INSTITUTE OF MOLECULAR BIOLOGY



Researcher : Chau JFL

List of Research Outputs

Chau J.F.L., Lee M.K., Law W.S., Chung S.K. and Chung S.S.M., Sodium/myo-inositol cotransporter-1 is essential for the development and function of the peripheral nerves, FASEB Journal. 2005, 19(13): 1887-1906.


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.


Project Title:Functional characterization of a putative tumour suppressor, AMP-activated protein kinase, in liver cancer
Investigator(s):Ching YP
Department:Pathology
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:02/2006
Abstract:
Purpose of study Liver cancer (hepatocellular carcinoma, HCC) is one of the most common cancers in the world, especially in Asia and Africa, and is the third most common fatal cancer in Hong Kong. While the risk factors are well defined, the underlying molecular mechanisms of HCC are still far from clear. Since the development of HCC is a multistep process, our long-standing interest is to identify tumour suppressor genes that play important roles in hepatocarcinogenesis. In our search, we have found that a hepatic kinase called AMP-activated protein kinase (AMPK), a key regulator for lipid and glucose metabolism in response to energy stress, is frequently downregulated in HCC cell lines and clinical samples (42%). Interestingly, recent discoveries have shown that tumour suppressors LKB1 and TSC2 lie upstream and downstream of AMPK, respectively, indicating that AMPK may be important in the regulation of cell growth, proliferation and apoptosis. Our pilot studies have also demonstrated that ectopic expression of the AMPK catalytic subunit in HepG2 cells significantly suppresses cell growth in colony formation assay. Conversely, HCC cell line with stable knockdown of AMPK catalystic subunit expression displays a much higher proliferation rate than that of the parental cell line (see research plan). These results suggest that AMPK possesses an activity to inhibit HCC cell growth. Here we propose to fully document the expression of AMPK and its effectors in HCC. We will explore the molecular basis of the underexpression of AMPK catalytic subunit in human HCC. We will also confirm the tumour suppressor activity of AMPK and delineate the molecular mechanisms by which loss of AMPK contributes to the formation of HCC. Findings derived from our work should shed important light on the pathogenesis of HCC and may provide novel targets for therapeutic intervention. Key issue and problem being address So far, the overall prognosis of HCC is unsatisfactory due to high incidence of recurrence and metastasis. It is therefore a high priority to unravel the molecular mechanisms underlying the pathogenesis of HCC so that better treatment modalities can be designed. In previous reports and our preliminary study, activation of AMPK has been demonstrated to play a role in suppressing the growth of cancer cells. These results prompt us to further address the pathogenic role of AMPK in HCC and to determine how dysregulation of AMPK leads to hepatocarcinogenesis. In this study, we will define the tumour suppressive function of AMPK in HCC and the regulatory roles of AMPK in cell signalling. Since AMPK is an important physiological regulator of cellular metabolism in response to nutrient stress and energy supply, our proposed study should advance our understanding on whether perturbation of energy metabolism can possibly linked to carcinogenesis. Results obtained in this study will derive novel insight on how the loss of AMPK function leads to the formation of cancer, aiming to provide opportunity for new molecular drug targets.


List of Research Outputs



Researcher : Chiu J

Project Title:Regulation of [alpha]-fetoprotein gene expression in differentiating and cancer cells
Investigator(s):Chiu J
Department:Institute of Molecular Biology
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:09/2002
Completion Date:12/2006
Abstract:
The project attempts to: (1) Identify and characterize DAS-binding protein (DAP) that regulate [alpha]-fetoprotein expression; (2) Investigate the specific DNA binding activity and biological function of DAP. The biological function will be determined by using various mutant genes, DAP antisense sequence and transcription factor decoys; (3) Identify other genes that are regulated by the DAS cis-element through a computer-assisted analysis of the genomic sequences in GenBank; and (4) Investigate the expression of these candidate genes in F9 cells during differentiation, and in developing liver cells and hepatomas.


Project Title:Biochemical and proteomic analyses of arsenic carcinogenesis
Investigator(s):Chiu J, Leung SY, He Q
Department:Institute of Molecular Biology
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:09/2003
Abstract:
To establish and examine the processes of in vitro carcinogenesis induced by arsenic; to identify key elements of oxidative stress that involve in arsenic-induced cell transformation by biochemical and proteomic approaches; to determine which signaling pathway that mediates arsenic-induced cell transformation by proteomic approach.


Project Title:Biochemical and proteomic analyses of arsenic carcinogenesis
Investigator(s):Chiu J, Leung SY, He Q
Department:Institute of Molecular Biology
Source(s) of Funding:Merit Award for RGC CERG Funded Projects
Start Date:09/2003
Abstract:
N/A


Project Title:Synergistic interaction of arsenic and HBV in the etiopathogenesis of hepatocellular carcinoma
Investigator(s):Chiu J
Department:Anatomy
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

Cai Z., Chiu J. and He Q., Current Progresses in Sample Preparation for Two-Dimensional Electrophoresis in Proteomics, Current Proteomics. 2006, 2: 259-268.
Wang Y., He Q., Che C.M. and Chiu J., Proteomic Characterization of the Cytotoxic Mechanism of Gold(III) Porphyrin 1a, an Potential Anticancer Drug, Proteomics. 2006, 6: 131-142.
Zhu R., Lau G., Chiu J. and He Q., Proteomics profiling of human serum for biomarker detection of the progression from hepatitis B virus to hepatocellular carcinoma, The 230th National Meeting of the American Chemical Society, Washington DC., Aug 28 - Sept 1. 2005.


