GENOME RESEARCH CENTRE

Researcher : Fong PY

List of Research Outputs

 

Fong P.Y., Garcia-Barcelo M.M., Sham P.C., Ng P.K.M., Lau C.F., So M.T., Mak W.W. and Tam P.K.H., Genetic mapping for RET-dependent modifiers in Hirschsprung disease (HSCR), 56th Annual Meeting of the American Society of Human Genetics, New Orleans, U.S.A., 9-13 October 2006.

 

Researcher : Lau CF

List of Research Outputs

 

Fong P.Y., Garcia-Barcelo M.M., Sham P.C., Ng P.K.M., Lau C.F., So M.T., Mak W.W. and Tam P.K.H., Genetic mapping for RET-dependent modifiers in Hirschsprung disease (HSCR), 56th Annual Meeting of the American Society of Human Genetics, New Orleans, U.S.A., 9-13 October 2006.

 

Researcher : Leung TY

List of Research Outputs

 

Leung T.Y., Wang Y., Ng W.C. and Leung K.M.Y., Characterisation of metallothioneins in the green-lipped mussel Perna viridis induced by metal and non-metal stressors using proteomics, Society of Environmental Toxicology and Chemistry (SETAC) Asia/Pacific 2006 meeting, 18-20 September, 2006, Peking University, Beijing, China. 2006.

 

Leung T.Y., Wang Y., Ng W.C. and Leung K.M.Y., Proteomic characterization of biomarkers in a common marine biomonitor Perna viridis exposed to waterborne cadmium and hydrogen peroxide, The 5th international Conference on Marine Pollution and Ecotoxicology, 3-6 June 2007, City University of Hong Kong, Hong Kong. 2007.

 

Researcher : Mak WW

List of Research Outputs

 

Chik S.C.C., Lee D.C.W., Li C.B., Mak W.W., Tam P.K. and Lau A.S.Y., Immunomodulatory Effects of Ginseng on Human Monocytic Cells, The 6th International Symposium on Natural Medicine and Microflora (6th ISNMM), Seoul, Korea, 6-8 August 2006. 100-101.

 

Fong P.Y., Garcia-Barcelo M.M., Sham P.C., Ng P.K.M., Lau C.F., So M.T., Mak W.W. and Tam P.K.H., Genetic mapping for RET-dependent modifiers in Hirschsprung disease (HSCR), 56th Annual Meeting of the American Society of Human Genetics, New Orleans, U.S.A., 9-13 October 2006.

 

Kong K.P., Chong W.P., Wong W.H.S., Lau W.C.S., Chan T.M., Ng P.K.M., Song Y., Mak W.W. and Lau Y.L., p21 gene polymorphisms in systemic lupus erythematosus, Rheumatology. Oxford University Press, 2006, doi:10.1093/rheumatology/kel210: 1-7.

 

Researcher : Ng DCM

List of Research Outputs

 

Shih C.H., Siu S.O., Wong E., Chiu L.C.M., Ng D.C.M., Chu I.K. and Lo C.S.C., Quantitative analysis of anticancer 3-deoxyanthocyanidins in infected sorghum seedlings, Journal of Agricultural and Food Chemistry. 2007, 55: 254-259.

 

Researcher : Ng PKM

List of Research Outputs

 

Fong P.Y., Garcia-Barcelo M.M., Sham P.C., Ng P.K.M., Lau C.F., So M.T., Mak W.W. and Tam P.K.H., Genetic mapping for RET-dependent modifiers in Hirschsprung disease (HSCR), 56th Annual Meeting of the American Society of Human Genetics, New Orleans, U.S.A., 9-13 October 2006.

 

Kong E.K.P., Chong W.P., Wong W.H.S., Chan D.T.M., Ng P.K.M., Song Y., Mak W. and Lau Y.L., p21 Gene Polymorphisms in Systemic Lupus Erythematosus, Rheumatology (Oxford, England). England, Oxford University Press, 2007, 46(2): 220-226.

 

Kong K.P., Chong W.P., Wong W.H.S., Lau W.C.S., Chan T.M., Ng P.K.M., Song Y., Mak W.W. and Lau Y.L., p21 gene polymorphisms in systemic lupus erythematosus, Rheumatology. Oxford University Press, 2006, doi:10.1093/rheumatology/kel210: 1-7.

 

Researcher : Song Y

Project Title:

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

Investigator(s):

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

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

11/2003

 

Abstract:

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

 

Project Title:

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

Investigator(s):

Song Y, Ho SL, Fong CY

Department:

Biochemistry

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2005

 

Abstract:

Biomarkers detection; detection possible ALS modifier on chromosome 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, 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

 

Cheung K.M.C., Luk K.D.K., Ho D.W.H., Chan D., Cheah K.S.E. and Song Y., Linkage analysis on familial early-onset degenerative disc disease. , Best Poster Award. 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong. 2007.

 

Cheung K.M.C., Song Y., Kao P.Y.P., Ho D.W.H., Fan B., Karppinen J., Yip S.P., Leong J.C.Y., Luk K.D.K., Ott J., Cheah K.S.E., Sham P.C. and Chan D., Three genes in the aggrecan degraduation pathway act synergistically to predispose to degenerative disc disease, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 2007.

