoptosis by regulating the caspase 4. |
Project Title: |
Roles and regulation of group II p21-activated protein kinases:-implications in cancer metastasis |
Investigator(s): |
Ching YP |
Department: |
Pathology |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2005 |
Abstract: |
N/A |
Project Title: |
Roles and regulation of group II p21-activated protein kinases:-implications in cancer metastasis |
Investigator(s): |
Ching YP, Jin D, Ng IOL |
Department: |
Pathology |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
01/2005 |
Abstract: |
To study: (1) Characterisation of the interaction between Pak5 and NM23 i) co-immunoprecipitation of Pak5 adn NM23 ii) defining the binding domain between Pak 5 and NM23 iii) xploring the interaction between Pak4 adn NM23. (2) Impact of Pak5-NM23 interaction in the biochemical properties of Pak5 and NM23 i) nucleotide diphosphate kinase activity ii) GTPase activating activity iii) in vitro kinase activity iv) subcellular localisation. 3) Roles of PakII in cancer metastasis using HCC as a model i) expression profile of Pak4 in HCC ii) clinicopathological analysis iii) cell invasion assay. |
Project Title: |
Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer |
Investigator(s): |
Ching YP |
Department: |
Pathology |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
07/2005 |
Abstract: |
To characterize the overexpression of Pak1 protein and its activities in human HCC; to delineate the signaling pathways mediated by Pak1 in HCC; to investigate the roles of Pak1 in the metastasis of HCC. |
Project Title: |
Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer |
Investigator(s): |
Ching YP |
Department: |
Pathology |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2006 |
Abstract: |
N/A |
Project Title: |
Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer |
Investigator(s): |
Ching YP, Ng IOL, Jin D, Yau TO |
Department: |
Pathology |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
01/2006 |
Abstract: |
(1) To characterize the mechanisms leading to Pak1 overexpression in human HCC; (2) to delineate the roles of Pak1 in hepatocarcinogenesis: (i) Phosphorylation of possible downstream targets of Pak1 in human HCCs. (ii) characterization of the tumorigenic activity of Pak1 in HCC cells. (iii) characterization of the anti-apoptotic activity of Pak1 in HCC cells. (3) to investigate the role of Pak1 in cancer metastasis: >(i) regulation of cell motility and cell adhesion by Pak1 in HCC cells. (ii) HGF/Rac1/Cdc42/Pak1 signaling in HCC metastasis. (iii) HGF/Pak1 mediated angiogenic activity. (iii) HGF/Pak1 mediated angiogenic activity.</I |
Project Title: |
Functional characterization of a putative tumour suppressor, AMP-activated protein kinase, in liver cancer |
Investigator(s): |
Ching YP |
Department: |
Pathology |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
02/2006 |
Abstract: |
Purpose of study Liver cancer
(hepatocellular carcinoma, HCC) is one of the most common cancers in the world,
especially in |
List of Research Outputs |
Researcher
: Choi MY |
List of Research Outputs |
Choi M.Y., Chan D., Cheah K.S.E. and Tanner J.A., Functional studies on sedlin, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, 3 Dec . 2005. |
Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Mechanistic insight into point mutations in sedlin that result in spondyloepiphyseal dysplasia tarda, FASEB Journal. 2006, 873.9. |
Researcher
: Choy EYW |
List of Research Outputs |
Choy E.Y.W., Kok K.H. and Jin D., Construction of New DNA Vectors Based on Promoters of Epstein-Barr Virus-Encoded Small RNAS For Expression of Small Hairpin RNAS in Mammalian Cells., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Choy E.Y.W., Kok K.H. and Jin D., Construction of new DNA vectors based on promoters of Epstein-Barr virus-encoded small RNAs for expression of small hairpin RNAs in mammalian cells., Cold Spring Harbor Laboratory 2005 Meeting on RNAi, Cold Spring Harbor, New York, USA, September 28 to October 2, 2005. . 2005. |
Researcher
: Chun CS |
List of Research Outputs |
Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367. |
Researcher
: Dung WF |
List of Research Outputs |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006. |
Researcher
: Garcia-Barcelo MM |
Project Title: |
Role of RET regulatory polymorphisms in Hirschsprung's disease |
Investigator(s): |
Garcia-Barcelo MM, Tam PKH, Ganster RW |
Department: |
Surgery |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
02/2004 |
Completion Date: |
01/2006 |
Abstract: |
To identify and functionally test a RET susceptibility locus which may predispose to disease more than 60% of the Chinese HSCR patients and to replicate our findings in an extended sample. |
Project Title: |
RET regulatory polymorphisms and susceptibility to Hirschsprung's disease |
Investigator(s): |
Garcia-Barcelo MM, Tam PKH, Ganster RW, Sham P.C. |
Department: |
Surgery |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
09/2004 |
Abstract: |
To study the effect of the RET promoter SNPs on transcription, independently and in conjection with other 5' cis-regulatory elements; to identify the transcription factor functioning at the SNPs site; to investigate whether there is functional and/or physical interactions between PHOX2B and the RET promoter; to test our genetic observations on a larger sample of Chinese HSCR patients; to investigate whether there is association between the transmission of HSCR-susceptibility RET haplotypes and PHOX2B-associated polymorphisms in affected individuals. |
Project Title: |
Study of the molecular basis of anorectal malformations |
Investigator(s): |
Garcia-Barcelo MM, Tam PKH, Lui VCH |
Department: |
Surgery |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
01/2005 |
Completion Date: |
12/2005 |
Abstract: |
The main objective of this project is: To evaluate the human SHH, GLI3, HOXD12, HOXD13, SALL1, HLXB9, EPHB2 genes as disease susceptibility loci for anorectal malformations. Data provided by mutant mice studies (mutant mice for these genes present with a phenotype resembling ARM) suggest that these genes are likely to be implicated in the pathology of ARM. |
Project Title: |
RET regulatory polymorphisms and susceptibility to Hirschsprung's disease |
Investigator(s): |
Garcia-Barcelo MM |
Department: |
Surgery |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2005 |
Abstract: |
N/A |
Project Title: |
Study of the molecular basis of anorectal malformations |
Investigator(s): |
Garcia-Barcelo MM |
Department: |
Surgery |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2006 |
Abstract: |
N/A |
Project Title: |
Study of the molecular basis of anorectal malformations |
Investigator(s): |
Garcia-Barcelo MM, Lui VCH, Yuan Z.W., Tam PKH |
Department: |
Surgery |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
01/2006 |
Abstract: |
To evaluate in patients with isolated ARM and/or VACTERL those genes known to be implicated in ARM according to data provided by i)mutant mice studies and, ii) their role in syndromes that include ARM as part of their spectrum (SHH, GLI3, HOXD12, HOXD13, SALL1, HLXB9, EPHB2); to investigate the gene expression profile during the development of the anorectal region in both, normal and teratogen (ethylenethiourea, ETU)-induced ARMs rat fetuses; to evaluate the genes differentially expressed in the control and in the teratogen ARM-induced embryos as candidates for ARM in humans. |
List of Research Outputs |
Researcher
: Ho DWH |
List of Research Outputs |
Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S.P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on familial Early-onset Degenerative Disc Disease(DDD), Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland.. 2006. |
Ho
D.W.H., Polymorphism of Asporin Increases
Susceptibility and Severity to Degenerative Disc Disease., 10th Research
Postgraduate Symposium, Faculty of Medicine, HKU, |
Song Y., Ho D.W.H., Cheung K.M.C., Karppinen J., YIP S.P., Leong J.C.Y., Ott J., Luk K.D.K., Cheah K.S.E., Sham P.C. and Chan D., Genetic Linkage analysis of early onset degenerative disc disease in Southern Chinese., HUGO Pacific meeting & Asia-pacific Human Genetics Conference (HUGO-AP 2006), March 6-10, 2006 Academica Sinica, Taipei. 2006. |
Researcher
: Huang J |
Project Title: |
Identification of myosin VA interacting proteins |
Investigator(s): |
Huang J, |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
09/2001 |
Completion Date: |
08/2005 |
Abstract: |
To use biochemical, molecular biology and cell biology techniques to evaluate the candidates that are likely to be the proteins mediating MyoVA binding to the cargoes; to identify more MCP candidates as well as other proteins that are important for MyoVA function. |
Project Title: |
RNA-DNA hybrid oligonucleotide mediated site-specific repair and gene therapy |
Investigator(s): |
Huang J, Liu DP |
Department: |
Biochemistry |
Source(s) of Funding: |
Matching Fund for Hi-Tech Research and
Development Program of |
Start Date: |
01/2003 |
Abstract: |
To establish the reporter system for RDO and SSO mediated mutagenesis in mouse ES cells; to investigate the methods to improve the mutagenesis efficiency of RDO- and SSO-mediated mutagenesis; to study the mechanisms underlying SSO-mediated mutagenesis. |
Project Title: |
DNA recombineering mediated by single stranded oligonucleotides |
Investigator(s): |
Huang J, Cheah KSE, Watt RM, Liu DP |
Department: |
Biochemistry |
Source(s) of Funding: |
NSFC/RGC Joint Research Scheme |
Start Date: |
03/2003 |
Completion Date: |
02/2006 |
Abstract: |
To understand detailed biophysical characterization o the [beta] protein; to identify endogenous proteins essential for Red-mediated recombination in E. coli; to introduce [beta] into mammalian cell lines; to study the mechanism of SSO-mediated mutagenesis in mammalian cells. |
Project Title: |
Helicases as antiviral drug targets |
Investigator(s): |
Huang J, Zheng B, Sun H |
Department: |
Biochemistry |
Source(s) of Funding: |
Research Fund for the Control of Infectious Diseases - Full Grants |
Start Date: |
06/2004 |
Completion Date: |
05/2006 |
Abstract: |
To provide a foundation for antiviral drug development, we will expand our screen to identify more helicase inhibitors against SCV. We will also validate SCV helicase as drug target. |
Project Title: |
Development of a novel system for recombinant protein production |
Investigator(s): |
Huang J, Danchin A.L.M. |
Department: |
Biochemistry |
Source(s) of Funding: |
Seed Funding Programme for Applied Research |
Start Date: |
10/2004 |
Completion Date: |
10/2005 |
Abstract: |
To study in silicon identification of genetic elements necessary for high level protein production; to develop an efficient and versatile recombinant expression system for the expression of recombinant proteins; to carry out genetic modification of P. haloplanktis TAC125 for the improvement of protein production. |
Project Title: |
Development of an Efficient Recombinant Protein Expression System in Pseudoalteromonas haloplanktis TAC125 |
Investigator(s): |
Huang J, Danchin A.L.M. |
Department: |
Biochemistry |
Source(s) of Funding: |
France/Hong Kong Joint Research Scheme - Travel Grants |
Start Date: |
01/2005 |
Abstract: |
In silico identification of cold-adapted promoters, strongly and tightly regulated by simple environmental changes, genetic modifications necessary to improve protein production; development of an efficient and versatile recombinant expression system for the expression of recombinant proteins; genetic modification of Pesudoalteromonas haloplanktis TAC125 for the improvement of protein production. |
Project Title: |
Functions of the ubiquitously expressed kinesin in Purkinje neurons |
Investigator(s): |
Huang J, Yip HKF, Wu W, Mugnaini E., Copeland N.G., Jenkins NA |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
01/2005 |
Abstract: |
To determine the KhcU mutation effect on overall cerebellum development; to determine whether PC can project their processes to the target area; determine the localization of ER, Golgi complex, mitochondria, synaptic vesicles and lysosomes; to determine whether KhcU-mediated transport is required for normal MyoVA distribution and neurite out growth; to determine the ultrastructures of KhcU-deficiency PC. |
Project Title: |
Functions of the ubiquitously expressed kinesin in Purkinje neurons |
Investigator(s): |
Huang J |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2005 |
Abstract: |
N/A |
Project Title: |
Determine the functions of the putative metal-binding domain of SARS-CoV helicase |
Investigator(s): |
Huang J, Sun H, Tanner JA, Watt RM |
Department: |
Biochemistry |
Source(s) of Funding: |
Research Fund for the Control of Infectious Diseases - Full Grants |
Start Date: |
02/2005 |
Abstract: |
We aim to fully dissect the mechanism of bismuth-mediated SCV helicase inhibition on the molecular level, focussing on the manner in which zinc, bismuth and RNA interact with the MBD. Through this work, we will garner a detailed understanding of the role played by the MbD and the way in which it modulates helicase activity, aiding our development of more effective bismuth drugs. |
Project Title: |
Biochemical characterization of a putative helicase from a novel coronavirus that causes pneumonia |
Investigator(s): |
Huang J, |
Department: |
Biochemistry |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
02/2005 |
Completion Date: |
01/2006 |
Abstract: |
This study will provide the foundation for drug discovery to prevent a SARS-like outbreak by the novel CoV-HKU1. Our special aims are: (1) Clone, express and purify the putative helicase from CoV-HKU1; (2) Determine whether this protein exhibits an NTPase activity, and whether the NTPase activity is stimulated by the presence of single stranded DNA or RNA oligomers; (3) Investigate the RNA and DNA-duplex unwinding activities of the purified protein to establish beyond doubt that it is the functional viral helicase of the CoV-HKU1. |
Project Title: |
Role of kinesin-mediated intracellular transportation in Alzheimer's Disease |
Investigator(s): |
Huang J |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2006 |
Abstract: |
N/A |
Project Title: |
Role of kinesin-mediated intracellular transportation in Alzheimer's Disease |
Investigator(s): |
Huang J, Song Y, Copeland NG, Jenkins NA, St George-Hyslop P, Westaway D, Wu W |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
01/2006 |
Abstract: |
(1) generation of mouse models with intracellular transport deficiency; (2) neuropathological analysis of the AD mouse models; (3) characterization of intracellular transportation in the mutant mice and primary cell cultures |
List of Research Outputs |
Bernini A., Spiga O., Venditti V., Prischi F., Bracci L., Huang J., Tanner J.A. and Niccolai N., Tertiary structure prediction of SARS coronavirus helicase, Biochem Biophys Res Commun. 2006, 343: 1101-1104. |
Ge R., Watt R.M., Sun X., Tanner J.A., He Q., Huang J. and Sun H., Expression and characterization of a histidine-rich protein, Hpn: potential for Ni2+ storage in Helicobacter pylori, Biochemical Journal. 2006, 393: 285-293. |
He M.L., Zheng B., Chen Y., Wong K.L., Huang J., Lin M.C., Peng Y., Yuen K.Y., Sung J.J. and Kung H.F., Kinetics and synergistic effects of siRNAs targeting structural and replicase genes of SARS-associated coronavirus., FEBS Letters. 2006, 580(10): 2414-2420. |
Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785. |
Lu L. and Huang J., Single-stranded oligonucleotide-mediated targeted gene repair in mammalian cells, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005. |
Peng Y., Yang P., Tanner J.A., Huang J., Li M., Lee H.H.F., Xu R.H., Kung H. and Lin M.C., Cold-inducible RNA binding protein is required for the expression of adhesion molecules and embryonic cell movement in Xenopus laevis, Biochem Biophys Res Commun. 2006, 344: 416-424. |
Wang J. and Huang J., Characterization of Intracellular Transportation in KbcU-Mutant Purkinje Cells., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005. |
Wang
Z. and Huang J., Mechanism
study on two DNA repair systems, 10th Research Postgraduate Symposium,
Faculty of Medicine, HKU, |
Yin W.X., Wu X.S., Li Z.H., Watt R.M., Huang J., Liu D.P. and Liang C.C., Targeted correction of a chromosomal point mutation by modified single-stranded oligonucleotides in a GFP recovery system, Biochemical and Biophysical Research Communications 334 (2005) 1032-1041. 2005. |
Zhang X., Chen B., Ng A.H.L., Tanner J.A., Tay D.K.C., So K.F., Rachel R.A., Copeland N.G., Jenkins N.A. and Huang J., Transgenic mice expressing cre-recombinase specifically in retinal rod bipolar neurons, Invest Ophthalmol Vis Sci. 2005, 46: 3515-20. |
Researcher
: Huen MSY |
List of Research Outputs |
Huen M.S.Y., A Mechanistic Study of Lambdaphage-Mediated Recombination in E. coli, PhD Thesis.. 2006. |
Researcher
: Hui KC |
List of Research Outputs |
Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Hui K.C., Ng P.K.M., Mak W.W., Jin D. and Song Y., Association of the cholesterol 24S-hydroxylase polymorphism with Alzheimer's disease in Chinese, HUGO 2006 Helsinki, Finland, 31 May-03 June 2006 . 2006. |
