GENOME RESEARCH CENTRE
| Researcher : Fong PY |
| List of Research Outputs |
| Fong P.Y., Xue W., Ngan H.Y.S., Chiu P.M., Chan Y.K., Tsao G.S.W. and Cheung A.N.Y., Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study, Journal of Clinical Pathology. 2006, 59: 179-183. |
| Researcher : Leung TY |
| List of Research Outputs |
| Wang Y., Lam K.S.L., Leung T.Y. and Xu A., Overexpression of Angiopoietin-like Protein 4 Alters the Protein Expression Profiles of the Liver Tissue in DB/DB Diabetic Mice, Molecular & Cellular Proteomics. HUPO 4th Annual Congress, 2005, 4 (S1): S200. |
| Researcher : Mak WW |
| List of Research Outputs |
| Chan V.S.F., Chan Y.K., Chen Y., Poon L.L.M., Cheung A.N.Y., Zheng B., Chan K.H., Mak W.W., Ngan H.Y.S., Xu X., Screaton G., Tam P.K.H., Austyn J.M., Chan L.C., Yip S.P., Peiris J.S.M., Khoo U.S. and Lin C.L., Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection. , Nature Genetics. 2006, 38: 38-46. |
| 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. |
| Tai L.S., Mak W.W., Ng P.K.M., Chua D.T.T., Fu L., Chu K.W., Song Y. and Chen M., High-throughput Loss-of-Heterozygosity Study of Chromosome 3p in Lung Cancer Using Single-Nucleotide Polymorphism Markers, In: Tai AL, Mak W, Ng PK, Chua DT, Ng MY, Fu L, Chu KK, Fang Y, Qiang Song Y, Chen M, Zhang M, Sham PC, Guan X , Cancer Research. 2006, 66(8): 4133-4138. |
| The International HapMap Consortium &., Tsui L.C., Mak W.W., Sham P.C., Song Y. and Tam P.K.H., A haplotype map of the human genome. The International HapMap Consortium (Co-PI of Hong Kong Centre which responsible 2.5% of genome), Nature. 2005, 437: 1299-1319. |
| The International HapMap Consortium H.K.U., Tsui L.C., Mak W.W., Sham P.C., Song Y. and Tam P.K.H., A haplotype map of the human genome (Co-PI of Hong Kong Centre which responsible for 2.5% of genome), Nature. 2005, 437: 1299-1320. |
| 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. and Xu A., Post-translational modifications of 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, 281: 16391-400. |
| 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. |
| Researcher : Ng PKM |
| 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. |
| Tai L.S., Mak W.W., Ng P.K.M., Chua D.T.T., Fu L., Chu K.W., Song Y. and Chen M., High-throughput Loss-of-Heterozygosity Study of Chromosome 3p in Lung Cancer Using Single-Nucleotide Polymorphism Markers, In: Tai AL, Mak W, Ng PK, Chua DT, Ng MY, Fu L, Chu KK, Fang Y, Qiang Song Y, Chen M, Zhang M, Sham PC, Guan X , Cancer Research. 2006, 66(8): 4133-4138. |
| Researcher : So MT |
| List of Research Outputs |
| Garcia-Barcelo M.M., So M.T., Lau K.C., Leon Y.Y., Yuan Z., Cai W., Lui V.C.H., Fu M., Herbrick J.A., Gutter E., Proud V., Li L., Pierre-Louis J., Aleck K., van Heurn E., Belloni E., Scherer S.W. and Tam P.K.H., Population differences in the polyalanine domain and 6 new mutations in HLXB9 in patients with Currarino syndrome, Clinical Chemistry. 2006, 52(1): 46-52. |
| Researcher : Song Y |
| Project Title: | Genetic linkage analysis of early onset degenerative disc disease in Southern Chinese |
| Investigator(s): | Song Y, Cheah KSE, Cheung KMC, Leong JCY, Chan D |
| Department: | Biochemistry |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 11/2003 |
| Abstract: |
| To detect linkage associated with early onset familial DDD by performing a genome-wide scan; to define the chromosomal location of the early onset familial DDD gene; to begin preliminary work towards positional/candidate clonning. |
| Project Title: | Genetic linkage analysis of early onset degenerative disc disease in Southern Chinese |
| Investigator(s): | Song Y, Cheah KSE, Cheung KMC, Leong JCY, Chan D |
| Department: | Biochemistry |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 11/2003 |
| Abstract: |
| N/A |
| Project Title: | Genetic study of Alzheimer disease in Chinese |
| Investigator(s): | Song Y, Sham PC, Chu LW |
| Department: | Genome Research Centre |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 01/2005 |
| Completion Date: | 06/2006 |
| Abstract: |
| The main objectives of the project are: 1) To establish the methodology for genome-wide association analysis using pooled DNA samples and the Affymetrix 100k GeneChip at the Genome Research Centre, so that this can be provided as a service to investigators. 2) To detect novel susceptibility loci for Alzheimer's disease using this methodology. |
| Project Title: | Mapping and cloning a new gene on chromosome 8q24 for amyotrophic lateral sclerosis in a large Chinese family |
| Investigator(s): | Song Y |
| Department: | Biochemistry |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2005 |
| Abstract: |
| N/A |
| Project Title: | Mapping and cloning a new gene on chromosome 8q24 for amyotrophic lateral sclerosis in a large Chinese family |
| Investigator(s): | Song Y, Ho SL, Fong CY, Ramsden D.B. |
| Department: | Biochemistry |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 01/2005 |
| Abstract: |
| Biomarkers detection; detection possible ALS modifier on chromosome 10 in Branch A; longitudinal follow-up of both branches; mapping the CMT II locus in Branch B. |