Researcher : Chung SK

Project Title:Characterization of endothelin-1 gene manipulated mice for ischemic stroke, a leading cause of death and disability
Investigator(s):Chung SK
Department:Institute of Molecular Biology
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:09/2002
Completion Date:08/2006
Abstract:
The project attempts to determine if the ET-1 knockout mice have more severe ischemic brain injuries. The absolute and regional cerebral blood flow, neurological deficit, infarct volume and the detailed molecular signals will be determined.


Project Title:Molecular mechanisms of dementia associated with aging-related diseases, alzheimer's and multi-infarct
Investigator(s):Chung SK
Department:Institute of Molecular Biology
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:12/2003
Abstract:
To characterize of GET, TET or ETKO mice with human Swedish mutation in APP gene; to determine amyloidogenesis and neuropathological features in ET-1/mutant APPYAC brain; to determine memory deficit and brain activity in ET-1/mutant APPYAC mice; to determine the role of infarct and mutant APP on oxidative stress and neuropathogical features; to determine efficacy of ECE inhibitor and ETA and ETB receptors antagonists for neurotoxicity.


Project Title:Molecular mechanisms of dementia associated with aging-related diseases, alzheimer's and multi-infarct
Investigator(s):Chung SK
Department:Institute of Molecular Biology
Source(s) of Funding:Merit Award for RGC CERG Funded Projects
Start Date:12/2003
Abstract:
N/A


Project Title:Genetic approaches to understand the pathogenesis of diabetic neuropathy: common, debilitating disease
Investigator(s):Chung SK
Department:Institute of Molecular Biology
Source(s) of Funding:Merit Award for RGC CERG Funded Projects
Start Date:01/2005
Abstract:
N/A


Project Title:Genetic approaches to understand the pathogenesis of diabetic neuropathy: common, debilitating disease
Investigator(s):Chung SK
Department:Institute of Molecular Biology
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:01/2005
Abstract:
To determine contributions of AR and SD to the increased oxidative stress in diabetic nervous tissues; to determine the relationship between AR activity and the activation of NF-[kappa]B and PKC; to determine the contributions of vascular and nervous tissues to the diabetes-induced MNCV deficit; to determine the role of AR in the pathogenesis of chronic neuropathy by using the Thy1-YFP transgenic mice.


List of Research Outputs

Tang H.C., Leung G.P.H., Lo A.C.Y., Chung S.K., Man R.Y.K. and Vanhoutte P.M.G.R., Real-time quantitative PCR study of genes involved in the generation of endothelium-depedent contractions in the aorta of the spontaneously hypertensive rat, FASEB Journal. 2006, 20(4): A290-A291 Part 1.


Researcher : Chung SSM

Project Title:Osmoregulation in lens
Investigator(s):Chung SSM
Department:Institute of Molecular Biology
Source(s) of Funding:Outstanding RGC Projects
Start Date:09/1998
Abstract:
It is imperative to have a better understanding of the mechanisms leading to various cataracts such that preventive measures can be developed. Since maintaining the ionic strength and ionic composition in the lens is essential for the transparency of the lens, we plan to study the mechanism of osmoregulation in this organ. Transgenic mice that over-express aldose reductase and sodium dependent myoinositol transporter in their lenses will be used to increase the lens' level of sorbitol and myoinositol, respectively. We will determine if high level of these osmolytes causes cataract development, and see when the level of one osmolyte is high, will the lens compensate by reducing the level of other osmolytes. We will also determine whether high intracellular osmotic pressure affects the regulation of expression of genes that control the level of osmolytes such as aldose reductase, sodium dependent myoinositol transporter, and taurine transporter.


Project Title:Effects of early postnatal feeding on fatty acid metabolism
Investigator(s):Chung SSM, Sheng HP
Department:Institute of Molecular Biology
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:11/2002
Abstract:
Both epidemiological studies and animal studies have shown that prenatal and early postnatal nutrition not only affects infant growth and development, it also predetermines future metabolism, performance adn morbidity. This study addresses the problems of nutritional environment during the sucking period on lipid metabolism and later-life obesity.


Project Title:Polyol pathway in diabetic dyslipidemia
Investigator(s):Chung SSM
Department:Institute of Molecular Biology
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:01/2003
Abstract:
To determine if AR null mutation reduces plasma TG levels in diabetic mice; to determine if ARI reduces plasma TG in diabetic mice; to determine if AR null mutation or ARI nor ARI normalizes LDL and HDL leviabetic mice.


Project Title:Mechanism of Nogo-A inhibition of axonal regeneration
Investigator(s):Chung SSM, Chung SK, Ju G.
Department:Institute of Molecular Biology
Source(s) of Funding:NSFC/RGC Joint Research Scheme
Start Date:01/2003
Abstract:
To develop Nogo gene knockout mice to determine the role of this gene in the inhibition of axonal regeneration and its physiological functions; to develop transgenic mice that overexpress Nogo-A in their Schwann cells to determine if that would make their PNS non-permissive for axonal regeneraton; to develop transgenic mice that overexpress mutant Nogo-A with the Nogo-66 or aa623-640 region deleted to determine which domain is responsible for the inhibitory effect of Nogo-A.


Project Title:The polyol pathway as a thrifty pathway promoting energy storage
Investigator(s):Chung SSM
Department:Physiology
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:09/2003
Abstract:
To determine the in vivo conversion of glucose to fatty acids and triglycerides in normal mice and mice deficient in AR; to determine if AR deficiency affects the activities of lipogenic/adipogenic transcriptional factors including ADD1/SREBP-1 and CHOP-C/EBP-[alpha], anti-obesity transcriptional factor FOXC2, and enzymes fatty acid synthase (FAS) and stearoyl CoA desaturase (SCD); to assess whether administration of inhibitors of aldose reductase (ARI) will affect obesity and improve glucose tolerance in the agouti yellow mice; to determine whether the effects of aldose reductase deficiency on agouti-induced lipogenesis and obesity can be duplicated in diet-induced obesity models.