Researcher
: Jang BR |
List of Research Outputs |
Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42. |
Researcher
: Jim JJT |
List of Research Outputs |
Cheung K.M.C., Chen Y., Karppinen J., Chan D., Jim J.J.T., Luk K.D.K., Ala-Kokko L., Leong J.C.Y., Ott J., Sham P.C., Cheah K.S.E. and Song Y., Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in Chinese, Spine. 2006, 31(10): 1143-8. |
Cheung
K.M.C., Jim J.J.T.,
Noponen-Hietala N., Ott J., Karppinen
J., Sahraravand A., Luk K.D.K., Yip S.P.,
Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The Genetics of intervertebral
disc degenertation, European Cells and Material: ECM VI/SRN I Spinal
Motion Segment: From basic science to clinical application. |
Jim J.J.T., Noponen-Hietala N., Cheung K.M.C., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration, Spine. 2005, 30: 2735-2742. |
Researcher
: Jin D |
Project Title: |
Implementation of theoretical and technical system for disease genomics |
Investigator(s): |
Jin D |
Department: |
|
Source(s) of Funding: |
Matching Fund for National Key Basic Research Development Scheme (973 Projects) |
Start Date: |
08/2001 |
Abstract: |
To study implementation of theoretical and technical system for disease genomics. |
Project Title: |
Characterization of a novel centrosomal target of HTLV-I oncoprotein tax |
Investigator(s): |
Jin D |
Department: |
|
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
12/2001 |
Completion Date: |
11/2005 |
Abstract: |
To characterize a novel human centrosomal protein, which binds to HTLV-I oncoprotein Tax in yeast two-hybrid assay and co-immunoprecipitates with Tax from extracts of mammalian cells. |
Project Title: |
Mitotic checkpoint and genomic stability in ovarian cancer |
Investigator(s): |
Jin D |
Department: |
Biochemistry |
Source(s) of Funding: |
National Institutes of |
Start Date: |
09/2002 |
Abstract: |
To investigate the molecular basis of mitotic checkpoint in mammalian cells nad its relevance to genomic instability in ovarian cancer. |
Project Title: |
Functional characterization of a novel liver-enriched transcription factor of the bZIP family |
Investigator(s): |
Jin D, Chung SK, Ching YP, Ng IOL |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
12/2002 |
Abstract: |
Previous study of the research team shows that LZIP-[beta] is a liver-enriched transcription factor implicated in tissue-specific expression of genes. In this study, the team will focus on four areas of research:- 1) biochemical and biological characterization of LZIP-[beta] transcript and protein in mammalian tissues and cells; 2) functional characterization of LZIP-[beta] as a novel CRE-binding transcription factor; 3) investigating the roles of LZIP-[beta] in liver-specific gene expression and cancer development; and 4) establishment of frog and mouse models for functional studies of LZIP-[beta]. |
Project Title: |
Development of RNAi technology for inhibition of viral replication |
Investigator(s): |
Jin D |
Department: |
Biochemistry |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
11/2003 |
Completion Date: |
02/2007 |
Abstract: |
To use Sindbis virus as a model to systematically study RNAi-mediated inhibition of viral replication; to study the rules for selection of RNAi targets particularly effective for inhibition of viral replication in mammalian cells; to compare the effectiveness of siRNAs targeting UTR, non-structural (such as polymerase) or structural (such as capsid) regions. |
Project Title: |
Roles and regulation of peroxiredoxins: from yeast to human |
Investigator(s): |
Jin D |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
12/2003 |
Abstract: |
To perform in-depth analyses on the transcriptional regulation of yeast PMP20; to study the structure-function relationship of yeast and human peroxiredoxins; to characterize the impact of binding to heme on Tsa1p/Tsa2p function; to investigate the roles of peroxiredoxins in cell physiology and pathology. Out focus will be on apoptosis, aging and cell proliferation. |
Project Title: |
Roles and regulation of peroxiredoxins: from yeast to human |
Investigator(s): |
Jin D |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
12/2003 |
Abstract: |
N/A |
Project Title: |
Roles of spike protein in the pathogenesis of SARS coronavirus |
Investigator(s): |
Jin D, Zheng B |
Department: |
Biochemistry |
Source(s) of Funding: |
Research Fund for the Control of Infectious Diseases - Full Grants |
Start Date: |
02/2005 |
Abstract: |
To derive novel and important insights into the molecular mechanisms for SARS-CoV pathogenesis and to reveal novel strategies for prevention as well as therapeutic interventions of SARS |
Project Title: |
Regulatory roles for vault poly(ADP-ribose) polymerase in NF[kappa]B activation |
Investigator(s): |
Jin D, Yam JWP |
Department: |
Biochemistry |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
03/2005 |
Abstract: |
The main objectives of this project are: 1) To perform independent assays including co-immunoprecipitation and co-localization to verify the CIKS-VPARP interaction and to define the binding domains in the two proteins. 2) To document VPARP activation of NFkB using additional methods including EMSA and IKK assays. We will also determine the requirement for PARP activity in this activation. 3) To identify the relevant substrates or partners of VPARP that mediate its effect on NFkB. |
Project Title: |
Roles for p21-activated protein kinase 3 in HTLV-I pathogenesis |
Investigator(s): |
Jin D, Ching YP |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
01/2006 |
Abstract: |
To characterize the expression of Pak 3 in HTLV-I-transformed ATL cells; to study whether and how Tax induces Pak 3 expression and activity; to define the contributory roles of Pak 3 in Tax modulation of transcription and cell signaling; to assess the significance of Tax-Pak3 interaction in viral transformation and leukemogenesis. |
Project Title: |
Roles for p21-activated protein kinase 3 in HTLV-I pathogenesis |
Investigator(s): |
Jin D |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2006 |
Abstract: |
N/A |
Project Title: |
Gene regulatory function and cellular partners of SARS-associated coronavirus nucleocapsid protein |
Investigator(s): |
Jin D, Zheng B, Ching YP |
Department: |
Biochemistry |
Source(s) of Funding: |
Research Fund for the Control of Infectious Diseases - Full Grants |
Start Date: |
02/2006 |
Abstract: |
This project addressed fundamental questions on an important SARS-CoV structural protein. Our work may have implications in other aspects of SARS research. For one example, the activation of FGL2 has been thought to cause thrombosis in viral infection. Thus, elucidation of the influence of N protein on FGL2 may reveal a new mechanism for SARS-CoV pathogenesis. In addition, molecular dissection of the gene regulatory function of N protein and characterization of its cellular partners will help identify new targets for treatment. Finally, the biological systems and assays established might be used for drug screening. |
List of Research Outputs |
Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245. |
Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367. |
Chin
K.T., Wong C.M., Ng I.O.L. and Jin D., Functional characterization
of liver-enriched transcription factor CREB-H (poster 1989). , The
American Society for Cell Biology 45th Annual Meeting, |
Chin
K.T., Siu Y.T., Siu K.L. and Jin D., Tax-induced recruitment of
TORC family coactivators is required for transcriptional activation of the
human T-cell leukemia virus type 1 long terminal repeats (invited
discussant). , The Leukemia and Lymphoma Society's 2005 Stohlman Scholars
Symposium, Renaissance |
Ching
Y.P., Chan S.F. and Jin D., A centrosomal target of
human T-cell leukemia virus type I oncoprotein Tax on the road to genome
instability, The Croucher Advanced Study Institute “Signaling in Cell
Growth abd Differentiation”. The |
Choy E.Y.W., Kok K.H. and Jin D., Construction of New DNA Vectors Based on Promoters of Epstein-Barr Virus-Encoded Small RNAS For Expression of Small Hairpin RNAS in Mammalian Cells., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Choy E.Y.W., Kok K.H. and Jin D., Construction of new DNA vectors based on promoters of Epstein-Barr virus-encoded small RNAs for expression of small hairpin RNAs in mammalian cells., Cold Spring Harbor Laboratory 2005 Meeting on RNAi, Cold Spring Harbor, New York, USA, September 28 to October 2, 2005. . 2005. |
Deng J., Yang Y.L., Wang L.H., Jin D. and Liang G.D., Inhibition of the replication of Sindbis virus XJ-160 by RNAi., Chinese Journal of Microbiology and Immunology. 2005, 25: 496-500. |
Jin
D., A centrosomal target of HTLV-I
oncoprotein Tax on the road to genome instability., |
Jin D., Journal of RNAi and Gene Silencing (an international journal of biology and application of RNA interference), Editorial Board. LibPubMedia, 2005. |
Ko C.F., Yam J.W.P., Chan P.C.Y., Jin D. and Ng I.O.L., Interaction of deleted in liver cancer 1 (DLC1) with tensin2 and its implications in tumor suppression, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
Kok
K.H. and Jin D., Cell to
cell spreading of RNAi in mammalian cell, 10th Research Postgraduate
Symposium, Faculty of Medicine, HKU, |
Leung H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity, Proc Natl Acad Sci U S A. 2005, 102: 15207-15212. |
Leung T.H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in Liver Cancer 2, DLC2, Suppresses Cell Transformation via Inhibition of Rhoa Activity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Li H., Fung K.L., Jin D., Chung S.S.M., Cing Y.P., Ng I.O.L., Sze K.H., Ko C.B. and Sun H., Solution structures and dynamics of the sterile of Motif (SAM) domain of the deleted in liver cancer 2 (DLC2): a monomeric structure with membrane-binding properties, Croucher Foundation Advanced Study Institute: Advances in Protein Sciences, Biochemistry Department, The Chinese University of Hong Kong, Hong Kong, 15-17 December 2005 . 2005, PO-17, p.33. |
Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Hui K.C., Ng P.K.M., Mak W.W., Jin D. and Song Y., Association of the cholesterol 24S-hydroxylase polymorphism with Alzheimer's disease in Chinese, HUGO 2006 Helsinki, Finland, 31 May-03 June 2006 . 2006. |
Li Y. and Jin D., Genetic Variations of the Cholesterol Metabolism Pathway Genes and the risk of Alzheimer's Disease, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Ng K.M., Mak W., Jin D., st. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese. , Dement Geriatr Cogn Disord. 2006, 22: 399-404. |
Man C.W.Y., Rosa J., Wu Z.Q., Akira H., Jin D., Ling M.T., Cheung A., Kwong Y.L., Doxsey S. and Tsao G.S.W., ID1 Upregulates Aurora Kinase A, Induces Centrosome abnormalities, Polyploidy and Disrupts Microtubule Integrity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Man C.W.Y., Rosa J., Lee T.O., Lee H.Y.V., Chow B.K.C., Lo K.W., Doxsey S., Wu Z.G., Kwong Y.L., Jin D., Cheung A. and Tsao G.S.W., Latent membrane protein 1 suppresses RASSFIA expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells, Oncogene. 2006, 1-12. |
Ng D.C.H., Chan S.F., Kok K.H., Yam J.W.P., Ching Y.P., Ng I.O.L. and Jin D., Mitochondrial targeting of growth suppressor protein DLC2 through the START domain, FEBS Letters . 2006, 580(1): 191-8. |
Ng
M.H., Jin D. and Chan L.C., Ras Signalling in
Mll-Mediated Leukaemia, 10th Research Postgraduate Symposium, Faculty of
Medicine, HKU, |
Sze M.F., Ching Y.P., Jin D. and Ng I.O.L., Dysregulation of Mitotic Spindle Checkpoint Control in Hepatocellular Carcinomas , 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Wang X., Cheung H.W., Jin D., Ling M.T., Wong Y.C., Wang Q. and Tsao G.S.W., Effect of MAD2 expression on chemosensitivity to DNA damaging agent cisplatin in nasopharyngeal carcinoma cells., Proceeding NCRI Cancer conference, Birmingham, UK. 2005, 54. |
Wong C.M., Yam J.W.P., Ching Y.P., Yau T.O., Leung T.H.Y., Jin D. and Ng I.O.L., Rho GTPase-Activating Protein Deleted in Liver Cancer Suppresses Cell Proliferation and Invasion in Hepatocellular Carcinoma, Cancer Research. 2005, 65: 8861-8868. |
Wong H.L., Wang X., Chang R.C.C., Jin D., Feng H., Wang Q., Lo K.W., Huang D.P., Yuen P.W., Wong Y.C. and Tsao G.S.W., Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress., Molecular Carcinogenesis. 2005, 44: 92-101. |
Researcher
: Kok KH |
List of Research Outputs |
Choy E.Y.W., Kok K.H. and Jin D., Construction of New DNA Vectors Based on Promoters of Epstein-Barr Virus-Encoded Small RNAS For Expression of Small Hairpin RNAS in Mammalian Cells., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Choy E.Y.W., Kok K.H. and Jin D., Construction of new DNA vectors based on promoters of Epstein-Barr virus-encoded small RNAs for expression of small hairpin RNAs in mammalian cells., Cold Spring Harbor Laboratory 2005 Meeting on RNAi, Cold Spring Harbor, New York, USA, September 28 to October 2, 2005. . 2005. |
Kok
K.H. and Jin
D., Cell to cell spreading of RNAi in mammalian cell, 10th Research
Postgraduate Symposium, Faculty of Medicine, HKU, |
Ng D.C.H., Chan S.F., Kok K.H., Yam J.W.P., Ching Y.P., Ng I.O.L. and Jin D., Mitochondrial targeting of growth suppressor protein DLC2 through the START domain, FEBS Letters . 2006, 580(1): 191-8. |
Researcher
: Kwok JCF |
List of Research Outputs |
Lau J.W.K., Kwok J.C.F., Ng K.Y., Chan Y.S. and Shum D.K.Y., Developing vestibular neurons display altered commissural projections with depletion of chondroitin sulfates of the hindbrain matrix, Proceedings of the 28th Annual Meeting of Japan Neuroscience Society. 2005, P3–37. |
Researcher
: Lai WL |
List of Research Outputs |
Lai W.L. and Wong N.S., Regulation of GADD153 Expression at Post-transcriptional Level by ROS, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005. |
Researcher
: Lam VMS |
Project Title: |
Structural NADP+, subunit interaction and other stability determinants in human glucose-6-phosphate dehydrogenase (G6PD) and deficient variants |
Investigator(s): |
Lam VMS, Engel P.C., Adams M.J. |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
11/2000 |
Completion Date: |
09/2005 |
Abstract: |
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a global and local of jaundice in newborns. The majority are usually asymptomatic but environmental agents such as the ingestion of fava bean or some Chinese herbal medicines can induce favism or haemolysis. The project aims to bioengineer change(s) in the amino acids, around the 'structural' NADP site, some of which correspond to naturally occurring Class 1 variants. |
Project Title: |
The C-terminus of human glucose-6-phosphate dehydrogenase (h-G6PD): a structural and/or regulatory domain? |
Investigator(s): |
Lam VMS, Engel P.C., Adams M.J. |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
12/2002 |
Completion Date: |
09/2005 |
Abstract: |
The project aims at examining the role of the aromatic amino acids in the C-terminus. The research team will create a series of mutations in each of these residues, express and purify these enzymes for assay of stability and NADP+ binding. |
Project Title: |
'Structural' NADP+ and conformation change accompanying Glucose-6-phosphate dehydrogenase (G5PD) activity |
Investigator(s): |
Lam VMS, Au SWN |
Department: |
Biochemistry |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
01/2005 |
Completion Date: |
09/2005 |
Abstract: |
The main objectives of this project are: (1) use molecular biology techniques to create recombinant G6PD mutants at the catalytic site i.e., at His 263 and R393H & R393G near the 'structural' NADP; (2) use fluorimetric and spectrophotometric measurements to track the 'structural' NADP in mutant enzymes in (1) and compare with WT; (3) use sugar substrate analogues to form catalytically inactive enzyme-coenzyme sugar phosphate complexes. Use of this complex to assess the ability of G6P to promote reduction of the 'structural' NADP. Attempt to crystallise such enzyme ternary complexes and/or the mutant enzymes in (1). |
List of Research Outputs |
Researcher
: Law KFS |
List of Research Outputs |
Chan D., Gao B., Hu J.X., Law K.F.S., He L. and Cheah K.S.E., Abnormal Indian Hedgehog Signaling affects Distal Digit Patterning in a Mouse Model with Brachydactyly Type A1, Frontiers in Biomedical Research, The Univeristy of Hong Kong, Hong Kong, Dec 2. 2005. |
Researcher
: Law ML |
List of Research Outputs |
Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in Sox 10 mouse mutant, Mechanisms of Development. Elsevier, 2005, 122: S177. |
Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in a Sox10 mouse mutant generated by gene targeting , Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. |
Law
M.L., Tsang
W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the
Enteric Neural Crest Development, 10th Research Postgraduate Symposium,
Faculty of Medicine, HKU, |
Researcher
: Law ML |
List of Research Outputs |
Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in Sox 10 mouse mutant, Mechanisms of Development. Elsevier, 2005, 122: S177. |
Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in a Sox10 mouse mutant generated by gene targeting , Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. |
Law
M.L., Tsang
W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the
Enteric Neural Crest Development, 10th Research Postgraduate Symposium,
Faculty of Medicine, HKU, |
Researcher
: Lee YF |
List of Research Outputs |
Lee Y.F., Identifying the inner ear specific SOX2 regulatory element(s) and SOX2 regulation of MATH1, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005. |
Researcher
: Leong VYL |
List of Research Outputs |
Chan
D., Ho G., Leong V.Y.L. and Cheung K.M.C., The effect of severity of
disc degeration on mesenchymal stem cell's ability to regenerate the
intervertebral disc., European Cells and Material: ECM VI/SRN I Spinal
Motion Segment: From basic science to clinical application. |
Cheung
K.M.C., Ho G., Chan D. and Leong V.Y.L., regeneration of
nucleus pulposus after disectomy by autologous mesenchymal stem cells: a
rabbit model, European Cells and Material: ECM VI/SRN I Spinal Motion
Segment: From basic science to clinical application. |
Researcher
: Leung GWY |
List of Research Outputs |
Tong
H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the
Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific
Community - Stem Cells, Senescence and Cancer. |
Researcher
: Leung KKH |
List of Research Outputs |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006. |
Researcher
: Leung WL |
List of Research Outputs |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006. |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25. |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September . 2005. |
Leung W.L., Functional Analyses of Type IIA Procollagen in Embryo Development, PhD Thesis. 2006. |
Tong
H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the
RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of
Medicine, HKU, |
Researcher
: Leung YL |
Project Title: |
Molecular identity of nucleus pulposus cells in intervertebral disc |
Investigator(s): |
Leung YL, Cheung KMC, Chan D |
Department: |
Orthopaedics and Traumatology |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
12/2005 |
Abstract: |
1) Introduction: Low back pain has been a major focus in clinical practice. It represents a world-wide health problem of which about 70-80% population will experience low back pain in their lifetime [1,6]. Intervertebral disc degeneration has been suggested to associate with low back pain and sciatica and is thought to have multi-factorial causes. Previous study in human indicated that 90% of people will develop intervertebral disc degeneration above the age of 50. However, whether the degeneration is caused by natural aging or other unknown pathological conditions is still not clear [2]. Intervertebral discs (IVD) are avascular fibrocartilagenous structures between the vertebral bodies of the spine which function to articulate the spinal motion and are subject to high mechanical loading. Degeneration of IVD is generally characterized by changes in disc morphology, composition of extracellular matrix (ECM), loss of proteoglycan and water content, and an up-regulation of metalloproteinases in IVD [2,8-10]. Nonetheless, there is a lack of consensus on the cause of degeneration. In particular, whether the degeneration is a result from a loss of mechanical integrity in the disc or the mechanical loading itself being a precipitating factor of the degeneration is still controversial [6,7]. Studies have also suggested that the degeneration is related to a change of disc cells response to mechanical stimuli [11], but the molecular events happened during the response have not been clearly elaborated. IVD consists of three components: an outer fibrous ring (annulus fibrosus, AF), an inner gelatinous filling (nucleus pulposus, NP), and cartilaginous endplates (EP) which sandwich the former two structures. During organogenesis, NP is developed from the transformation of notochord and AF is differentiated from the condensation of sclerotome, implying that IVD is derived from mesodermal origin [3,4]. IVD is populated by three major cell types: chondrocytes in EP, notochordal/chondrocyte-like cells in NP and fibroblast-like cells in AF. NP and AF contain abundant ECM, particularly collagens and proteoglycans, which are present in different proportions in the two structures [6]. Cells in IVD have been defined base on their morphology, intercellular organization, and gene expression. NP is composed of a heterogeneous cell population of interconnected cells with prominent vacuoles, which are thought to be originated from the notochord, and small chondrocyte-like cells from yet unknown origin [12]. The notochordal cells appear to be replaced with chondrocyte-like cells during IVD maturation. The replacement of cells may be possibly due to apoptosis of notochordal cells together with an invasion of chondrocytes from AF or EP, or due to differentiation of notochordal cells into chondrocytic phenotype. Study has demonstrated that degeneration is not observed in IVD where notochordal cells persist to adult age, suggesting notochordal cells play vital role in maintaining IVD integrity [21]. Among various species studied, mature sheeps, dogs, and rats are suggested to retain NP cell populations mimicking those in adult humans [12]. In situ expression of variety of genes has been studies in NP. They express chondrocyte markers such as SOX9, collagen II and IX, agreccan, decorin, TGFbeta, and Ptc [13-18]. Gene knockout in mice has demonstrated that Sox5 and Sox6 regulate NP formation while Col2a1, Pax1/Pax9, Bapx1, and Jun play regulatory roles in the development of vertebral column [4,5,19,20]. To-date, the developmental regulation and specific function of NP in IVD are still largely unknown. In particular, there have been no genes found to be specifically expressed in the notochordal cells which can define their identity and distinguish them from chondrocyte-like cells in NP. 2) Key issues and problems: There has been limited advancement in the molecular biology of prenatal and postnatal IVD. Insufficient molecular characterization of IVD cells in is one of the major obstacles in understanding the properties of IVD and the etiology of disc degeneration. The lack of knowledge in NP cell-specific genes inevitably hampers the dissection of molecular pathways related to the IVD formation, maintenance, and the cause of IVD degeneration. On the other hand, we and other groups have been working on biological therapies such as the use of bioactive molecules and stem cells to regenerate disc cells in degenerated IVD. Without sufficient knowledge in the molecular signatures of the cells, accessing the outcome of the therapies will be difficult because cell phenotype in the treated IVD cannot be adequately described. In addition, the lack of cell-specific markers also compromises the use of high-throughput screening technologies that may rely on molecular cues to report expression changes specific to IVD. Taken together, the issue is critical to both basic and applied IVD research. 3) Hypothesis and objectives: It is hypothesized that notochordal cells in NP are specialized cells for IVD function and express unique genes which determine their specific differentiation status and cellular function. This study aims to identify the genes specifically expressed in notochordal cells in NP by the use of transcriptomics and bioinformatics. |
List of Research Outputs |
Researcher
: Li J |
List of Research Outputs |
Li J. and Cheah K.S.E., The role of Indian Hedgehog in chondrocyte hypertrophy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005. |
Researcher
: Li SKM |
List of Research Outputs |
Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785. |
Researcher
: Li X |
List of Research Outputs |
Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42. |
Researcher
: Li Y |
List of Research Outputs |
Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Hui K.C., Ng P.K.M., Mak W.W., Jin D. and Song Y., Association of the cholesterol 24S-hydroxylase polymorphism with Alzheimer's disease in Chinese, HUGO 2006 Helsinki, Finland, 31 May-03 June 2006 . 2006. |
Li Y. and Jin D., Genetic Variations of the Cholesterol Metabolism Pathway Genes and the risk of Alzheimer's Disease, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Ng K.M., Mak W., Jin D., st. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese. , Dement Geriatr Cogn Disord. 2006, 22: 399-404. |
Song Y., Ho W.L., Kwok H.H., Chu A.C.Y., Li Y. and Ho S.L., Genetic study of a large Chinese amyotrophic lateral sclerosis family., The 55th American society of Human Genetics meeting, October 25-29, 2005, Salt Lake City Utah, USA . 2005. |
Researcher
: Liu B |
List of Research Outputs |
Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785. |
Researcher
: Liu H |
List of Research Outputs |
Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42. |
Researcher
: Liu J |
List of Research Outputs |
Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42. |
Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y. S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57. |
Researcher
: Liu J |
List of Research Outputs |
Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42. |
Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57. |
Researcher
: Lo RLK |
List of Research Outputs |
Lo R.L.K., Ng V.C.W., Cheah K.S.E. and Chan D., ER-stress signaling and chondrocyte differentiation in mice, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005. |
Researcher
: Lu L |
List of Research Outputs |
Lu L. and Huang J., Single-stranded oligonucleotide-mediated targeted gene repair in mammalian cells, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005. |
Researcher
: Lui VCH |
Project Title: |
Cre-inducible disruption of Hedgehog signaling in neural crest cell: a novel approach to study roles of Hedgehog in enteric nerous system development |
Investigator(s): |
Lui VCH, Tam PKH, Sham MH |
Department: |
Surgery |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
11/2003 |
Abstract: |
To generate a DNA construct for Cre-inducible expression of a Ptc1[Delta]loop2 protein; to generate transgenic mice carrying the Ptc1[Delta]loop2 DNA construct by microinjection; transgenic mice will be crossed with a vagal NCC specific Cre mouse strain; to analysis of abnormal phenotypes in the devleoping ENS of the transgenic mutant mice. |
Project Title: |
Conditional knockout of Patched gene in enteric neural crest cells: functional study of the role of Hedgehog signaling in enteric nervous system development |
Investigator(s): |
Lui VCH, Tam PKH, Sham MH, Hui C.C. |
Department: |
Surgery |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
10/2004 |
Abstract: |
To cross floxed Ptc1 mice with a vagal NCC specific Cre mouse strain (b3-IIIa-cre); to analyze the abnormal phenotypes in the developing ENS of the transgenic mutant mice; to analyze the effects of mesenchyme-derived factors on NCCs of the transgenic mutant mice. |
Project Title: |
Investigation of Hoxb5 functions in enteric neurons in late gestation and neonatal period |
Investigator(s): |
Lui VCH, Sham MH, Tam PKH |
Department: |
Surgery |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
11/2004 |
Abstract: |
To investigate the functions of Homeobox gene Hoxb5 in enteric neurons. |
Project Title: |
Conditional knockout of Patched gene in enteric neural crest cells: functional study of the role of Hedgehog signaling in enteric nervous system development |
Investigator(s): |
Lui VCH |
Department: |
Surgery |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2005 |
Abstract: |
N/A |
Project Title: |
Functional analysis of Hoxb5 in enteric neurons in mice |
Investigator(s): |
Lui VCH |
Department: |
Surgery |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
11/2005 |
Abstract: |
N/A |
Project Title: |
Functional analysis of Hoxb5 in enteric neurons in mice |
Investigator(s): |
Lui VCH, Sham MH, Tam PKH |
Department: |
Surgery |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
11/2005 |
Abstract: |
To analyse the expression pattern of Hoxb5 protein in enteric neurons in postnatal and adult mice; to induce the expression of en-hoxb5 in enteric neurons in late stage of ENS development and shall analyse the phenotypic consequence of the perturbation of hoxb5 function in the ENS of postnatal and adult mice. |
List of Research Outputs |
Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the Enteric Neural Crest Development, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Researcher
: Ma RYM |
List of Research Outputs |
Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005. |
Tong
H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the
Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific
Community - Stem Cells, Senescence and Cancer. |
Tong
H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the
RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of
Medicine, HKU, |
Researcher
: Ma YMR |
List of Research Outputs |
Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022. |
Researcher
: Murphy G |
List of Research Outputs |
Chan W.Y., Cheah K.S.E., Ng V.C.W., Murphy G. and Chan D., Mouse model with impaired collagen X degradation at the chondro-osseous junction, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005. |
Researcher
: Ng AHL |
List of Research Outputs |
Ng A.H.L., Characterization of Cre expression in BAC-Pcp2-IRES-Cre Transgenic mice, MPhil Thesis. 2005. |
Zhang X., Chen B., Ng A.H.L., Tanner J.A., Tay D.K.C., So K.F., Rachel R.A., Copeland N.G., Jenkins N.A. and Huang J., Transgenic mice expressing cre-recombinase specifically in retinal rod bipolar neurons, Invest Ophthalmol Vis Sci. 2005, 46: 3515-20. |
Researcher
: Ng DCH |
List of Research Outputs |
Ng D.C.H., Chan S.F., Kok K.H., Yam J.W.P., Ching Y.P., Ng I.O.L. and Jin D., Mitochondrial targeting of growth suppressor protein DLC2 through the START domain, FEBS Letters . 2006, 580(1): 191-8. |
Researcher
: Ng VCW |
List of Research Outputs |
Chan W.Y., Cheah K.S.E., Ng V.C.W., Murphy G. and Chan D., Mouse model with impaired collagen X degradation at the chondro-osseous junction, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005. |
Lo R.L.K., Ng V.C.W., Cheah K.S.E. and Chan D., ER-stress signaling and chondrocyte differentiation in mice, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005. |
Researcher
: Ott J |
List of Research Outputs |
Cheung
K.M.C., Jim J.J.T., Noponen-Hietala
N., Ott J., Karppinen J.,
Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The Genetics of intervertebral
disc degenertation, European Cells and Material: ECM VI/SRN I Spinal
Motion Segment: From basic science to clinical application. |
Researcher
: Poon WH |
List of Research Outputs |
Wong N.S. and Poon W.H., The Kappa-opioid receptor specific agonist U50488H induces mitochondrial stress in cultured human cancer cells., The FEBS Journal (formerly European Journal of Biochemistry). 2005, 272, Supplement 1: n5-029p. |
Researcher
: Sae-Pang JJ |
List of Research Outputs |
Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005. |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Researcher
: Sham MH |
Project Title: |
Hoxb3lacZ: a mutant mouse model for studying the roles of Hoxb3 in heart and thoracic body wall development |
Investigator(s): |
Sham MH |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
09/2003 |
Abstract: |
To characterize the Hoxb3(lacZ) mutant locus and examine if this is a hypomorphic mutant; to analyse the cardiac abnormalities in the Hoxb3(lacZ) mutant using molecular markers and determine the role of Hoxb3 during heart development; to examine the ventral body wall defect by morphological and molecular markers, and identify any cooperation of Hoxb3 with other Hox genes in the developmental processes involved. |
Project Title: |
Hoxb3lacZ: a mutant mouse model for studying the roles of Hoxb3 in heart and thoracic body wall development |
Investigator(s): |
Sham MH |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
09/2003 |
Abstract: |
N/A |
Project Title: |
Investigating the molecular basis of Sox10 functions in enteric nervous system development using a series of mutant mouse models |
Investigator(s): |
Sham MH |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
09/2005 |
Abstract: |
N/A |
List of Research Outputs |
Cai
K., Xu R. and Sham M.H.,
Adeno-associated virus vector-mediated angiogenic inhibitors suppress lung
tumor growth in mice., 10th Research Postgraduate Symposium, Faculty of
Medicine, HKU, |
Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. |
Kong
C.T., Sham M.H. and Chan L.C., The MLL-EEN fusion gene leads
to maturation arrest and self-renewal of hematopoietic progenitors in ES
cells and the development of myeloid leukemia in chimeric mice, FASEB
Summer Research Conferences - Hematological Malignancies, Saxtons River, USA.