| Project Title: | Mapping a genetic modifier for heart defects in Type IIA procollagen deficient mutant mice |
| Investigator(s): | Song Y |
| Department: | Genome Research Centre |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2006 |
| Abstract: |
| N/A |
| Project Title: | Mapping a genetic modifier for heart defects in Type IIA procollagen deficient mutant mice |
| Investigator(s): | Song Y, Cheah KSE, Sham PC |
| Department: | Genome Research Centre |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 01/2006 |
| Abstract: |
| To perform a genome-wide scan using mouse microsatellite markers to map the modifer locus to within a 20cM region; to generate region-specific speed modifer congenic mice for fine mapping of this 20cM region; to map the modifier locus to a 1cM region and combine with the results of gene expression in the modifier region to provide the essential genetic resources for future studies aimed at precise identification of the modifier gene. |
| List of Research Outputs |
| Tai L.S., Mak W.W., Ng P.K.M., Chua D.T.T., Fu L., Chu K.W., Song Y. and Chen M., High-throughput Loss-of-Heterozygosity Study of Chromosome 3p in Lung Cancer Using Single-Nucleotide Polymorphism Markers, In: Tai AL, Mak W, Ng PK, Chua DT, Ng MY, Fu L, Chu KK, Fang Y, Qiang Song Y, Chen M, Zhang M, Sham PC, Guan X , Cancer Research. 2006, 66(8): 4133-4138. |
| The International HapMap Consortium &., Tsui L.C., Mak W.W., Sham P.C., Song Y. and Tam P.K.H., A haplotype map of the human genome. The International HapMap Consortium (Co-PI of Hong Kong Centre which responsible 2.5% of genome), Nature. 2005, 437: 1299-1319. |
| The International HapMap Consortium H.K.U., Tsui L.C., Mak W.W., Sham P.C., Song Y. and Tam P.K.H., A haplotype map of the human genome (Co-PI of Hong Kong Centre which responsible for 2.5% of genome), Nature. 2005, 437: 1299-1320. |
| 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 |
| Chen B., Lam K.S.L., Wang Y., Wu D., Lam C.W., Shen J., Wong L.C., Hoo R.L.C., Zhang J. and Xu A., Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes, Biochem Biophys Res Commun. 2006, 341: 549-56. |
| Fang X., Pananivel R., Zhou X., Liu Y., Xu A., Wang Y. and Sweeney G., Hyperglycemia- And Hyperinsulinemia-induced Alteration Of Adiponectin Receptor Expression And Adiponectin Effects In L6 Myoblasts. , J Mol Endocrinol. Society for Endocrinology, 2005, 35: 465-76. |
| Poppitt S.D., Leahy F.E., Keogh G.F., Wang Y., Mulvey T.B., Stojkovic M., Chan Y.K., Choong Y.S., McArdle B.H. and Cooper G.J.S., Effect of High-fat Meals and Fatty Acid Saturation on Postprandial Levels of the Hormones Ghrelin and Leptin in Healthy Men, European Journal of Clinical Nutrition. 2005. |
| Wang Y., Lam K.S.L., Leung T.Y. and Xu A., Overexpression of Angiopoietin-like Protein 4 Alters the Protein Expression Profiles of the Liver Tissue in DB/DB Diabetic Mice, Molecular & Cellular Proteomics. HUPO 4th Annual Congress, 2005, 4 (S1): S200. |
| Wang Y., Lam K.S.L., Lam M. and Xu A., Overexpression of Angiopoietin-like protein 4 alters the protein expression profiles of the liver tissue in db/db diabetic mice, HUPO 4th Annual World Congress. 2005, 4: S200. |
| 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. and Xu A., Post-translational modifications of 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, 281: 16391-400. |
| Researcher : Xu R |
| Project Title: | Oral gene therapy of tumors by using recombinant AAV-TRAIL viral vectors |
| Investigator(s): | Xu R, Kung H |
| Department: | Institute of Molecular Biology |
| Source(s) of Funding: | Matching Fund for Hi-Tech Research and Development Program of China (863 Projects) |
| Start Date: | 05/2002 |
| Abstract: |
| To study tumor therapy by using recombinant AAV. |
| Project Title: | Peroral transduction of hepatocytes for diabetes gene therapy |
| Investigator(s): | Xu R, Lam KSL |
| Department: | Institute of Molecular Biology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 10/2002 |
| Abstract: |
| A major goal of gene therapy for Diabetes Mellitus (DM) is to restore long-term euglycemia. This study shall focus on clarifying the adeno-associated virus (AAV) vector transportation pathway from stomach to liver after oral administration. The research team will extend their previous study further to develop chimeric glucose- and insulin-sensitive promoters and insert them into the existing AAV vector system. |
| Project Title: | Preclinical study of lung cancer therapy using recombinant adeno-associate virus vector |
| Investigator(s): | Xu R |
| Department: | Institute of Molecular Biology |
| Source(s) of Funding: | Matching Fund for Hi-Tech Research and Development Program of China (863 Projects) |
| Start Date: | 04/2003 |
| Abstract: |
| To carrry out preclinical study of lung cancer therapy using recombinant adeno-associate virus vector. |
| List of Research Outputs |
| Xu R., Ma H., Li H., Sham M.H., Li E.T.S., Tam P.K.H. and Lam K.S.L., Oral viral vector gene delivery, In: Redberry GW (ed). Trends in Gene Therapy Research. New York, U.S.A., Nova Sciecen Publishers, Inc., 2005, 191-221. |