Project Title:The polyol pathway as a thrifty pathway promoting energy storage
Investigator(s):Chung SSM
Department:Physiology
Source(s) of Funding:Merit Award for RGC CERG Funded Projects
Start Date:09/2003
Abstract:
N/A


Project Title:Aldose reductase in diabetic cataract
Investigator(s):Chung SSM
Department:Institute of Molecular Biology
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:10/2004
Abstract:
To determine if the antioxidant can prevent AR-induced slow-developing cataract; to determine the osmolyte content and oxidative status of the slow-developing cataract; to compare the morphological changes in the acute diabetic cataract and the slow developing cataract; to determine if there is apoptosis in the epithelial cells of the precataractous lenses.


Project Title:Aldose reductase in diabetic cataract
Investigator(s):Chung SSM
Department:Institute of Molecular Biology
Source(s) of Funding:Merit Award for RGC CERG Funded Projects
Start Date:01/2005
Abstract:
N/A


Project Title:The role of OREBP in renal osmoprotection and its contribution to chronic cyclosporine A nephrotoxicity
Investigator(s):Chung SSM
Department:Institute of Molecular Biology
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

Wong K.W., Chiu P., Chung S.S.M., Chow L.M., Zhao Y.Z., Yang B. and Ko C.B., Pseudolaric Acid B, a novel microtubule-destabilizing agent that circumvents multi-drug resistance phenotype and exhibits antitumor activity in vivo., Clinical Cancer Research. 2005, 11: 6002-11.


Researcher : Fung KL

List of Research Outputs

Cheung A.K.H., Fung K.L., Lo A.C.Y., Lam T.L., So K.F., Chung S.S.M. and Chung S.K., Aldose reductase deficiency prevents diabetes-induced blood retinal barrier breakdown, apoptosis and glial reactivation in the retina of db/db mice, Diabetes. 2005, 54(11): 3119-25.


Researcher : He ML

List of Research Outputs

Qian W.P., Tan Y., Chen Y., Peng Y., Li Z., Lu G.X., Lin M.C., Kung H., He M.L. and Shing L.K., Rapid quantification of semen hepatitis B virus DNA by real-time polymerase chain reaction, World Journal of Gastroenterology. 2005, 11(34): 5385-9.


Researcher : Jin D

Project Title:Implementation of theoretical and technical system for disease genomics
Investigator(s):Jin D
Department:Institute of Molecular Biology
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:Institute of Molecular Biology
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 Health, US Department of Health and Human Services - General Award
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



Researcher : Ko CB

Project Title:Transgenic mice approach to elucidating the role of osmotic response element binding protein (OREBP) in water homeostasis
Investigator(s):Ko CB, Chung SSM
Department:Chemistry
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:09/2002
Completion Date:08/2005
Abstract:
The project aims at understanding the physiological role of osmotic response element binding protein (OREBP) in kidney by developing transgenic mice that overexpress a dominant negative mutant of this protein in the inner medullary collecting ducts. It is anticipated that this study would reveal the role of OREBP in urine concentrating mechanism.


Project Title:Mechanism of nucleocytoplasmic shuttling of OREBP/TonEBP
Investigator(s):Ko CB, Chung SSM
Department:Chemistry
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:09/2003
Completion Date:01/2007
Abstract:
To elucidate the role of Crm-1 in hypotonicity-induced nuclear export of OREBP; to define the minimal domain in OREBP required for the nuclear import and export functions; to examine the role of histone deacetylases in regulation of hypotonicity-induced OREBP nuclear export.


Project Title:Mechanism of nucleocytoplasmic shuttling of OREBP/TonEBP
Investigator(s):Ko CB, Chung SSM
Department:Chemistry
Source(s) of Funding:Merit Award for RGC CERG Funded Projects
Start Date:09/2003
Completion Date:01/2007
Abstract:
N/A


Project Title:The role of osmotic response element binding protein in the hypertonic induction of p53
Investigator(s):Ko CB
Department:Chemistry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:02/2004
Completion Date:01/2006
Abstract:
To elucidate the role of OREBP in the phypertonic-induction of p53, and to explore the role of p53 in mediating the expression of OREBP-dependent genes.


Project Title:The mechanism of OREBP/TonEBP/NFAT5-dependent transcription - role of signaling pathway and chromatin remodeling
Investigator(s):Ko CB
Department:Chemistry
Source(s) of Funding:Merit Award for RGC CERG Funded Projects
Start Date:01/2005
Abstract:
N/A


Project Title:The mechanism of OREBP/TonEBP/NFAT5-dependent transcription - role of signaling pathway and chromatin remodeling
Investigator(s):Ko CB, Chung SSM, Rao A.
Department:Chemistry
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:01/2005
Abstract:
To examine the correlation between OREBP-recruitment to different promoters and the kinetics of OREBP-dependent gene expressions; to evaluate the role of histone modification in OREBP-dependent gene transcription and the role of IKK and p38 in histone phosphorylation at OREBP-dependent promoters; to investigate the role of p300/CBP in histone modification and OREBP transcription activation.