July 30 - |
Kong C.T., Sham M.H., So C.W.E., Cheah K.S.E., Chen S.J. and Chan L.C., The Mll-Een knockin fusion gene enhances proliferation of myeloid progenitors derived from mouse embryonic stem cells and causes myeloid leukaemia in chimeric mice, Leukemia. 2006, 20: 1829–1839. |
Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in Sox 10 mouse mutant, Mechanisms of Development. Elsevier, 2005, 122: S177. |
Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in a Sox10 mouse mutant generated by gene targeting , Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. |
Law
M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the
Enteric Neural Crest Development, 10th Research Postgraduate Symposium,
Faculty of Medicine, HKU, |
Lui V.C.H., Fu M., Poon H.C., Sham M.H., Pachnis V., Hui C.C. and Tam P.K.H., Conditional knockout of PTC1 gene in vagal neural crest cells causes defective ENS development in mice, Development of the Enteric Nervous System: Cells, signals and genes, New York, U.S.A., 26-29 March 2006. 2006. |
Lui
V.C.H., Cheng W.C., Chen Y., Sham M.H. and Tam P.K.H., Homeobox gene HOXB5 is
required in the embryonic development of the enteric nervous system, 52nd
Annual International Congress of British Association of Paediatric Surgeons, |
Lui V.C.H., Cheng W.C., Chen Y., Sham M.H. and Tam P.K.H., Perturbation of Hoxb5 signalling in vagal neural crest cells causes defective development of the enteric nervous system, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September 2005. |
Lui V.C.H., Cheng W.C., Chen Y., Sham M.H. and Tam P.K.H., Perturbation of Hoxb5 signalling in vagal neural crest cells causes defective development of the enteric nervous system, Mechanisms of Development. 2005, 122: S93. |
Ngan E.S.W., Lui V.C.H., Lau K.C., Garcia-Barcelo M.M., Sham M.H. and Tam P.K.H., Transcriptional profiling of enteric neural crest cells, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September 2005. |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005. |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Sham
M.H., Ectopic expression of Hoxb3 in the
mouse hindbrain causes abnormal ear development, The 15th International
Society of Development Biologists Congress, |
Sham
M.H., Sox10 mutations and enteric nervous system
development, Department of Anatomy and Cell Biology, |
Siu
K.Y., Sham M.H. and Chow B.K.C., Secretin is widely
expressed during mouse embryonic development, 7th International Symposium
on VIP, PACAP and Related Peptides, |
Siu K.Y., Sham M.H. and Chow B.K.C., Secretin is widely expressed during mouse embryonic development, Regulatory Peptides. 2006, 130(3): 176. |
Siu K.Y., Sham M.H. and Chow B.K.C., The prenatal expression of secretin receptor, Annals New York Academy of Sciences. 2006, 1070: p561-565. |
Wong E.Y.M., Chan Y.S., Wu D.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in mouse hindbrain causes abnormal ear development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September . 2005. |
Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia . 2005. |
Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Hoxb3 is involved in the endothelin-1 signaling pathway in patterning the facial branchial arches, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005. |
Wong P.M., Lu L. and Sham M.H., HOXB3 Mutation Generated By Gene Targeting Leads to Plasmacytoma, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Xu R.,
Ma H., Li H., Sham M.H., Li E.T.S., Tam P.K.H. and Lam K.S.L., Oral viral vector gene
delivery, In: Redberry GW (ed). Trends in Gene Therapy Research. |
Researcher
: Sham PC |
Project Title: |
An association screen for schizophrenia susceptibility loci in a high-LD, gene-rich region of chromosome 3p |
Investigator(s): |
Sham PC |
Department: |
Psychiatry |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
07/2004 |
Abstract: |
To identify novel susceptibility loci for schizophrenia, by conducting a high-density SNP screen of a region recently identified by a meta-analysis of 20 genome-wide linkage scans. |
Project Title: |
A systematic screen for schizophrenia susceptibility loci in high-LD, gene-rich chromosomal regions implicated by meta-analysis of whole genome linkage scans |
Investigator(s): |
Sham PC |
Department: |
Psychiatry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2006 |
Abstract: |
N/A |
Project Title: |
A systematic screen for schizophrenia susceptibility loci in high-LD, gene-rich chromosomal regions implicated by meta-analysis of whole genome linkage scans |
Investigator(s): |
Sham PC, Chen RYL, Ng KP, Li T |
Department: |
Psychiatry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
01/2006 |
Abstract: |
To identify novel susceptibility loci for
schizophrenia, by conducting a high-density SNP screen of a number of
chromosomal regions that are (a) identified as linkage hotspots by a recent
meta-analysis of 20 genome-wide scans of schizophrenia, (b) gene-rich and (c)
high in the level of linkage disequilibrium (LD). Optimal marker sets that
tag all common variation in these regions will be selected using HapMap data
on the Chinese population. These regions will be screened in 489 cases of
DSM-IV schizophrenia and 520 controls recruited from |
List of Research Outputs |
Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S.P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on familial Early-onset Degenerative Disc Disease(DDD), Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland.. 2006. |
Researcher
: Shum DKY |
Project Title: |
Expression of heparanase in the injured spinal cord |
Investigator(s): |
Shum DKY |
Department: |
Biochemistry |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
11/2003 |
Abstract: |
To determine the time course and cellular source of heparanase expression in the bridged hemicord; to determine the distribution of substrate HS in relation to the heparanase-expressing cells. |
Project Title: |
Expression of chondroitin sulfotransferases in the injured spinal cord |
Investigator(s): |
Shum DKY |
Department: |
Biochemistry |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
11/2004 |
Abstract: |
To determine the expression profiles of the chondroitin sulfotransferases (STs) with time; to map the expression of chondroitin STs in reactive astrocytes, macrophages and meningeal fibroblasts that invade the leison site; to recover chondroitin sulfates of the lesion site and surrounding glial scar for comparison of sulfation patterns with those of intact tissue. |
Project Title: |
Chondroitin sulfates regulate axonal growth and patterning in the developing hindbrain |
Investigator(s): |
Shum DKY |
Department: |
Biochemistry |
Source(s) of Funding: |
Incentive Award for RGC CERG Fundable But Not Funded Projects |
Start Date: |
07/2005 |
Completion Date: |
06/2006 |
Abstract: |
N/A |
List of Research Outputs |
Chan C.H., Ip M.S.M. and Shum D.K.Y., Heparan Sulfate/Syndecan-1 Modulates the Balance between Proteinase and Anti-Proteinase in Bronchiectasis, Proteoglycans in Signaling Stockholm (Runo), Sweden, September 7-11,2005. |
Chen L.W., Tse Y.C., Li C., Guan Z.L., Lai C.H., Yung K.K.L., Shum D.K.Y. and Chan Y.S., Differential expression of NMDA and AMPA/KA receptor subunits in the inferior olive of postnatal rats. , Brain Research. 2006, 1067(1): 103-114. |
Lai S.K., Lai C.H., Yung K.K., Shum D.K.Y. and Chan Y.S., Maturation of otolith-related brainstem neurons in the detection of vertical linear acceleration in rats. , Eur J Neurosci.. 2006, 23(9): 2431-46. |
Lau J.W.K., Kwok J.C.F., Ng K.Y., Chan Y.S. and Shum D.K.Y., Developing vestibular commissural projections display differential patterns with chondroitinase treatment of the hindbrain, Society for Neuroscience Abstract (U.S.A.). 2005, 481.8. |
Lau J.W.K., Kwok J.C.F., Ng K.Y., Chan Y.S. and Shum D.K.Y., Developing vestibular neurons display altered commissural projections with depletion of chondroitin sulfates of the hindbrain matrix, Proceedings of the 28th Annual Meeting of Japan Neuroscience Society. 2005, P3–37. |
Li C., Zhang Y. K., Guan Z.L., Shum D.K.Y. and Chan Y.S., Vestibular afferent innervation in the vestibular efferent nucleus of rats. , Neurosci Lett.. 2005, 385(1): 36-40. |
Liu J., Chau C.H., Liu H., Jang B.R., Li X., Chan Y.S. and Shum D.K.Y., Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. , J Cell Sci.. 2006, 119(Pt 6): 933-42. |
Yeung
M.N., Zhou Z., Chan D. and Shum D.K.Y., Expression of heparanase
in newborn mouse growth plates, Glycoconjugate Journal, GlycoXVIII, XVIII
International Symposium on Glycoconjugates, |
Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan Sulfates and Heparanase in the Mineralizing Matrix of Developing Mouse Growth Plate., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Yeung
M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan sulfates and
heparanase at the mineralization front of the developing growth plate., Proteoglycans
in Signaling, |
Zhang F.X., Lai C.H., Tse Y.C., Shum D.K.Y. and Chan Y.S., Expression of Trk receptors in otolith-related neurons in the vestibular nucleus of rats., Brain Research. 2005, 1062(1-2): 92-100. |
Zhang F.X., Lai C.H., Li J.L., Shum D.K.Y. and Chan Y.S., Tyrosine kinase receptor immunoreactivity in trigeminal mesencephalic and motor neurons following transection of masseteric nerve of the rat. , Neuroscience. 2006, 139(3): 921-30. |
Zhang
Y. and Shum D.K.Y.,
Functional Study of Heparanase in the explant cultures of rat dorsal root
ganglia., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, |
Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57. |
Researcher
: Siu KL |
List of Research Outputs |
Chin
K.T., Siu Y.T., Siu K.L. and Jin D., Tax-induced recruitment of TORC
family coactivators is required for transcriptional activation of the human
T-cell leukemia virus type 1 long terminal repeats (invited discussant). , The
Leukemia and Lymphoma Society's 2005 Stohlman Scholars Symposium, Renaissance
|
List of Research Outputs |
Chin K.T., Siu Y.T., Siu K.L. and Jin D., Tax-induced recruitment of TORC family coactivators is required for transcriptional activation of the human T-cell leukemia virus type 1 long terminal repeats (invited discussant). , The Leukemia and Lymphoma Society's 2005 Stohlman Scholars Symposium, Renaissance Scottsdale Resort, Arizona, USA, September 23-24, 2005. . 2005. |
Researcher
: Smith DK |
Project Title: |
Patterns in proteins with unusual flexibility profiles |
Investigator(s): |
Smith DK |
Department: |
Biochemistry |
Source(s) of Funding: |
Seed Funding for New Staff |
Start Date: |
08/2002 |
Abstract: |
To identify what makes some proteins imcompatible with flexibility parameters calculated from a large set of protein structures. |
List of Research Outputs |
Cai J.J., Smith D.K., Xia X. and Yuen K.Y., MBEToolbox 2.0: an enhanced version of a Matlab toolbox for Molecular Biology and Evolution., Evolutionary Bioinformatics Online. 2006, 2: 187-190. |
Fu W., Chung B.H.Y., Smith D.K. and Cheung P.T., Automated method for the identification of conserved non-coding regions in hypoxic-ischaemic regulated genes in different species, DK 50th Anniversary Symposium on Paediatric Neurology and Neuro-Rehabilitation, 16-17 September 2005. |
Fu W., Chung B.H.Y. and Smith D.K., Bioinformatic Pipeline for the Identification of Transciption Factor Binding Sites in Mouse and Human, Human Genome Meeting (HGM) 2006, Helsinki, Finland, 31 May - 3 June 2006. 59. |
Fu W., Chung B.H.Y., Smith D.K. and Cheung P.T., Bioinformatic piepline for the identification of transcription factor binding sites in mouse and human, Joint 6th Human Genome Organization (HUGO) Pacific Meeting & 7th Asia-Pacific Human Genetics Conference (HUGO-AP 2006), Taipei, Taiwan, 6-10 March 2006. 93. |
Fu W., Chung B.H.Y., Smith D.K. and Cheung P.T., Bioinformatic pipeline for the identification of transcription factor binding sites in mouse and human, Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association, Queen Elizabeth Hospital, 7 January 2006. 58. |
Fu W., Chung B.H.Y., Chan K.W., Bhatia I., Smith D.K. and Cheung P.T., Sequence analysis for putative transcription factor binding sites of a novel hypoxic-ischaemic regulated gene - HID-1, Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association, Queen Elizabeth Hospital, 7 January 2006. 61. |
Fu W., Chung B.H.Y., Chan K.W., Bhatia I., Smith D.K. and Cheung P.T., Sequence analysis of putative promoter sequences of known and novel genes identified by hpoxic-ischaemic insult, 10th Research Postgraduate Symposium , Faculty of Medicine, HKU, 3 December 2005. 118. |
He W., Gong K., Smith D.K. and IP N.Y., The N-terminal cytokine binding domain of LIFR is required for CNTF binding and signaling ., FEBS Letters. 2005, 579: 4317-4323. |
Researcher
: So CL |
List of Research Outputs |
Chan
D., Tsang K.Y., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B.,
Yamada Y., Bateman J.F., Cheung K.M.C.