 

Ho D.W.H., Cheung K.M.C., Chan D., Karppinen J., Yip S.P., Ott J., Luk K.D.K., Leong J.C.Y., Cheah K.S.E., Sham P.C. and Song Y., Linkage analysis on familial early onset degenerative disc disease, 34th Annual Meeting of International Society for the Study of the Lumbar Spine, Hong Kong, June 10-14, 2007.

 

Kong E.K.P., Chong W.P., Wong W.H.S., Chan D.T.M., Ng P.K.M., Song Y., Mak W. and Lau Y.L., p21 Gene Polymorphisms in Systemic Lupus Erythematosus, Rheumatology (Oxford, England). England, Oxford University Press, 2007, 46(2): 220-226.

 

Kong K.P., Chong W.P., Wong W.H.S., Lau W.C.S., Chan T.M., Ng P.K.M., Song Y., Mak W.W. and Lau Y.L., p21 gene polymorphisms in systemic lupus erythematosus, Rheumatology. Oxford University Press, 2006, doi:10.1093/rheumatology/kel210: 1-7.

 

Researcher : Wang Y

Project Title:

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

Investigator(s):

Wang Y, Xu A

Department:

Genome Research Centre

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

06/2006

 

Abstract:

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

 

List of Research Outputs

 

Cheng K.Y., Lam K.S.L., Wang Y. and Xu A., Adiponectin as a key player of inflammation, In: Fantuzzi G, Biomedical Reviews. 2006, 17: 11-22.

 

Cheng K.Y., Lam K.S.L., Wang Y., Yu H., Carling D., Wu D., Wong C.W. and Xu A., Adiponectin-induced eNOS activation and Nitric Oxide Production are Mediated by APPL1 in Endothelial Cells, Diabetes. 2007, 56: 1387-94.

 

Leung T.Y., Wang Y., Ng W.C. and Leung K.M.Y., Characterisation of metallothioneins in the green-lipped mussel Perna viridis induced by metal and non-metal stressors using proteomics, Society of Environmental Toxicology and Chemistry (SETAC) Asia/Pacific 2006 meeting, 18-20 September, 2006, Peking University, Beijing, China. 2006.

 

Leung T.Y., Wang Y., Ng W.C. and Leung K.M.Y., Proteomic characterization of biomarkers in a common marine biomonitor Perna viridis exposed to waterborne cadmium and hydrogen peroxide, The 5th international Conference on Marine Pollution and Ecotoxicology, 3-6 June 2007, City University of Hong Kong, Hong Kong. 2007.

 

Wang Y., Lam J.B.B., Liu J., Lam K.S.L., Cooper G.J.S. and Xu A., Adiponectin Plays Inhibitory Roles in the Proliferation and Tumor Development of Human MDA-MB-231 Breast Cancer Cells, 2nd Modern Drug Discovery & Development Summit. 2006.

 

Wang Y., Lam K.S.L. and Xu A., Adiponectin as a negative regulator in obesity-related mammary carcinogenesis. , Cell Research. 2007, 17: 280-2.

 

Wang Y., Lam K.S.L. and Xu A., Adiponectin as a therapeutic target for obesity-related metabolic and cardiovascular diseases., Drugs Development Research. 2006, 67: 677-686.

 

Wang Y., Lam J.B.B., Lam K.S.L., Liu J., Hoo R.L.C. and Xu A., Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. , Cancer Research. 2006, 66: 11462-70.

 

Wang Y., Lam J.B.B., Lam K.S.L., Liu J., Lam C.W., Hoo R.L.C., Wu D., Cooper G.J. and Xu A., Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice, Cancer Res. 2006, 66: 11462-70.

 

Wang Y., Lam K.S.L., Kraegen E.W., Sweeney G., Zhang J., Tso A.W.K., Chow W.S., Wat N.M.S., Xu J., Hoo R.L.C. and Xu A., Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans, Clin Chem. 2007, 53: 34-41.

 

Wang Y., Lam K.S.L. and Xu A., Lipocalin-2, a small lipid binding protein as an important mediator at the crossroad of obesity, inflammation and metabolic syndrome, Second International Symposium on Healthy Aging. 2007.

 

Wang Y., Lam K.S.L., Lam J.B.B., Lam C.W., Leung P.T.Y., Zhou M.Y. and Xu A., Overexpression of Angiopoietin-like Protein 4 Alters Mitochondria Activities and modulates methionine metabolic cycle in the liver tissues of db/db diabetic mice, Mol Endocrinol. 2007, 21: 972-86.

 

Wang Y., Lam K.S.L., Cooper G.J. and Xu A., Proteomic characterization of human serum proteins associated with the fat-derived hormone adiponectin. , Proteomics. 2006, 6: 3862-70.

 

Xu A., Wang Y. and Lam K.S.L., Adiponectin, In: Fantuzzi G & mazzone T, Adipose tissue and adipokines in health and disease. Totowa, New Jersey, Human press, 2007, 47-59.

 

Xu A., Tso A.W., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study, Circulation. 2007, 115: 1537-43.

 

Xu A., Tso A.W.K., Cheung B.M.Y., Wang Y., Wat N.M.S., Fong H.Y., Yeung C.Y., Janus E.D., Sham P.C. and Lam K.S.L., Circulating levels of adipocyte-fatty acid binding protein correlate with its adipose tissue expression and predict the development of the metabolic syndrome. , The Endocrine Society's 89th Annual Meeting, 2-5 June 2007, Toronto. 2007.

 

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.

 

 

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