Project Title:To investigate the role of OREBP/TonEBP/NFAT5 in adipocyte growth and function
Investigator(s):Ko CB
Department:Chemistry
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 Role of OREBP in Cell Growth
Investigator(s):Ko CB
Department:Chemistry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:01/2006
Completion Date:10/2006
Abstract:
Cell growth, together with cell division and cell death is one of the most fundamental aspects of cell behavior. Proliferating cells often double in mass by increased marcomolecular biosynthesis before division to ensure cell size is maintained. Although the term cell growth (increase in mass and size) and cell division (progression through the cell cycle and the increase in number) are often being used synonymously, they are indeed separable process (1). In mammalian cells, blocking cell cycle progression did not prevent cells from increase in size (2). On the other hand, it is conceivable that cells must attain a threshold of size before committed to cell division to achieve cell-size homeostasis. Cell growth and division are therefore tightly coordinated in most dividing cells during animal development. Yet how cell growth is linked to cell cycle progression is still poorly understood. Prevailing hypothesis suggested that cell growth (mass or size) is rate-limiting for cell cycle progression. This is supported by the fact that blocking cell growth by nutrient or growth factor deprivation results in cell cycle arrest at G1 phase (3). Molecularly, it has been suggested that cell cycle progression is triggered by the increase in translation rate, particularly that of cell cycle regulators (4,5). Furthermore, p53, Retinoblastoma, and p16ARF are implicated as signaling molecules to coordinate cell growth and division by virtue of their roles in regulating both synthesis of ribosome and cell cycle progression (6). The Osmotic Response Element Binding Protein (OREBP), also known as NFAT5 or TonEBP, was originally identified as a transcription factor that orchestrates the hypertonicity-induced expression of a battery of genes crucial for the adaptation of mammalian cells to extracellular hypertonic stress (7). The known OREBP-regulated gene, such as aldose reductase, myo-inotistol transporter, betaine transporter, etc, are responsible for the intracellular accumulation of organic osmolytes (such as polyols and amino acid derivatives) that are important for cells to withstand extracellular hypertonic stress. In the course of elucidating the role of OREBP in lens development, we revealed that inhibition of OREBP activity leads to incomplete elongation of lens fiber cells (8). Since the lens fiber cells are terminally differentiated, yet are directed to elongate significantly to complete the growth process, our data implicated a role of OREBP in cell growth of lens fiber cells. Recent data from us demonstrated that OREBP silencing in HeLa cells also decreases cell size (data not shown). Taken together, these data suggested that OREBP may also play a role in cell growth. How OREBP activity is required for cell growth is unknown at present. We suggested the following possibilities: 1) OREBP silencing may lead to overall reduced level of intracellular osmolytes, resulting in cell shrinkage and growth deficit. 2) OREBP silencing may reduce the expression level of sodium-coupled neutral amino acid transporter subtype SNAT2, which may play a dominant role in the cell growth. SNAT2 is a member of the SLC38 gene family. Together with other transporter subtypes including SNAT1 and SNAT4, it accounts for the classical System A transport activity and is responsible for the cellular transport of small, zwitterionic amino acids. Hypertonic induction of SNAT2 is OREBP-dependent (9), and is thought to be important for the maintenance of cell volume, as SNAT2 gene silencing hinders cell recovery from hypertonic stress (10). Furthermore, SNAT2 is also subjected to tight regulatory control by amino acid deprivation and cell cycle progression. In myotubes, adipocyctes, fibroblasts and HepG2 cells, amino acid deprivation leads to rapid redistribution to the SNAT2 protein from an intracellular compartment to the plasma membrane, as well as an increase in gene transcription (11-14). Besides serving as organic osmolytes, the level of intracellular amino acids also acts as the activator for the mTOR (mammalian target of rapamycin) pathway (15). The mTOR pathway has emerged as one of the key regulators of cell growth in mammals (16). It couples the input of growth factor, nutrients (amino acids and glucose), and energy status to S6 Kinase 1 (S6K1) activation, translational initiation and cell growth. Although the mTOR pathway is most sensitive to change in leucine levels, a decrement in level of various other amino acids also inhibits the pathway (17), suggesting that the level of total amino acid pool is important for the pathway and cell growth. Inhibition of the pathway by rapamycin (a specific inhibitor of mTOR) resulting in reduced protein synthesis, leading to reduced cell size (18). 3) OREBP silencing may lead to DNA damage, resulting in stalled cell growth. Expression of dominant-negative OREBP leads to DNA damage, p53 overexpression and Chk2 activation in growing lens fiber cells with the cause that is not yet evident (8). However, it is still unknown if OREBP silencing leads to similar defects in HeLa cells. In proliferating cells, DNA damage activates Chk1 or Chk2, which plays an important role in organizing DNA damage response including stabilization of p53 and phosphorylation of Cdc25A and Cdc25C proteins, resulting in cell cycle arrest at G1/S or G2/M or apoptosis (19,20). In this proposal, we propose to discern the molecuclar mechanism leading to the observed defect in OREBP knockdown cells. There are two major objectives for the study: 1. To fully characterize the cell size phenotype in OREBP knockdown cells. 2. To examine the mechanism(s) responsible for the cell growth deficit in OREBP knockdown cells. The findings from this study will provide us more information regarding the function of OREBP in relation to cell growth, and will enable us to perfect our grant proposal in the coming CERG application. Reference 1.Jorgensen, P., and Tyers, M. (2004) Curr Biol 14, R1014-1027 2.Conlon, I. J., Dunn, G. A., Mudge, A. W., and Raff, M. C. (2001) Nat Cell Biol 3, 918-921 3.Pardee, A. B. (1974) Proc Natl Acad Sci U S A 71, 1286-1290 4.Daga, R. R., and Jimenez, J. (1999) J Cell Sci 112 Pt 18, 3137-3146 5.Polymenis, M., and Schmidt, E. V. (1997) Genes Dev 11, 2522-2531 6.Ruggero, D., and Pandolfi, P. P. (2003) Nat Rev Cancer 3, 179-192 7.Handler, J. S., and Kwon, H. M. (2001) Kidney Int 60, 408-411 8.Wang, Y., Ko, B. C., Yang, J. Y., Lam, T. T., Jiang, Z., Zhang, J., Chung, S. K., and Chung, S. S. (2005) J Biol Chem 280, 19986-19991 9.Trama, J., Go, W. Y., and Ho, S. N. (2002) J.Immunol. 169, 5477-5488 10.Bevilacqua, E., Bussolati, O., Dall'Asta, V., Gaccioli, F., Sala, R., Gazzola, G. C., and Franchi-Gazzola, R. (2005) FEBS Lett 579, 3376-3380 11.Bain, P. J., LeBlanc-Chaffin, R., Chen, H., Palii, S. S., Leach, K. M., and Kilberg, M. S. (2002) J Nutr 132, 3023-3029 12.Gazzola, R. F., Sala, R., Bussolati, O., Visigalli, R., Dall'Asta, V., Ganapathy, V., and Gazzola, G. C. (2001) FEBS Lett 490, 11-14 13.Hyde, R., Christie, G. R., Litherland, G. J., Hajduch, E., Taylor, P. M., and Hundal, H. S. (2001) Biochem J 355, 563-568 14.Ling, R., Bridges, C. C., Sugawara, M., Fujita, T., Leibach, F. H., Prasad, P. D., and Ganapathy, V. (2001) Biochim Biophys Acta 151, 15-21 15.Kim, D. H., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument-Bromage, H., Tempst, P., and Sabatini, D. M. (2002) Cell 110, 163-175 16.Sarbassov, D. D., Ali, S. M., and Sabatini, D. M. (2005) Curr Opin Cell Biol 17, 1-8 17.Hara, K., Yonezawa, K., Weng, Q. P., Kozlowski, M. T., Belham, C., and Avruch, J. (1998) J Biol Chem 273, 14484-14494 18.Fingar, D. C., Salama, S., Tsou, C., Harlow, E., and Blenis, J. (2002) Genes Dev 16, 1472-1487 19.Ahn, J., Urist, M., and Prives, C. (2004) DNA Repair (Amst) 3, 1039-1047 20.Agarwal, M. L., Taylor, W. R., Chernov, M. V., Chernova, O. B., and Stark, G. R. (1998) J Biol Chem 273, 1-4