and Cheah K.S.E., Endoplasmic
reticulum stress and reprogramming of hypertrophic chondrocytes, Gordon
Research Conference: Collagen. |
Tsang
K.Y., Chan D., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B.,
Yamada Y., Bateman J.F., Cheung K.M.C.
and Cheah K.S.E., Chondroctes
Alleviate ER Stress Caused by Unfolded Proteins by Reprogramming, The
British Society for Matrix Biology. 25th Anniversary Meeting Pathobiology of
Bone and Cartilage. |
Researcher
: Song Y |
Project Title: |
Genetic linkage analysis of early onset degenerative disc disease in Southern Chinese |
Investigator(s): |
Song Y, Cheah KSE, Cheung KMC, Leong JCY, Chan D |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
11/2003 |
Abstract: |
To detect linkage associated with early onset familial DDD by performing a genome-wide scan; to define the chromosomal location of the early onset familial DDD gene; to begin preliminary work towards positional/candidate clonning. |
Project Title: |
Genetic linkage analysis of early onset degenerative disc disease in Southern Chinese |
Investigator(s): |
Song Y, Cheah KSE, Cheung KMC, Leong JCY, Chan D |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
11/2003 |
Abstract: |
N/A |
Project Title: |
Genetic study of Alzheimer disease in Chinese |
Investigator(s): |
Song Y, Sham PC, |
Department: |
Genome Research Centre |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
01/2005 |
Completion Date: |
06/2006 |
Abstract: |
The main objectives of the project are: 1) To establish the methodology for genome-wide association analysis using pooled DNA samples and the Affymetrix 100k GeneChip at the Genome Research Centre, so that this can be provided as a service to investigators. 2) To detect novel susceptibility loci for Alzheimer's disease using this methodology. |
Project Title: |
Mapping and cloning a new gene on chromosome 8q24 for amyotrophic lateral sclerosis in a large Chinese family |
Investigator(s): |
Song Y |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2005 |
Abstract: |
N/A |
Project Title: |
Mapping and cloning a new gene on chromosome 8q24 for amyotrophic lateral sclerosis in a large Chinese family |
Investigator(s): |
Song Y, Ho SL, Fong CY, Ramsden D.B. |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
01/2005 |
Abstract: |
Biomarkers detection; detection possible ALS modifier on chromosome 10 in Branch A; longitudinal follow-up of both branches; mapping the CMT II locus in Branch B. |
Project Title: |
Mapping a genetic modifier for heart defects in Type IIA procollagen deficient mutant mice |
Investigator(s): |
Song Y |
Department: |
Genome Research Centre |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2006 |
Abstract: |
N/A |
Project Title: |
Mapping a genetic modifier for heart defects in Type IIA procollagen deficient mutant mice |
Investigator(s): |
Song Y, Cheah KSE, Sham PC |
Department: |
Genome Research Centre |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
01/2006 |
Abstract: |
To perform a genome-wide scan using mouse microsatellite markers to map the modifer locus to within a 20cM region; to generate region-specific speed modifer congenic mice for fine mapping of this 20cM region; to map the modifier locus to a 1cM region and combine with the results of gene expression in the modifier region to provide the essential genetic resources for future studies aimed at precise identification of the modifier gene. |
List of Research Outputs |
Chai
L., Leung W.K., Zee K.Y. and Song Y., Association Between Genetic
Polymorphisms and Periodontitis In Hong Kong Population., A Preliminary
Report. 84th International association for Dental Research, June 28 - |
Cheung K.M.C., Chen Y., Karppinen J., Chan D., Jim J.J.T., Luk K.D.K., Ala-Kokko L., Leong J.C.Y., Ott J., Sham P.C., Cheah K.S.E. and Song Y., Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in Chinese, Spine. 2006, 31(10): 1143-8. |
Cheung
K.M.C., Jim J.J.T.,
Noponen-Hietala N., Ott J., Karppinen
J., Sahraravand A., Luk K.D.K., Yip S.P.,
Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The Genetics of intervertebral
disc degenertation, European Cells and Material: ECM VI/SRN I Spinal
Motion Segment: From basic science to clinical application. |
Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S.P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage Analysis on familial Early-onset Degenerative Disc Disease(DDD), Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland.. 2006. |
Jim J.J.T., Noponen-Hietala N., Cheung K.M.C., Ott J., Karppinen J., Sahraravand A., Luk K.D.K., Yip S.P., Sham P.C., Song Y., Leong J.C.Y., Cheah K.S.E., Ala-Kokko L. and Chan D., The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration, Spine. 2005, 30: 2735-2742. |
Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Hui K.C., Ng P.K.M., Mak W.W., Jin D. and Song Y., Association of the cholesterol 24S-hydroxylase polymorphism with Alzheimer's disease in Chinese, HUGO 2006 Helsinki, Finland, 31 May-03 June 2006 . 2006. |
Li Y., Leung W.C.W., Chen Y., Cheung B.M.Y., Liang R.Y.H., Yik P.Y., Ng K.M., Mak W., Jin D., st. George-Hyslop P. and Song Y., Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese. , Dement Geriatr Cogn Disord. 2006, 22: 399-404. |
Meng Y., Rogaeva E., Lee J.H., Gu Y.J.,
Kawarai T., Katayama T., Erlich P., Baldwin C.T., Cheng R., Hasegawa H., Chen
F., Shibata N., Lunetta K.L., Cupples L.A., Song Y., Fraser P.E., Westaway D.,
Mayeux R., Farrer L.A. and St. George-Hyslop P., The sortilin-related
recentor SORLA is functionally and genetically associated with Alzheimer
Disease., The 55th american society of Human Genetics meeting.
October25-29, 2005, |
Ng M.C., Ho J.T., Ho S.L., Lee R., Li G., Song Y., Chan K.H., Cheng T.S., Yang E.S. and
Leong L.Y., Asymptomatic members with SOD1 mutation in a large kindred with
familial amyotrophic lateral sclerosis have abnormal water diffusion
characterisitcs., The International Society for Magnetic Resonance in
Medicine (ISMRM2006). 6-12 May 2006, |
Song Y., Ho D.W.H., Cheung K.M.C., Karppinen J., YIP S.P., Leong J.C.Y., Ott J., Luk K.D.K., Cheah K.S.E., Sham P.C. and Chan D., Genetic Linkage analysis of early onset degenerative disc disease in Southern Chinese., HUGO Pacific meeting & Asia-pacific Human Genetics Conference (HUGO-AP 2006), March 6-10, 2006 Academica Sinica, Taipei. 2006. |
Song Y., Ho W.L., Kwok H.H., Chu A.C.Y., Li Y. and Ho S.L., Genetic study of a large Chinese amyotrophic lateral sclerosis family., The 55th American society of Human Genetics meeting, October 25-29, 2005, Salt Lake City Utah, USA . 2005. |
Tang L.F., Chan S.Y., Sham P.C. and Song Y., In silico mapping of quantitative trait loci affecting bone mineral density in mice., HUGO Pacific meeting & Asia-Pacific Human Genetics Conference (HUGO-AP 2006) March 6-10,2006 Academica Sinica, Taipei. 2006. |
Tsui L.C., Mak W., Sham P.C., Song Y. and Tam P.K.H., Haplotype Map of the Human Genome, Nature . 2005, 437: 1299-1320. |
Researcher
: Tai CP |
List of Research Outputs |
Tai C.P., An In VivoAnalysis of Specificity of Gene Transactivation by SOX Proteins, PhD Thesis. 2006. |
Researcher
: Tam PKH |
Project Title: |
Transgenesis animals as bioreactors: production of a new immunosuppressive protein CTLA4Ig by transgenesis |
Investigator(s): |
Tam PKH, |
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 |
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, Zhang J.Z., Wang W.L., Shi C.R. |
Department: |
Surgery |
Source(s) of Funding: |
S.K. Yee Medical Foundation - General Award |
Start Date: |
10/2000 |
Abstract: |
To improve the standard of surgical care of children in China through the consolidation and expansion of a scheme of "Train-the-Trainers"; to improve our understanding of special paediatric surgical issues relevant to the Chinese population (e.g. disease patterns, transferability of western "advances" to China etc) through systematic exchanges with major centres in China and hence enhance our ability to deliver better surgical care to children in Hong Kong; to promote modern concepts of medical education among leaders of the new generation of doctors through the introduction of structured training, problem-based learning, life-long learning, and the use of evidence-based medicine and information technology. |
Project Title: |
Sonic hedgehog signalling in chronic allograft rejection |
Investigator(s): |
Tam PKH, Tian L, Dallman M.J., Lamb J.R. |
Department: |
Surgery |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
09/2002 |
Completion Date: |
08/2005 |
Abstract: |
To investigates the role of Notch, Sonic hedgehog (Shh) signalling in acute and chronic graft rejection in a rat model of small bowel transplantation; to study if the blockade of Shh signalling alone or in conjunction with the use of TFG-[beta] inhibitors can ameliorate chronic rejection. |
Project Title: |
The role of sonic hedgehog in immune system |
Investigator(s): |
Tam PKH, Tian L, Chan VSF, Lamb J.R. |
Department: |
Surgery |
Source(s) of Funding: |
Other Funding Scheme |
Start Date: |
10/2002 |
Abstract: |
To elucidate the role of sonic hedgehog in CD4+ T cells activation and to identify its downstream targets suring T cell activation. |
Project Title: |
Improving the survival and quality of life of children with cancers in China |
Investigator(s): |
Tam PKH, Wong IHN, Chan GCF, Ren Y, Lin CL, Li Z.Z., Zhang J.Z., Wang W.L., Shi C.R. |
Department: |
Surgery |
Source(s) of Funding: |
S.K. Yee Medical Foundation - General Award |
Start Date: |
10/2003 |
Abstract: |
To improve the survival and quality of life of poor and sick children suffering from cancer through the establishment of a Chinese Children Cancer Consortium which will be responsible for the introduction and implementation of modern, comprehensive management protocols, and for training and educating health care workers around the country to adopt the new standard of cares for children with cancer. |
Project Title: |
The study of co-stimulatory function of sonic hedgehog in CD4+ lymphocytes |
Investigator(s): |
Tam PKH, Chan VSF, Lamb J.R. |
Department: |
Surgery |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
11/2003 |
Abstract: |
To study the distribution of Shh and its receptors on the surface of T cells during T cell activation; to study the effect of Shh on TH1 and TH2 cell differentiation; to identify the downstream targets of Shh signaling pathway in CD4+ T lymphocytes. |
Project Title: |
Evaluation of HOXB5 as a new Hirschprung's disease susceptibility locus |
Investigator(s): |
Tam PKH, Lui VCH, Garcia-Barcelo MM |
Department: |
Surgery |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
11/2004 |
Abstract: |
To evaluate the human HOXB5 gene as a new Hirschsprung's disease susceptibility locus. |
Project Title: |
Further
expansion of the "Train-the-Trainers" programme for paediatric
surgery in |
Investigator(s): |
Tam PKH, Wong KKY, Chan KL, Yip KF, Wang W.L., Shi C.R., Zhang J.Z., Zhan JH, Jin XQ |
Department: |
Surgery |
Source(s) of Funding: |
S.K. Yee Medical Foundation - General Award |
Start Date: |
05/2005 |
Abstract: |
The project aims to improve the standard
of surgical care of children in |
Project Title: |
University strategic research theme: Genomics, Proteomics & Bioinformatics |
Investigator(s): |
Tam PKH, Leung FCC, Chen SF, Che CM, He Q, Ng KP |
Department: |
Surgery |
Source(s) of Funding: |
Seed Funding for Strategic Research Theme |
Start Date: |
05/2005 |
Abstract: |
To facilitate multidisciplinary research in the areas of genomics, proteomics and bioinformatics. The three subthemes would be created, and an additional subtheme on thical, legal and social issues (ELSI) should be created. |
List of Research Outputs |
Tsui L.C., Mak W., Sham P.C., Song Y. and Tam P.K.H., Haplotype Map of the Human Genome, Nature . 2005, 437: 1299-1320. |
Researcher
: Tam PPL |
List of Research Outputs |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25. |
Researcher
: Tam S |
List of Research Outputs |
Cheung Y.F., Karmin O., Tam S. and Siow Y.L., Induction of MCP1, CCR2, and iNOS Expression in THP-1 Macrophages by Serum of Children Late After Kawasaki Disease, Pediatric Research. 2005, 58(6): 1306-1310. |
Cheung Y.F., Karmin O., Tam S. and Siow Y.L., MCP1, CCR2 and iNOS Induction in THP-1 Macrophages by Serum of Children Late After Kawasaki Disease, 1st Congress of Asian Society for Pediatric Research, Tokyo, Japan, 24-26 November 2005. 91. |
Researcher
: Tam SMT |
List of Research Outputs |
Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022. |
Researcher
: Tam TSM |
List of Research Outputs |
Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005. |
Researcher
: Tang LF |
List of Research Outputs |
Tang L.F., Chan S.Y., Sham P.C. and Song Y., In silico mapping of quantitative trait loci affecting bone mineral density in mice., HUGO Pacific meeting & Asia-Pacific Human Genetics Conference (HUGO-AP 2006) March 6-10,2006 Academica Sinica, Taipei. 2006. |
Researcher
: Tanner JA |
Project Title: |
Comparative Characterization of the Two Polyphosphate Kinases of M. tuberculosis |
Investigator(s): |
Tanner JA |
Department: |
Biochemistry |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
02/2005 |
Abstract: |
Inorganic polyphosphate (polyP) is present in every cell in nature and consists of chains of tens or hundreds of orthophosphate residues linked by high-energy phospoanhydride bonds. For decades, the molecule was ignored as a 'molecular fossil', but recent discoveries, principally by Nobel Prize winner Arthur Kornberg, have challenged this view and brought deserved attention to this forgotten biopolymer [1]. In prokaryotes, the molecule plays a critical role in physiological adjustments to growth, development, stress and deprivation [2], besides acting as a phosphate reservoir, a metal chelator, a buffer, and is an important factor in mRNA processing and degradadation. In eukaryotes, roles have only started to be uncovered in the last year or two, but the molecule has already been shown to be a regulatory factor in the proliferative signaling pathways of mammalian cells [3]. It is clear that this simple inorganic molecule plays fundamental and crucial roles that are only just beginning to be unravelled. Until 2002, it was believed that polyphosphates were synthesized by a single class of enzymes, the polyphosphate kinases (PPK). However, a landmark paper from Kornberg in 2002 challenged that view [4], and it was discovered that there are in fact two classes of polyphosphate synthetases in prokaryotes: PPK1 and PPK2. Some bacteria, such as E. coli and H. pylori, only possess PPK1, others, such as M. tuberculosis, have both PPK1 and PPK2, whilst a few others only have PPK2. As PPK1 and PPK2 only exist in microorganisms and are absolutely absent from higher eukaryotes, these are excellent targets for new classes of antibacterials. As a first step towards both new antibacterials against tuberculosis and to deepen our understanding of this fundamental class of enzymes, we here propose to purify and perform a comparative characterization of PPK1 and PPK2 from M. tuberculosis. We shall test the emerging hypothesis that PPK1 is primarily a Mg2+-dependent ATP driven kinase whilst PPK2 is primarily a Mn2+-dependent GTP driven kinase. If this hypothesis holds true, it carries significant insight into the relationship between inorganic polyphosphate and the cell cycle.We can break down the overall objectives of this seed project funding grant into a three-stage process:I. Cloning of the ppk1 and ppk2 genes from M. tuberculosis.II. Purification of the PPK1 and PPK2 proteins.III. Comparative enzymatic characterization of PPK1 and PPK2.1. Kornberg, A., N. N. Rao, et al. (1999). "Inorganic polyphosphate: a molecule of many functions." Annu Rev Biochem 68: 89-125.2. Kuroda, A., K. Nomura, et al. (2001). "Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E. coli." Science 293(5530): 705-8.3. Wang, L., C. D. Fraley, et al. (2003). "Inorganic polyphosphate stimulates mammalian TOR, a kinase involved in the proliferation of mammary cancer cells." Proc Natl Acad Sci U S A 100(20): 11249-54.4. Zhang, H., K. Ishige, et al. (2002). "A polyphosphate kinase (PPK2) widely conserved in bacteria." Proc Natl Acad Sci U S A 99(26): 16678-83. |
Project Title: |
Evolution, validation and delivery of aptamer-based inhibitors that target the SARS coronavirus |
Investigator(s): |
Tanner JA |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
10/2005 |
Abstract: |
N/A |
Project Title: |
Evolution, validation and delivery of aptamer-based inhibitors that target the SARS coronavirus |
Investigator(s): |
Tanner JA, Miller A, Huang J, Kao RYT |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
10/2005 |
Abstract: |
Development of effective aptamer-based inhibitors of the SARs coronavirus. |
Project Title: |
Mechanistic Insight into Polyphosphate Kinase 2 - a Fundamental Enzyme of Polyphosphate Catabolism |
Investigator(s): |
Tanner JA |
Department: |
Biochemistry |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
04/2006 |
Abstract: |
Long polyphosphate chains were long thought to be irrelevant to biology and to be a by-product of metabolism, but recent discoveries have overhauled this view and have refocused attention on these fundamental simple molecules [1]. Polyphosphates act in prokaryotes as a control of growth, development, stress, an energy source, a buffer, a metal chelator, and play a role in RNA processing [2]. Perhaps even more significantly, in eukaryotes the molecules have been identified as being critical to certain proliferative signalling pathways of mammalian cells [3]. Two classes of enzymes have been discovered that synthesise these molecules from ATP – polyphosphate kinase 1 (PPK1) and polyphosphate kinase 2 (PPK2) [4]. Polyphosphates are simple and fundamental molecules, yet their roles remain poorly investigated, despite the possibility that structural and functional variation as introduced by branching could result in a completely new class of informational biological macromolecule. Last year, our team was awarded a grant from the Seed Funding for Basic Research scheme entitled “Comparative Characterisation of the Two Polyphosphate Kinases of M. tuberculosis”. The aim of that grant was to clone, purify and characterise PPK1 and PPK2 from Mycobacterium tuberculosis (MTB) with a view to drug development by inhibiting these enzymes (in a follow-up RGC grant application). Our initial hypothesis was that PPK1 was an ATP-driven and Mg2+-dependent polyphosphate kinase, whilst PPK2 was a GTP-driven and Mn2+-dependent polyphosphate kinase. Our research for that grant was successful in that we were able to test the hypothesis, but we actually found that PPK2 was far more effective in catalysing the reverse reaction of hydrolysing long-chain polyphosphate in the presence of GDP. This suggests a novel mechanism for forming energy rich nucleoside triphosphates (and possible tetraphosphates), and is a fascinating departure from our initial hypothesis. However, this opens up many fascinating questions but unfortunately meant that our research was premature for submission to the RGC in the 2005 round. With a view to submitting this research in the 2006 RGC round, here, our overall objective is to strengthen our hypothesis that PPK2 provides a novel route to nucleoside triphosphates from long-chain polyphosphates. We will achieve our objective in three stages: 1. Investigate whether GTP or Gp4 is generated during PPK2 mediated polyphosphate hydrolysis. At present, we use a gel-based assay that enables us to observe changes in polyphosphate chain length. It remains unclear whether phosphate or pyrophosphate is transferred to GDP, and hence whether GTP or Gp4 is generated during the reaction. This is essential mechanistic information prior to observing the details of the kinetics of PPK2 in stage 2. 2. Measure the precise kinetics of GTP/Gp4 formation and polyphosphate catabolism by PPK2 We will use various assays to examine the efficacy of GTP/Gp4 synthesis and the rates of polyphosphate catabolism, and compare these to published kinetic data for polyphosphate formation by PPK1. 3. Measure levels of polyphosphate in a cellular system comparing cells overexpressing PPK1 and PPK2. If our hypothesis holds true that PPK1 plays an anabolic role, whilst PPK2 plays a catabolic role, then we should expect that a system overexpressing PPK1 should have high polyphosphate levels, whilst a system overexpressing PPK2 should have low polyphosphate levels. It would be difficult for technical reasons to test this actually in MTB, but E. coli will act as an excellent model system for the function of the two enzymes. We will use cells overexpressing either MTB PPK1 or PPK2, and measure cellular polyphosphate levels under a variety of conditions. Stage 2 will provide enzymatic, and stage 3 will provide cellular evidence that support our revised hypothesis for PPK2 function. Besides being scientifically important with regards to our understanding of the roles of polyphosphate within the cell, these enzymes are excellent drug targets for development of new classes of MTB drugs. This will provide a firm foundation for a later submission to the RGC in 2006 to discover inhibitors of PPK2 for drug development against MTB. 1. Kornberg, A., N. N. Rao, et al. (1999). "Inorganic polyphosphate: a molecule of many functions." Annu Rev Biochem 68: 89-125. 2. Kuroda, A., K. Nomura, et al. (2001). "Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E. coli." Science 293(5530): 705-8. 3. Wang, L., C. D. Fraley, et al. (2003). "Inorganic polyphosphate stimulates mammalian TOR, a kinase involved in the proliferation of mammary cancer cells." Proc Natl Acad Sci U S A 100(20): 11249-54. 4. Zhang, H., K. Ishige, et al. (2002). "A polyphosphate kinase (PPK2) widely conserved in bacteria." Proc Natl Acad Sci U S A 99(26): 16678-83. |
List of Research Outputs |
Bernini A., Spiga O., Venditti V., Prischi F., Bracci L., Huang J., Tanner J.A. and Niccolai N., Tertiary structure prediction of SARS coronavirus helicase, Biochem Biophys Res Commun. 2006, 343: 1101-1104. |
Chan C.S.L., Chan D., Cheah K.S.E. and Tanner J.A., Purification and targeting sclerostin: Steps towards, osteoporosis therapy, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 2005. |
Choi M.Y., Chan D., Cheah K.S.E. and Tanner J.A., Functional studies on sedlin, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, 3 Dec . 2005. |
Choi M.Y., Chan C., Chan D., Luk K.D.K., Cheah K.S.E. and Tanner J.A., Mechanistic insight into point mutations in sedlin that result in spondyloepiphyseal dysplasia tarda, FASEB Journal. 2006, 873.9. |
Ge R., Watt R.M., Sun X., Tanner J.A., He Q., Huang J. and Sun H., Expression and characterization of a histidine-rich protein, Hpn: potential for Ni2+ storage in Helicobacter pylori, Biochemical Journal. 2006, 393: 285-293. |
Hughes S.J., Tanner J.A., Miller A.D. and Gould I.R., Molecular dynamics simulations of LysRS: an asymmetric state, Proteins. 2006, 62: 649-62. |
Peng Y., Yang P., Tanner J.A., Huang J., Li M., Lee H.H.F., Xu R.H., Kung H. and Lin M.C., Cold-inducible RNA binding protein is required for the expression of adhesion molecules and embryonic cell movement in Xenopus laevis, Biochem Biophys Res Commun. 2006, 344: 416-424. |
Tanner J.A., Wright M., Christie E.M., Preuss M.K. and Miller A.D., Investigation into the Interactions between Diadenosine 5',5'''-P1,P4-Tetraphosphate and Two Proteins: Molecular Chaperone GroEL and cAMP Receptor Protein, Biochemistry. 2006, 45: 3096-3106. |
Tanner
J.A., Mechanistic Insight into Point Mutations
in Sedlin that Result in Spondyloepiphyseal Dysplasia Tarda., International
Proteomics Symposium, |
Tanner
J.A., WTO TRIPS and its effect on the supply
and development of medicines in |
Zhang X., Chen B., Ng A.H.L., Tanner J.A., Tay D.K.C., So K.F., Rachel R.A., Copeland N.G., Jenkins N.A. and Huang J., Transgenic mice expressing cre-recombinase specifically in retinal rod bipolar neurons, Invest Ophthalmol Vis Sci. 2005, 46: 3515-20. |
Researcher
: Tong HK |
List of Research Outputs |
Tong
H.K., Ma
R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the
Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific
Community - Stem Cells, Senescence and Cancer. |
Tong
H.K., Ma
R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the
RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of
Medicine, HKU, |
Researcher
: Tsang ACC |
List of Research Outputs |
Tong
H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the
Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific
Community - Stem Cells, Senescence and Cancer. |
Tong
H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the
RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of
Medicine, HKU, |
List of Research Outputs |
Chan
D., Tsang K.Y., Cheslett
D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B.,
Yamada Y., Bateman J.F., Cheung K.M.C.
and Cheah K.S.E., Endoplasmic
reticulum stress and reprogramming of hypertrophic chondrocytes, Gordon
Research Conference: Collagen. |
Tsang
K.Y., Chan
D., Cheslett D., Chan W.C.W., So C.L., Kwan K.M., Hunziker E.B.,
Yamada Y., Bateman J.F., Cheung K.M.C.
