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REN, Ee Chee Director, Graduate Affairs, BMRC, A*STAR; Principal Investigator, Singapore Immunology Network; Associate Professor, Department of Microbiology, NUS Phone: (65) 6516 3318 Email: [email protected] MAJOR RESEARCH INTERESTS Transcriptional Regulation of Hepatitis B Virus and Liver Cancer We have developed a model for infecting liver cancer cells using a HBV replicon under the control of the native viral promoter. Using this system we have identified a host liver factor – hnRNP K – that regulates HBV replication. A naturally occurring base substitution (SNP) in the viral core promoter interacts directly with hnRNP K and determines HBV replication efficiency (Ng et al, PLoS Med 2:e163, 2005). By accurately describing both viral and host components that contribute to viral replication, this combined approach will provide elucidation of pathways and specific genes that will form targets for the development of anti-HBV therapy. Another aspect of our hepatology related research is to identify HCC biomarkers. The development of hepatocellular carcinoma (HCC) is accompanied by a large number of chromosomal aberrations. While there are a number of analytical approaches to studying these genetic changes, they are often used singularly and hence provide an incomplete interpretation of the genome. To obtain a comprehensive view of such complex genetic changes occurring in tumour formation, we have employed a combinatorial approach of using expression profiling, G-banding, spectral karyotyping (SKY), comparative genomic hybridization (CGH), arrayCGH, fluorescence in situ hybridization (FISH) and ditag mapping to analyse a panel of human HCC tissues and cell lines. Results enabled a huge refinement to genomic interpretation and in addition to target gene identification, important new information such as fragile sites for chromosomal breakpoints, patient stratification etc can be derived. Immunogenetics and Determination of Immune Response by human MHC Our interest here is to determine the impact of MHC on the immune response. Studies using a dense SNP map of the 6 MB extended MHC region indicates extensive stretches of ancient MHC haplotypes that will provide a “fixed” group of immune response genes that can influence the overall immune response (Yu et al, Immunogenet 57: 559, 2005). We are also generating large numbers of crystal structures of specific HLA-peptide combinations to determine the binding rules for antigenic peptides which is the basis for the initiation of T cell responses. SELECTED PUBLICATIONS Ren EC. Know the enemy. Nature Biotech. 2006, 24: 330-331. Ng, LF, Barr I, Nyguyen T, Noor SM, Tan RS, Agathe LV, Gupta S, Khalil H, To TL, Hassan SS, Ren EC. Specific detection of H5N1 avian influenza A virus in field specimens by a one-step RT-PCR assay. BMC Infect Dis. 2006 6: 40. Lim S, Chan SH, Ren EC. Identification of a new HLA-A*2464 variant in the Singapore Chinese population. Tissue Antigens. 2006, 68: 265-267. Ng LF, Chan M, Chan SH, Cheng PC, Leung EH, Chen WN, Ren EC. Host heterogeneous ribonucleoprotein K (hnRNP K) as a potential target to suppress hepatitis B virus replication. PLoS Med. 2005; 2(7):e163. Yu HX, Chia JM, Bourque G, Wong MV, Chan SH, Ren EC. A population based LD map of the human chromosome 6p. Immunogenetics 2005; 57: 559-565. Yu HX, Srinivasan N, Ren EC, Chan SH. A11 Tetramer-assisted characterization of Rta-specific CD8+ T-cell responses in healthy virus carriers. Tissue Antigens. 2005; 65: 539-543. Hong P, Ng LF, Ren EC, Chen WN. A cell-based system for hepatitis B virus replication: significance of clinically enhanced viral replication in relation to deletions in viral core promoter. Front Biosci. 2005; 10: 2001-2004. Neo SY, Leow CY, Vinsensius B. Vega, Long PM ,Amirul Islam, Lai PBS, Liu E, Ren E C. Identification of discriminators of hepatocellular carcinoma vs. non- tumor liver using expression profiling. Hepatology, 2004; 39: 944-953.