List of Research Outputs



Researcher : Kung H

List of Research Outputs

Adler V., Qu Y., Smith S.J., Izotova L., Pestka S., Kung H., Lin M.C., Friedman F.K., Chie L., Chung D., Boutjdir M. and Pincus M.R., Functional interactions of Raf and MEK with Jun-N-Terminal Kinase (JNK) result in a positive feedback loop on the oncogenic Ras signaling pathway, Biochemistry. 2005, 44(32): 10784-10795.
Gu Q., Xia H.H.X., Wang J., Chan O.O., Lai K.C., Fung F.M.Y., Wong K.W., Cheung K.L., Kung H. and Wong B.C.Y., Update on clarithromycin resistance in Helicobacter pylori in Hong Kong and its effect on clarithromycin-based triple therapy., In: Gu Q, Xia HHX, Wang JD, Chan AOO, Lai KC, Chan CK, Yuen MF, Fung FMY, Wong KW, Cheung HKL, H.F. Kung HF, B.C.Y. Wong BCY.. , J Gastroenterol Hepatol . 2005, 20 (Suppl.): A160.
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.
Qian W.P., Tan Y., Chen Y., Peng Y., Li Z., Lu G.X., Lin M.C., Kung H., He M.L. and Shing L.K., Rapid quantification of semen hepatitis B virus DNA by real-time polymerase chain reaction, World Journal of Gastroenterology. 2005, 11(34): 5385-9.
Sun Y., Wang J., Xia H.H.X., Zou B., Lin M.C., Kung H. and Wong B.C.Y., Interferon-β-induced expression of XAF1 requires phosphorylation of STAT1 and a sequential activation of protein kinase C and JNK in colon cancer. Digestive Disease Week 2006, 20-25 May, Los Angeles, USA , Gastroenterology. 2006, 4 Suppl 2: A671.
Sun Y., Xia H.H.X., Zhu S., Zou B., Lin M.C., Kung H. and Wong B.C.Y., Novel interaction between xiap-associated factor 1 (XAF1) and nuclear coactivator CBP in colon cancer. Digestive Disease Week 2006, 20-25 May, Los Angeles, USA , Gastroenterology. 2006, 4 Suppl 2: A680.
Wong B.C.Y., Chan O.O., Wong R.W.M., Hui W.M., Kung H. and Lam S.K., Attitudes and knowledge of colorectal cancer and screening in Hong Kong – A population-based study, Journal of Gastroenterology and Hepatology. 2006, 21(1 Pt 1): 41-46.
Zou B., Lin M.C., Lam S.K., Tu S., Zeng H., Yang Y., Wang J., He H., Jiang S.H., Kung H. and Wong B.C.Y., Distinguished Poster Award, "Hypermethylation status around exon 1 of XIAP-Associated Factor 1(XAF1) in human gastric and colon cancer cell line.", Asian Pacific Digestive Week, Sept. 25-28, Seoul, Korea.. 2005.
Zou B., Lin M.C., Lam S.K., Tu S., Zeng H., Yang Y., Wang J., He H., Jiang S.H., Kung H. and Wong B.C.Y., Hypermethylation status around exon 1 of XIAP-Associated Factor 1(XAF1) in human gastric and colon cancer cell line. Asian Pacific Digestive Week, Sept. 25-28, 2005, Seoul, Korea. , Journal of Gastroenterology and Hepatology. 2005, 20: Supp A370.