and Cheah K.S.E., Chondroctes
Alleviate ER Stress Caused by Unfolded Proteins by Reprogramming, The
British Society for Matrix Biology. 25th Anniversary Meeting Pathobiology of
Bone and Cartilage. |
Tsang K.Y., Molecular pathogenesis of abnormal chondrocyte differentiation in a transgenic mouse model, PhD Thesis. 2006. |
Researcher
: Tsang SL |
List of Research Outputs |
Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005. |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Researcher
: Tsang SW |
List of Research Outputs |
Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022. |
Tsang
S.W. and Yao
K.M., Involvement of PDZD2 in The Regulation of Pancreatic Beta Cell
Development and Function , 10th Research Postgraduate Symposium, Faculty
of Medicine, HKU, |
Researcher
: Tsang SW |
List of Research Outputs |
Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022. |
Tsang
S.W. and Yao
K.M., Involvement of PDZD2 in The Regulation of Pancreatic Beta Cell
Development and Function , 10th Research Postgraduate Symposium, Faculty
of Medicine, HKU, |
Researcher
: Tsang WH |
List of Research Outputs |
Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. |
Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in Sox 10 mouse mutant, Mechanisms of Development. Elsevier, 2005, 122: S177. |
Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in a Sox10 mouse mutant generated by gene targeting , Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. |
Law
M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the
Enteric Neural Crest Development, 10th Research Postgraduate Symposium,
Faculty of Medicine, HKU, |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005. |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Researcher
: Tsang WH |
List of Research Outputs |
Chan K.T., Sae-Pang J.J., Kahmyer-Gabbe M., Tsang W.H., Tsang S.L. and Sham M.H., Disruption of the mouse Hoxb3 locus affects ventral body wall development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. |
Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in Sox 10 mouse mutant, Mechanisms of Development. Elsevier, 2005, 122: S177. |
Law M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., Abnormal enteric ganglia development in a Sox10 mouse mutant generated by gene targeting , Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. |
Law
M.L., Tsang W.H., Ngan E.S.W., Lui V.C.H. and Sham M.H., The Role of SOX10 in the
Enteric Neural Crest Development, 10th Research Postgraduate Symposium,
Faculty of Medicine, HKU, |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Analysis of multiple cardiac abnormalities of a mouse mutant Hoxb3lacZ, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September 2005. 2005. |
Sae-Pang J.J., Zhang J., Chan K.T., Tsang W.H., Tsang S.L. and Sham M.H., Investigation of Cardiovascular Defects in a Mouse Mutant HOXB3LACZ, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Researcher
: Wang J |
List of Research Outputs |
Wang J. and Huang J., Characterization of Intracellular Transportation in KbcU-Mutant Purkinje Cells., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005. |
Researcher
: Wang Y |
Project Title: |
The role of posttranslational modifications in regulating the oligomerization and biological functions of adiponectin |
Investigator(s): |
Wang Y, Xu A |
Department: |
Genome Research Centre |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
02/2005 |
Completion Date: |
06/2006 |
Abstract: |
The main objectives of this project are: 1) To investigate whether posttranslational modifications on each of the four lysine residues are required for the formation of the HMW species of adiponectin in mammalian cells; 2) To examine whether posttranslational modifications can modulate the secretion and/or intracellular assembly of the HMW form of adiponectin; 3) To use an adenovirus-mediated expression system to elucidate the roles of posttranslational modifications in regulating the anti-diabetic actions of adiponectin in vivo. |
Project Title: |
Proteomic and functional characterization of the plasma binding proteins fro the anti-diabetic and anti-inflammatory hormone adiponectin |
Investigator(s): |
Wang Y |
Department: |
Genome Research Centre |
Source(s) of Funding: |
Incentive Award for RGC CERG Fundable But Not Funded Projects |
Start Date: |
07/2005 |
Completion Date: |
06/2006 |
Abstract: |
N/A |
Project Title: |
The Fat-Derived Hormone Adiponectin as a Potential Factor Linking Obesity and Breast Cancer |
Investigator(s): |
Wang Y, Xu A |
Department: |
Genome Research Centre |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
06/2006 |
Abstract: |
1. Background and Research hypothesis: Obesity and its related diseases are now reaching an epidemic level and form one of the major burdens for our current healthcare system worldwide [1]. Recent epidemiological studies suggested that an increase in the risk of cancer is one of the consequences of obesity. The predominant cancers associated with obesity are lifestyle-related and have a hormonal base including breast, prostate, endometrium, colon and gallbladder cancers etc. [2]. Although the exact mechanism of this relationship remains to be determined, many evidence indicated that excess formation of adipose tissue surrounding the malignant cells might play important roles in tumor-microenvironment interaction and in controlling local cancer growth, invasion and distant metastasis [3]. Adipose tissue was traditionally considered to be an inert energy storage organ. However, recent evidences suggested that adipocytes (fat cells) can also produce a variety of biologically active polypeptides, hormones, growth factors and cytokines, collectively called adipokines [4]. Adipokines elicit their diversified actions on angiogenesis, inflammation, lipid/glucose metabolism, haemostasis, immunity and stress-response etc in an endocrine, paracrine and autocrine manner [5]. It is now generally accepted that endocrine dysfunction of adipose tissue may represent one of the causal links between obesity and systemic insulin resistance/diabetes. Interestingly, diabetes and hyperglycemia are also associated with an elevated risk of developing pancreatic, liver, colon, breast, and endometrial cancer [6], suggesting that the dysregulated secretion of adipokines might represent a general mechanism linking obesity and cancer formation. Indeed, many adipokines, such as leptin, tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6), not only causatively link to metabolic diseases but also play important roles in carcinogenesis. In addition, various growth factors/hormones produced from adipocytes in the local tumor environment might act directly on carcinoma cells to stimulate tumor growth and angiogenesis [7,8]. Breast cancer is the most frequent cancer in women and represents the second leading cause of cancer death among women [9]. Obesity is an independent risk factor for the development of breast cancer and is associated with late-stage disease and poor prognosis [10]. Post-menopausal women with upper body fat predominance have a higher risk of breast cancer [11]. The past several years have provided substantial evidence for the vital roles of stromal cells on the tumorigenesis of the mammary ductal epithelial cells [3]. Stromal cells can influence the level of invasiveness and malignancy of the tumor by producing various matrix metalloproteases (MMPs) and growth/angiogenesis stimulators including IGF, VEGF, HGF, FGF and TGF etc. Notably, adipocyte (fat cell) is one of the predominant stromal cell types in the microenvironment of mammary tissue and the proximity suggests that adipocytes could be a key player in the stromal-ductal epithelium interactions. Indeed, the close relationship between adipocytes and mammary tumor growth has been demonstrated by many in vitro and in vivo pharmacological studies [3]. Aromatase in adipose tissue stroma provides an important source of estrogen for the postmenopausal woman. Mature adipocytes can promote the growth of breast carcinoma cells in a collagen gel matrix culture through cancer-stromal cell interactions [12]. Co-transplantation of tumor cells with adipocytes into mice results in increased tumor growth and metastasis [13]. Leptin, a hormone mainly produced in adipose tissue, could act as a paracrine/endocrine growth factor towards mammary epithelial cells and contribute to the development of breast cancer [14,15]. A recent report by Iyengar P. et al suggested that collagen VI secreted from adipocytes could affect early mammary tumor progression and might represent one of the adipokines that have pro-tumorigenic functions [16]. In summary, these evidences suggest that adipose tissue-derived factors might significantly influence the growth and proliferation of tumorous stroma and malignant cells in the local environment of mammary tissue.Adiponectin is a circulating hormone exclusively secreted from adipocytes. Unlike many other adipokines, such as TNFα, IL-6, leptin, heparin-binding epidermal growth factor-like growth factor, hepatocyte growth factor and resistin etc that are increased in obesity, the circulating levels of adiponectin are inversely correlated with obesity and insulin resistance, two risk factors of breast cancer [10]. Adiponectin has been demonstrated to have insulin-sensitizing, anti-inflammatory, anti-diabetic and anti-atherogenic activities whereas most other adipokines are causatively linked to obesity-related diseases [17]. Replenishment of adiponectin in animal models can reduce the body weight, improve glucose/lipid homeostasis, increase insulin sensitivity, prevent atherosclerosis and ameliorate fatty liver diseases. In addition, adiponectin possesses anti-angiogenic and anti-tumor activities as demonstrated by its ability to inhibit cell growth and migration of vascular endothelial cells, prevent new blood vessel formation, and attenuate the growth of transplanted fibrosarcoma cell tumors in mice [18]. Although the detailed relationship between adiponectin expression in local mammary tissue and the development of breast cancer have not been fully established, recent clinical studies have shown that obese women have reduced serum adiponectin levels and low serum adiponectin levels are significantly associated with an increased risk for breast cancer [10,19-22]. Moreover, tumours in women with the low serum adiponectin levels are more likely to show a biologically aggressive phenotype [22]. Notably, we and others have shown that adiponectin has inhibitory activities on the proliferation of a variety of different types of cells, including aortic smooth muscle cells, myelomonocytic cells, endothelial cells and hepatic stellate cells etc [23-27]. It can selectively bind to various carcinogenic growth factor and prevent the interactions of these growth factors to their respective receptors [24]. In line with these clinical findings, our preliminary studies revealed that recombinant adiponectin could significantly attenuate the cell growth of an estrogen receptor (ER)-negative breast cancer cell line, MDA-MB-231, in a time-dependent manner. It could also inhibit the proliferation stimulated by insulin and several other growth factors in an ER-positive breast cancer cell line, T47D. Moreover, our results from DNA fragmentation assay suggest that apoptosis was significantly induced in MDA-MB-231 cells after 48 hours treatment with adiponectin. Based on aforementioned clinical and experimental evidences, we hypothesize that adiponectin might be a negative regulator in breast cancer development, and that replenishment of this protein might represent a novel therapeutic strategy for the treatment of obesity-related breast cancer. 2. Specific objectives:(1). To test whether adiponectin has inhibitory roles on the migration/invasion of breast carcinoma cells and the angiogenesis stimulated by these cells. (2). To investigate the potential mechanism that underlies the growth-inhibitory effects of adiponectin in breast cancer cells. (3). To evaluate the effects of adiponectin on tumor growth/metastasis in athymic nude mice inoculated with breast cancer cells using adenovirus-mediated overexpression system. |
List of Research Outputs |
Poppitt S.D., Leahy F.E., Keogh G.F., Wang Y., Mulvey T.B., Stojkovic M. and Cooper G.J., Effect of high-fat meals and fatty acid saturation on postprandial levels of the hormones ghrelin and leptin in healthy men. , Eur J Clin Nutr. 2006, 60: 77-84. |
Wang Y., Lam K.S.L., Chan L., Chan K.W., Lam J.B.B., Lam C.W., Hoo R.L.C., Mak W.W., Cooper G.J.S. and Xu A., Posttranslational modifications on the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high-molecular-weight oligomeric complex, J Biol Chem. 2006. |
Wang Y., Lam K.S.L., Cooper G.J. and Xu A., Structural and functional relationship of Adiponectin as an anti-aging hormone, Frontiers in Biomedical Research. 2005, 62. |
Xu A., Wang Y., Xu J., Stejskal D., Tam S., Zhang J., Wat N.M.S., Wong W.K. and Lam K.S.L., Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome, Clinical Chemistry. 2006, 52: 405-413. |
Researcher
: Wang Z |
List of Research Outputs |
Wang
Z. and Huang
J., Mechanism study on two DNA repair systems, 10th Research
Postgraduate Symposium, Faculty of Medicine, HKU, |
Researcher
: Watt RM |
Project Title: |
New Chemical Proteomics Methods For Selective Protein Capture And Identification |
Investigator(s): |
Watt RM, Che CM |
Department: |
Chemistry |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
09/2005 |
Abstract: |
Chemical proteomics (sometimes referred to as chemistry-based functional proteomics) is an extremely new and exciting area within the chemical biology field. It is broadly defined as being the integration of protein biochemistry and organic chemistry to study protein function on a genome wide scale. The main aims of chemical proteomics are to directly identify, quantify and characterize the ultimate products of genes, i.e. proteins: the bio-molecules that are the main effectors of activity within the cell. This is essential for a true and intimate understanding of cellular biology and function - one that cannot be gleamed solely from genetic or transcription-based analyses.Thus far, most of the research in chemical proteomics has centered on the design and synthesis of small chemical molecules that covalently label target proteins, enabling them to be subsequently identified and/or purified. These chemical probes are designed in such a way as to selectively modify certain classes of proteins, based upon mechanistic similarities (e.g. a shared active-site topography) or due to the nature or arrangement of their component amino acid residues. Aspects of this technology are related to two approaches commonly used in medicinal chemistry, for the identification of possible protein targets of drugs or other bio-molecules within the cell. In the first of these approaches, the drug (or an analogue of it) is linked to a resin or bead, which is used to capture interacting protein species from a cell-free extract. These are subsequently identified by mass spectrometry, protein sequencing or antibody-based methods. In the second approach, a radio- or fluorescently- labeled analogue of the drug or enzyme substrate is used to covalently modify the target protein, which is subsequently purified and identified.Thomas Kodadek (University of Texas Southwest Medical Center), Benjamin Cravatt (Scripps Institute, Skaggs Institute for Chemical Biology) and Matthew Bogyo (Celera Genomics and Stanford University) have conducted some innovative research in this field, developing a number of small chemical affinity probes to target classes of proteins that include proteases, hydrolases and phosphatases. They have outlined two main approaches: a) activity-based probes, and b) affinity-based probes. Activity-based chemical probes may be thought of as being analogous to mechanism-based or suicide inhibitors, in that they irreversibly label proteins directly as a result of their catalytic activities. Affinity-based probes may be thought of as being more general protein labeling agents, not directly linked to protein activity. These reagents do not necessarily target active sites residues, but still bind tightly to specific families of proteins, covalently modifying them. In addition, there are non-specific protein labeling reagents that chemically modify a broad range of proteins, usually targeting specific residues e.g. cysteine thiols or lysine amines.In this proposal, I will take a slightly different approach. I will synthesize a novel set of chemical affinity probes to target families of essential and ubiquitous metabolic and biosynthetic proteins/enzymes. The chemical affinity probes will contain a 'reactive' moiety that will be the main determinant for the types of proteins targeted, as well as a component that will enable subsequent affinity-based protein purification or localization on 2D gels by fluorimetry. Two main types of affinity probes will be synthesized: Highly selective probes targeting functionally-related protein families Less functionally-selective probes, targeting a broader range of proteinsStructurally simple reactive homologues of intermediates in common biosynthetic pathways will be used as components of the probes with a more general selectivity. The rationale behind this being that many of these intermediates are shared between different pathways (which are generally highly conserved between organisms), and they form the structural basis of numerous bioactive compounds. Choosing these types of compound maximizes the likelihood of finding chemical affinity probes of broad applicability. These chemical molecules will be designed to bind irreversibly to families of proteins within cells, in a cell or tissue extract (e.g. mouse liver extract, bacterial cell lysate, etc.) or in a biological fluid sample (e.g. plasma, plant sap, etc.).I will focus on (P450-type) oxidases; intermediates of fatty-acid and polyketide biosynthesis; amino acid and small-molecule biosynthesis and metabolism. Established mechanism-based enzyme inactivators will be used along with other simple drug and biosynthetic compound analogues. Synthetic strategies will be kept deliberately straightforward, maximizing the time spent on optimizing the protein labeling chemistry and experimental conditions, etc. I will consciously use compounds that will be relatively non-specific in nature to maximize the potential for serendipitous discovery. |
List of Research Outputs |
Yin W.X., Wu X.S., Li Z.H., Watt R.M., Huang J., Liu D.P. and Liang C.C., Targeted correction of a chromosomal point mutation by modified single-stranded oligonucleotides in a GFP recovery system, Biochemical and Biophysical Research Communications 334 (2005) 1032-1041. 2005. |
Researcher
: Wong CM |
List of Research Outputs |
Leung T.H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in Liver Cancer 2, DLC2, Suppresses Cell Transformation via Inhibition of Rhoa Activity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Researcher
: Wong EYM |
List of Research Outputs |
Wong E.Y.M., Chan Y.S., Wu D.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in mouse hindbrain causes abnormal ear development, 15th International Society of Developmental Biologist Congress 2005, Sydney Australia 3-7 September . 2005. |
Wong E.Y.M., Chan Y.S., Wu D.K. and Cheah K.S.E., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development., Mechanisms of Development . 2005, 122 (Supp 1): S88. |
Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia . 2005. |
Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Hoxb3 is involved in the endothelin-1 signaling pathway in patterning the facial branchial arches, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005. |
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. |
List of Research Outputs |
Lai
W.L. and Wong N.S.,
Regulation of GADD153 Expression at Post-transcriptional Level by ROS, 10th
Research Postgraduate Symposium, Faculty of Medicine, HKU, |
Wong N.S. and Poon W.H., The Kappa-opioid receptor specific agonist U50488H induces mitochondrial stress in cultured human cancer cells., The FEBS Journal (formerly European Journal of Biochemistry). 2005, 272, Supplement 1: n5-029p. |
Researcher
: Wong PM |
List of Research Outputs |
Wong P.M., Lu L. and Sham M.H., HOXB3 Mutation Generated By Gene Targeting Leads to Plasmacytoma, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Researcher
: Wong SYY |
List of Research Outputs |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006. |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25. |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, 15th International Society of Developmental Biologists Congress 2005, Sydney, Australia, 3-7 September . 2005. |
Researcher
: Wynn SL |
List of Research Outputs |
Au Y.K., Wynn S.L., Cheung K.M.C. and Cheah K.S.E., Foxa2 minimal notochord enhancer element mediates Cre expression in the node and notochord, Mechanisms of Development. 2005, 122 (Supp 1): S88. |
Au Y.K., Wynn S.L., Cheung K.M.C. and Cheah K.S.E., Foxa2 minimal notochord enhancer element mediates Cre expression in the node and notochord, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia. 2005. |
Project Title: |
Investigating the functional involvement of PDZD2 in the regulation of pancreatic beta cell gene expression and function |
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: |
Investigating the functional involvement of PDZD2 in the regulation of pancreatic beta cell gene expression and function |
Investigator(s): |
|
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
01/2005 |
Abstract: |
N/A |
Project Title: |
Activation of FOXM1 by the Raf/MEK/MAK pathway and regulation of cell cycle progression at the G2/M phase |
Investigator(s): |
|
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
09/2005 |
Abstract: |
N/A |
Project Title: |
Activation of FOXM1 by the Raf/MEK/MAK pathway and regulation of cell cycle progression at the G2/M phase |
Investigator(s): |
|
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 E2A proteins that regulate the gene expression
and physiological function of diverse cell types including pancreatic beta
cells (1). Recent analysis of PDZD2 expression reveals strong expression of
the protein in pancreatic insulin-secreting beta cells, but not the
glucagon-secreting alpha cells. (2) Using an antiserum raised against the
C-terminus of the PDZD2, we demonstrated that full-length PDZD2 is subjected
to extensive proteolytic processing to generate its C-terminus as a ~37kDa
secreted protein, named sPDZD2 (3). Immunoblot analysis indicated expression
of both the full-length and secreted forms of PDZD2 in the beta-like cell
line INS-1E (2). INS-1E cells express many of the properties of isolated
primary rat islet beta cells, including glucose-stimulated insulin secretion,
and represent a ready source of beta-like cells for functional and gene
expression analysis. To investigate the extracellular signaling function of
sPDZD2, a recombinant sPDZD2 protein was synthesized. In culture media with
limiting serum, co-incubation with sPDZD2 stimulated the proliferation of
INS-1E cells (2). The mitogenic effect was concentration-dependent, with
maximal effects detected at concentrations ranging from 0.001 nM to 0.1 nM.