Researcher : Lam TL

List of Research Outputs

Cheung A.K.H., Fung K.L., Lo A.C.Y., Lam T.L., So K.F., Chung S.S.M. and Chung S.K., Aldose reductase deficiency prevents diabetes-induced blood retinal barrier breakdown, apoptosis and glial reactivation in the retina of db/db mice, Diabetes. 2005, 54(11): 3119-25.


Researcher : Law WS

List of Research Outputs

Chau J.F.L., Lee M.K., Law W.S., Chung S.K. and Chung S.S.M., Sodium/myo-inositol cotransporter-1 is essential for the development and function of the peripheral nerves, FASEB Journal. 2005, 19(13): 1887-1906.


Researcher : Lee MK

List of Research Outputs

Chau J.F.L., Lee M.K., Law W.S., Chung S.K. and Chung S.S.M., Sodium/myo-inositol cotransporter-1 is essential for the development and function of the peripheral nerves, FASEB Journal. 2005, 19(13): 1887-1906.


Researcher : Lin MC

Project Title:Basic research on systemic damage in early stage and wound-healing after severe trauma
Investigator(s):Lin MC
Department:Institute of Molecular Biology
Source(s) of Funding:Matching Fund for National Key Basic Research Development Scheme (973 Projects)
Start Date:04/2001
Abstract:
To study basic research on systemic damage in early stage and wound-healing after severe trauma.


Project Title:Basic research on the mechanism of aging and the prevention of geriatric disease
Investigator(s):Lin MC
Department:Institute of Molecular Biology
Source(s) of Funding:Matching Fund for National Key Basic Research Development Scheme (973 Projects)
Start Date:12/2001
Abstract:
To study the mechanism of aging and the prevention of geriatric disease.


Project Title:Characterization of a novel cell cycle related kinase in glioblastoma
Investigator(s):Lin MC, Leung SY, Ching YP
Department:Institute of Molecular Biology
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:12/2002
Abstract:
The project aims at characterizing the role of cell cycle related kinase (CCRK) in cell cycle control, apoptosis, cell division and cell proliferation. Potential tumorigenic function of CCRK in human glioblastoma, fibroblast cell lines, and nude mice xenograft will also be investigated.


Project Title:Cancer gene therapy using a novel anti-cancer polypeptide hTERTC27 delivered by a novel AAV and Adenovirus Cocktail vector system
Investigator(s):Lin MC, Wong BCY, Kung H, Peng Y
Department:Institute of Molecular Biology
Source(s) of Funding:Innovation and Technology Support Programme
Start Date:06/2003
Completion Date:08/2006
Abstract:
To optimize our innovative, novel and patented hTERTC27 cancer gene therapy and the AAV/Adv cocktail vector technologies developed in our laboratory; to establish patented stable cell line and platforms for the large scale production of AAV-hTERTC27 and Adv-hTERTC27; to carry out, using the above, in pre-clinical study for treating solid tumors.


Project Title:Molecular basis of alcohol-induced birth defects, the critical role of Pax 6
Investigator(s):Lin MC, Wong BCY, Yang JY, Peng Y
Department:Institute of Molecular Biology
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:09/2003
Abstract:
To elucidate the signaling pathways leading to alcohol-mediated inhibition of Pax6 expression and to identify the targets downstream of Pax6 responsible for microcephaly. We are particularly interested in the involvements of the PI3 kinase pathways and the reactive oxygen species and reactive nitrogen species; to investigate the molecular mechanisms for alcohol-induced growth retardation, in particular its relationship with gut development; to study alcohol induced eye deformation; to screen for agents that protect against alcohol induced birth defects.


Project Title:Molecular basis of alcohol-induced birth defects, the critical role of Pax 6
Investigator(s):Lin MC, Wong BCY, Yang JY, Peng Y
Department:Institute of Molecular Biology
Source(s) of Funding:Merit Award for RGC CERG Funded Projects
Start Date:09/2003
Abstract:
N/A


Project Title:Molecular basis for the telomere dysfunction and anti-tumor activities of a C-terminal polypeptide of human telomerase reverse transcriptase (hTERTC27)
Investigator(s):Lin MC, Wong BCY
Department:Institute of Molecular Biology
Source(s) of Funding:Merit Award for RGC CERG Funded Projects
Start Date:12/2003
Completion Date:11/2005
Abstract:
N/A


Project Title:Gene therapy for the treatment of HBV infection, HBV-induced liver cancer
Investigator(s):Lin MC, Zheng B, Yuen KY, Kung H
Department:Institute of Molecular Biology
Source(s) of Funding:Innovation and Technology Support Programme
Start Date:07/2004
Completion Date:11/2005
Abstract:
To develop an innovative and effective gene therapies to treat HBV infection and HCC.


Project Title:Development of Novel AAV based anti-angiogenesis gene therapy for the treatment of liver cancer
Investigator(s):Lin MC, Fan ST, Wong BCY, Ng SM, He ML, Gan R.B., Kung H
Department:Institute of Molecular Biology
Source(s) of Funding:Innovation and Technology Support Programme
Start Date:08/2004
Completion Date:11/2005
Abstract:
To develop an innovative and effective gene therapies to treat hepatocellular carcinoma (HCC).


Project Title:Cancer gene therapy using a novel anti-cancer polypeptide hTERTC27 delivered by a novel AAV and Adenovirus Cocktail vector system
Investigator(s):Lin MC, Kung H, Wong BCY
Department:Institute of Molecular Biology
Source(s) of Funding:Innovation and Technology Fund Internship Programme
Start Date:09/2004
Completion Date:07/2005
Abstract:
To optimize our innovative, novel and patented hTERTC27 cancer gene therapy and the AAV/Adv cocktail vector technologies developed in our laboratory; to establish patented stable cell line and platforms for the large scale production of AAV-hTERTC27 and Adv-hTERTC27; to carry out, using the above, in pre-clinical study for treating solid tumors.


Project Title:Characterizing the role of P13K signaling cascade in Xenopus neural induction
Investigator(s):Lin MC
Department:Institute of Molecular Biology
Source(s) of Funding:Merit Award for RGC CERG Funded Projects
Start Date:01/2005
Abstract:
N/A


Project Title:Characterization of HNF-1 Cis-element as a novel insulin negative responsive element and identification of a new anti-diabetic drug targeting this element
Investigator(s):Lin MC
Department:Institute of Molecular Biology
Source(s) of Funding:Merit Award for RGC CERG Funded Projects
Start Date:01/2006
Abstract:
N/A


Project Title:Characterization of HNF-1 Cis-element as a novel insulin negative responsive element and identification of a new anti-diabetic drug targeting this element
Investigator(s):Lin MC, Lu L, Tam S
Department:Institute of Molecular Biology
Source(s) of Funding:Competitive Earmarked Research Grants (CERG)
Start Date:01/2006
Abstract:
To determine if the consensus HNF-1 element also displays negative insulin responsiveness; to determine the role of HNF1α versus HNF1β and mutant HNF-1α in this transcription regulation; to evaluate the therapeutic effects / molecular mechanisms of a new anti-diabetic drug targeting this INRE.


Project Title:System biology study of a novel anti-angiogenesis polypeptide kringle 1 domain of hepatocyte growth factor
Investigator(s):Lin MC, Yiu SM
Department:Chemistry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:03/2006
Abstract:
Kringle domain, a protein module consists of 80 amino acids, function as recognition units for binding of other proteins in solution and on cells. Several of the kringle domain peptide including Angiostatin has been shown to exhibit anti-angiogenesis effect. Recently, my laboratory studied the cancer therapeutic effect of a novel anti-angiogenesis polypeptide, kringle 1 domain of human hepatocyte growth factor (HGFK1). We demonstrated that using a recombinant adeno-associated virus (AAV) carrying the HGFK1 gene (rAAV-HGFK1), we can significantly inhibited the proliferation, migration, and vessel tube formation of mice microvascular endothelial cells in vitro. More importantly, in an in vivo preclinical study conducted in rat orthotropic model of hepatocellular carcinoma (HCC), we showed that rAAV-HGFK1 is more potent than rAAV-Endostatin, the leading anti-angiogenesis gene, in prolonging the survival rate of the tumor bearing rats. Furthermore, rAAV-HGFK1 effectively inhibits tumor growth and metastasis. The objectives of the research proposal is to elucidate the molecular mechanisms underlie the anti-angiogenesis effect of HGFK1 polypeptide using System Biology approach, which will use bioinformatics to integrate data obtained from cDNA microarray experiments, Yeast two hybrid and Proteomic study. Multiple anti-angiogenesis molecules with different efficacies have been identified, however their underlying molecular mechansims remain elusive. These molecules potentially exert their effects through different signal pathways, with different interacting proteins and downstream targets. Information gained from this study will allow us to compare the molecular mechanisms of HGFK1 to that of the current leading anti-angiogenesis polypeptide Endostatin which has recently been reported using similar approaches (Abdollahi, A et al. Molecular Cell 13: 649-663, 2004).


List of Research Outputs

Adler V., Qu Y., Smith S.J., Izotova L., Pestka S., Kung H., Lin M.C., Friedman F.K., Chie L., Chung D., Boutjdir M. and Pincus M.R., Functional interactions of Raf and MEK with Jun-N-Terminal Kinase (JNK) result in a positive feedback loop on the oncogenic Ras signaling pathway, Biochemistry. 2005, 44(32): 10784-10795.
Qian W.P., Tan Y., Chen Y., Peng Y., Li Z., Lu G.X., Lin M.C., Kung H., He M.L. and Shing L.K., Rapid quantification of semen hepatitis B virus DNA by real-time polymerase chain reaction, World Journal of Gastroenterology. 2005, 11(34): 5385-9.
Sun Y., Wang J., Xia H.H.X., Zou B., Lin M.C., Kung H. and Wong B.C.Y., Interferon-β-induced expression of XAF1 requires phosphorylation of STAT1 and a sequential activation of protein kinase C and JNK in colon cancer. Digestive Disease Week 2006, 20-25 May, Los Angeles, USA , Gastroenterology. 2006, 4 Suppl 2: A671.
Sun Y., Xia H.H.X., Zhu S., Zou B., Lin M.C., Kung H. and Wong B.C.Y., Novel interaction between xiap-associated factor 1 (XAF1) and nuclear coactivator CBP in colon cancer. Digestive Disease Week 2006, 20-25 May, Los Angeles, USA , Gastroenterology. 2006, 4 Suppl 2: A680.
Yu L., Wang J., Zou B., Lin M.C., Wu Y.L. and Wong B.C.Y., Sulindac Metabolites Induces XAF1 Expression by Inhibition of Extracellular Signal-regulated Kinase 1/2 Phosphorylation in Human Gastric Cancer Cells. Oral presentation, Asian Pacific Digestive Week 2005, Sept. 25-28, 2005, Seoul, Korea , Journal of Gastroenterology and Hepatology. 2005, 20: Supp A299.
Zou B., Chim J.C.S., Lin M.C., Zeng H., He H., Yu L., Sun Y., Jiang S.H. and Wong B.C.Y., Correlation between the single-site CpG mutation within the gene promoter and the expression silencing of XIAP -Associated Factor 1 (XAF1) in human colon cancer cell lines. Asian Pacific Digestive Week, Sept. 25-28, 2005, Seoul, Korea., Journal of Gastroenterology and Hepatology. 2005, 20: Supp A253.
Zou B., Chim J.C.S., Lin M.C., Zeng H., He H., Yu L., Sun Y., Jiang S.H. and Wong B.C.Y., Distinguished Poster Award, "Correlation between the single-site CpG mutation within the gene promoter and the expression silencing of XIAP -Associated Factor 1 (XAF1) in human colon cancer cell lines" , Asian Pacific Digestive Week, Sept. 25-28, Seoul, Korea. 2005.
Zou B., Lin M.C., Lam S.K., Tu S., Zeng H., Yang Y., Wang J., He H., Jiang S.H., Kung H. and Wong B.C.Y., Distinguished Poster Award, "Hypermethylation status around exon 1 of XIAP-Associated Factor 1(XAF1) in human gastric and colon cancer cell line.", Asian Pacific Digestive Week, Sept. 25-28, Seoul, Korea.. 2005.
Zou B., Lin M.C., Lam S.K., Tu S., Zeng H., Yang Y., Wang J., He H., Jiang S.H., Kung H. and Wong B.C.Y., Hypermethylation status around exon 1 of XIAP-Associated Factor 1(XAF1) in human gastric and colon cancer cell line. Asian Pacific Digestive Week, Sept. 25-28, 2005, Seoul, Korea. , Journal of Gastroenterology and Hepatology. 2005, 20: Supp A370.