As a mitogen of beta-like cells, sPDZD2 will be useful for the optimization
of beta cell growth and differentiation in vitro. Little is known about the
molecular mechanism(s) underlying the mitogenic effect of sPDZD2.
Interestingly, pancreatic islet cells, isolated from a transgenic mouse line
with sPDZD2 over-expressed using the rat insulin II promoter, showed dramatic
decreases in insulin secretion upon glucose stimulation (4). In islet beta
cells, the glucose-sensitive secretory response is triggered by suppression
of the ATP-sensitive potassium (KATP) channels (5). At low plasma glucose
concentrations, KATP channels remain open to maintain the hyperpolarized (or
background) state. With increases in glucose level and hence the ATP/ADP
ratio, KATP channels become inhibited and the resulting membrane
depolarization leads to activation of calcium channels and eventually insulin
release. Also involved in the regulation of action potential in
insulin-secreting cells are the delayed outward rectifier Kv channels, which
express at high levels in pancreatic beta cells (6). It would be very
interesting to determine whether sPDZD2 exerts its inhibitory effect on
glucose-stimulated insulin secretion through modulation of KATP and Kv
channel activities. Further, a functional link between cell proliferation and
Kv channel activity has been demonstrated recently. It remains to be analyzed
whether modulation of Kv channel activity may be a means by which sPDZD2
exercises its concentration-dependent mitogenic effects on INS-1E cells. Two
recent communications also indicate a connection between PDZD2/sPDZD2 and ion
channel function. Using yeast two-hybrid screens, Dr. Stockand (University of
Texas Health Science Center) and Dr. Okuse (Imperial College London)
independently identified PDZD2 as the interactor of sodium channels (ENaC and
Nav1.8, respectively). For ENaC, co-expression with a GFP-fusion protein containing
just the last two PDZ domains as in sPDZD2 was enough to activate channel
activity by 8-fold. On the other hand, suppression of PDZD2 expression in
cultured sensory neurons by siRNA caused a huge reduction of Nav1.8 current.
Taken together, these preliminary findings point towards PDZD2/sPDZD2 playing
novel regulatory roles on channel function. We hypothesize that sPDZD2 exerts
its effect on the proliferation and secretory function of INS-1E cells via
modulation of potassium channel activities. In collaboration with Dr. G. Li
(Department of Medicine, HKU), we propose to investigate the effect of
recombinant sPDZD2 on the activities of KATP and Kv channels expressed in
INS-1E cells. Any detectable effect will be correlated with the mitogenic and
secretory responses of the treated cells. The proposed analyses will shed
light into the molecular mechanism underlying the biological effects of
sPDZD2, which is of major biological interest and relevance to devising
better strategies to enhance beta cell growth for islet transplantation.
Reference 1. Thomas, M. K.+, |
List of Research Outputs |
Lee J.H., Volinic J.L., Banz C., Yao K.M. and Thomas M.K., Interactions with p300 enhance transcriptional activation by the PDZ-domain coactivator Bridge-1., J. Endocrinol. 2005, 187: 283-292. |
Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005. |
Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022. |
Madureira P.A., Varshochi R., Constantinidou D., Francis R.E., Coombes R.C., Yao K.M. and Lam E.W., The Forkhead box M1 protein regulates the transcription of the estrogen receptor alpha in breast cancer cells., J. Biol. Chem.. 2006, 281: 25167-25176. |
Tam C.W., Cheng A.S., Lam A.C.W., Yik S.Y., Yao K.M. and Shiu S.Y.W., Prostate Cancer Growth Modulation By sPDZD2, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005, 1.18. |
Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung G.W.Y. and Yao K.M., Regulation of FOXM1c by the Raf/MEK/MAPK pathway, Keystone Symposia, Connecting the Scientific Community - Stem Cells, Senescence and Cancer. Singapore, Oct 25 - Oct 30, 2005. |
Tong H.K., Ma R.Y.M., Cheung M.S., Tsang A.C.C., Leung W.L. and Yao K.M., Regulation of Foxmic By the RAF/MEK/MAPK Pathway, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005. |
Tsang S.W. and Yao K.M., Involvement of PDZD2 in The Regulation of Pancreatic Beta Cell Development and Function , 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Researcher
: Yau TO |
Project Title: |
The role of HDPR1, a novel inhibitor of the WNT/β-catenin signalling pathway, in hepatocellular carcinoma |
Investigator(s): |
Yau TO, |
Department: |
Centre for the Study of Liver Disease |
Source(s) of Funding: |
Small Project Funding |
Start Date: |
11/2004 |
Completion Date: |
10/2005 |
Abstract: |
To study the expression of HDPR1 at mRNA levels in human HCCs and HCC cell lines; to investigate the common mechanisms, such as promoter hypermethylation and loss of heterozygosity, by which the expression of HDPR1 in HCC is downregulated; to study the function of HDPR1 in HCC cell lines. |
List of Research Outputs |
Researcher
: Yeung ML |
List of Research Outputs |
Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005. |
Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022. |
Researcher
: Yeung ML |
List of Research Outputs |
Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005. |
Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022. |
List of Research Outputs |
Yeung
M.N., Zhou
Z., Chan D. and Shum D.K.Y., Expression of heparanase in
newborn mouse growth plates, Glycoconjugate Journal, GlycoXVIII, XVIII
International Symposium on Glycoconjugates, |
Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan Sulfates and Heparanase in the Mineralizing Matrix of Developing Mouse Growth Plate., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Yeung
M.N., Zhou
Z., Chan D. and Shum D.K.Y., Heparan sulfates and
heparanase at the mineralization front of the developing growth plate., Proteoglycans
in Signaling, |
Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57. |
Researcher
: Yip MS |
List of Research Outputs |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Yip M.S., Leung K.K.H., Dung W.F., Chan D., Shang C., Prall O., Mohun T.J., Harvey R.P. and Tam P.P.L., Procollagen IIA facilitates BMP signaling in heart development, Hugo, HGM2006, 31 May - 3 June 2006 Helsinki, Finland . 2006. |
Researcher
: Zhang JCL |
Project Title: |
Functional analysis of SM22[beta] by tissue-specific targeted deletion in mice |
Investigator(s): |
Zhang JCL, Cheah KSE, Lau CP, Feil R., Parmacek M.S. |
Department: |
Medicine |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
09/2003 |
Completion Date: |
09/2005 |
Abstract: |
N/A |
Project Title: |
Cardiovascular analysis of a novel murine model of cardiomyopathy and sudden death |
Investigator(s): |
Zhang JCL |
Department: |
Medicine |
Source(s) of Funding: |
Incentive Award for RGC CERG Fundable But Not Funded Projects |
Start Date: |
07/2004 |
Completion Date: |
09/2005 |
Abstract: |
N/A |
List of Research Outputs |
Cheah
K.S.E. and Zhang J.C.L.,
Procollagen IIA deficient mice. , |
Cheah K.S.E., Wong S.Y.Y., Zhang J.C.L., Leung W.L., Chan D. and Tam P.P.L., Procollagen IIA regulates BMP/TGFb signaling in patterning the heart and its major vessels, Mechanisms of Development. 2005, 122(Supp 1): S25. |
Researcher
: Zhang X |
List of Research Outputs |
Zhang X., Chen B., Ng A.H.L., Tanner J.A., Tay D.K.C., So K.F., Rachel R.A., Copeland N.G., Jenkins N.A. and Huang J., Transgenic mice expressing cre-recombinase specifically in retinal rod bipolar neurons, Invest Ophthalmol Vis Sci. 2005, 46: 3515-20. |
Researcher
: Zhang Y |
List of Research Outputs |
Zhang
Y. and Shum
D.K.Y., Functional Study of Heparanase in the explant cultures of rat
dorsal root ganglia., 10th Research Postgraduate Symposium, Faculty of
Medicine, HKU, |
Zhang Y., Yeung M.N., Liu J., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats. , J Comp Neurol.. 2006, 494(2): 345-57. |
Researcher
: Zhou Z |
Project Title: |
Investigation of alternations in growth factor signaling and their contribution to defective intramembranous bone formation in mice lacking MT1-MMP |
Investigator(s): |
Zhou Z |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
09/2003 |
Abstract: |
To understand the Nature of defective calvarial osteogenesis and alterations in FGF signaling in MT1-MMP homozygous mutant mice; to regulate the MT1-MMP by FGF signaling. |
Project Title: |
Investigation of alternations in growth factor signaling and their contribution to defective intramembranous bone formation in mice lacking MT1-MMP |
Investigator(s): |
Zhou Z |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
09/2003 |
Abstract: |
N/A |
Project Title: |
Investigating the mechanism underlying anti-cancer effect of farnesyl transferase inhibitors |
Investigator(s): |
Zhou Z |
Department: |
Biochemistry |
Source(s) of Funding: |
Seed Funding Programme for Basic Research |
Start Date: |
01/2005 |
Completion Date: |
12/2005 |
Abstract: |
In this study, we will assess whether FT inhibitors cause growth arrest in tumor cells by compromise the DNA repair machinery. We will also make two constructs that express mutant prelamin A or lamin A to assess whether expressing truncated or unprocessed lamin A in tumor cells will cause increased genomic instability and enhanced sensitivity to chemotherapy. This study will help to understand the profound effects of FT inhibitors on tumor cells and help to develop effective chemotherapy in cancer patients. |
Project Title: |
Genomic instability and premature aging in mice lacking Zmpste24 |
Investigator(s): |
Zhou Z |
Department: |
Biochemistry |
Source(s) of Funding: |
Merit Award for RGC CERG Funded Projects |
Start Date: |
08/2005 |
Abstract: |
N/A |
Project Title: |
Genomic instability and premature aging in mice lacking Zmpste24 |
Investigator(s): |
Zhou Z, Cheah KSE |
Department: |
Biochemistry |
Source(s) of Funding: |
Competitive Earmarked Research Grants (CERG) |
Start Date: |
08/2005 |
Abstract: |
To examine genomic stability in Zmpste24-I- mice and in human fibroblasts derived from HGPS patients; to assess whether unprocessed prelamin A is a causing factor for unstable genome and premature aging; to assess the impact of Zmpste24 deficiency and mutated lamin A on DNA repair; to assess whether loss of Zmpste24 and mutated lamin A results in mis-localized and decreased pRB protein. |
Project Title: |
Understanding the regulation of MT1-MMP activity in tumorigenesis |
Investigator(s): |
Zhou Z |
Department: |
Biochemistry |
Source(s) of Funding: |
Matching Fund for NSFC Young Researcher Award |
Start Date: |
05/2006 |
Abstract: |
To investigate the effect of mis-regulated MT1-MMP activity on development and tumorigenesis; to understand how the mis-regulated MT1-MMP activity regulate FGF signaling which contributes to the defective development and disturbed angiogenesis. |
List of Research Outputs |
Björndahl M., Cao R., Nissen J., Clasper S., Xie Y., Zhou Z., Jackson D., Jon Hansen A. and Cao Y., Insulin-like Growth Factor-1and -2 Induce Lymphangiogenesis , Proc Natl Acad Sci Usa. 2005, 102(43): 15593-8. |
Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785. |
Religa P., Cao R., Bjorndahl M., Zhou Z., Zhu Z. and Cao Y., Presence Of Bone Marrow-derived Circulating Progenitor Endothelial Cells In The Newly Formed Lymphatic Vessels, Blood. 2005, 106(13): 4184-90. |
Wang J., Hoshijima M., Lam J., Zhou Z., Jokiel A., Dalton N.D., Hultenby K., Ruiz-Lozano P., Ross J., Tryggvason K. and Chien K.R., Cardiomyopathy Associated With Microcirculation Dysfunction In Laminin Alpha4 Chain-deficient Mice, J Biol Chem. 2006, 281(1): 213-20. |
Yeung
M.N., Zhou Z., Chan D. and Shum D.K.Y., Expression of heparanase in
newborn mouse growth plates, Glycoconjugate Journal, GlycoXVIII, XVIII
International Symposium on Glycoconjugates, |
Yeung M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan Sulfates and Heparanase in the Mineralizing Matrix of Developing Mouse Growth Plate., 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
Yeung
M.N., Zhou Z., Chan D. and Shum D.K.Y., Heparan sulfates and heparanase
at the mineralization front of the developing growth plate., Proteoglycans
in Signaling, |
Zhou
Z., Distinguished Oversea Young Scientist
Award, National Natural Science Foundation of |
Zhou Z., Genomic Instability in Laminopathies the difference between Cardiomyopathy and muscular dystrophy, Harvard University. 2005. |
Zhou Z., Genomic Instability in Laminopathy-based Premature Aging, Annual Meeting of American Society of Cell Biology. 2005. |
Zhou
Z., How To Get Old Fast? , Karolinska
Institute, |
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