Researcher : Lo ACY

List of Research Outputs

Tang H.C., Leung G.P.H., Lo A.C.Y., Chung S.K., Man R.Y.K. and Vanhoutte P.M.G.R., Real-time quantitative PCR study of genes involved in the generation of endothelium-depedent contractions in the aorta of the spontaneously hypertensive rat, FASEB Journal. 2006, 20(4): A290-A291 Part 1.


Researcher : Lok CN

Project Title:Chemical biology of silver nanoparticles
Investigator(s):Lok CN, Chiu J, Che CM
Department:Institute of Molecular Biology
Source(s) of Funding:Small Project Funding
Start Date:11/2004
Completion Date:04/2006
Abstract:
To formulate of biocompatible silver nanoparticles and to investigate their biological properties.


List of Research Outputs



Researcher : Ma H

List of Research Outputs

Xu R., Rahimi M., Ma H., Fung P.C.W., Chang C., Xu S. and During M., Stability of infectious recombinant adeno-associated viral vector in gene delivery, Medical Science Monitor. 2005, 11: 305-308.


Researcher : Ng SM

Project Title:Molecular cloning and functional characterization of the human cell cycle related kinase-interacting proteins
Investigator(s):Ng SM, Lin MC
Department:Chemistry
Source(s) of Funding:Small Project Funding
Start Date:12/2005
Abstract:
1. To clone the genes encoding the proteins that specifically interact with CCRK in a yeast two-hybrid screening. 2. To elucidate the functional roles of the CCRK-interacting proteins in glioblastoma carcinogenesis.


List of Research Outputs



Researcher : Peng Y

List of Research Outputs

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.
Qian W.P., Tan Y., Chen Y., Peng Y., Li Z., Lu G.X., Lin M.C., Kung H., He M.L. and Shing L.K., Rapid quantification of semen hepatitis B virus DNA by real-time polymerase chain reaction, World Journal of Gastroenterology. 2005, 11(34): 5385-9.


Researcher : Tan Y

List of Research Outputs

Qian W.P., Tan Y., Chen Y., Peng Y., Li Z., Lu G.X., Lin M.C., Kung H., He M.L. and Shing L.K., Rapid quantification of semen hepatitis B virus DNA by real-time polymerase chain reaction, World Journal of Gastroenterology. 2005, 11(34): 5385-9.


Researcher : Wong CM

List of Research Outputs

Cheung B.M.Y., Lo J.L., Fong H.Y., Chan M.Y., Wong S.H., Wong C.M., Lam K.S.L., Lau C.P. and Karlberg J.P.E., Randomised controlled trial of qigong in the treatment of mild essential hypertension, J Hum Hypertens. 2005, 19: 697-704.


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

Dai J., Rabie A.B.M. and Xu R., AAV mediated VEGF gene therapy to control mandibular condylar growth, 20th International Association for Dental Research (South-East Asian Division). 2005, Abs No. Poster IP102.
Lee K.W., Man K., Ho J.W.Y., Wang X., Poon R.T.P., Xu Y., Ng T.P., Chu A.C.Y., Sun K.W., Ng I.O.L., Sun H.C., Tang Z.Y., Xu R. and Fan S.T., FTY720: a promising agent for treatment of metastatic hepatocellular carcinoma, Clinical Cancer Research. 2005, 11(23): 8458-8466.
Tsui T.Y., Lau C.K., Ma J., Wu X., Wang Y., Farkas S., Xu R., Schlitt H.J. and Fan S.T., rAAV-mediated stable expression of heme oxygenase-1 in stellate cells: a new approach to attenuate liver fibrosis in rats, Hepatology. 2005, 42(2): 335-342.
Xu R., Rahimi M., Ma H., Fung P.C.W., Chang C., Xu S. and During M., Stability of infectious recombinant adeno-associated viral vector in gene delivery, Medical Science Monitor. 2005, 11: 305-308.


Researcher : Yeung CM

List of Research Outputs

Yeung C.M., An B.S., Cheng C.K., Chow B.K.C. and Leung C.K., Expression and transcriptional regulation of the GnRH receptor gene in human neuronal cells., Mol. Hum. Reprod.. 2005, 11(11): 837-842.


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