Molecular genetics and infectomics
The main interest of the team in the Human Genome Laboratory is the isolation and characterization of novel human genes and proteins. Thus far, several novel genes have been isolated and analysed. The first gene, HEP-COP isolated from the Hep3B hepatocellular carcinoma cell line, is the human homologue of the 160 kD alpha-subunit of the coatomer protein complex. The HEP-COP gene on chromosome 1q23-q25 codes for the largest of seven membrane coat proteins (COP) comprising the coatomer which mediates intracellular transport of secretory proteins between the Golgi apparatus and the endoplasmic reticulum. The 25 N-terminal amino acids of HEP-COP are identical to xenin, a gastrointestinal hormone that stimulates exocrine pancreatic secretion.

The second gene was designated DENN as it was found to be differentially expressed in normal and neoplastic cells. The DENN gene product is involved in MAP kinase signalling and GDP/GTP exchange. Downregulation of DENN expression results in marked apoptosis of cancer cells in vitro and in vivo.

The third novel human gene HUEL (SLC30A9) encodes a protein that exhibits nuclear-cytoplasmic shuttling, and is a member of the solute carrier superfamily and of the zinc transporter family. We have also isolated the novel human gene HALR (MLL3), which maps to chromosome 7q36 associated with leukaemia and developmental defects, and encodes a protein homologous to the ALR (ALL-1 related) gene product. The lab has characterized the novel human MOST-1 gene that exhibits tissue-specific expression, maps to chromosome 8q24.2, and is overexpressed/ amplified in high grade cancers of the breast and prostate. Genomics and proteomic strategies have been adopted for studying the “infectomics” of diseases related to enterovirus 71, dengue and SARS coronavirus.

The team has employed PCR and cycle sequencing for the molecular diagnosis and epidemiology of common and important human pathogens in Singapore, including dengue viruses, varicella-zoster virus, enterovirus 71, mumps virus, respiratory syncytial virus, human papillomaviruses, Neisseria gonorrhoeae and Chlamydia pneumoniae.

Yeo WM, Isegawa Y and Chow VT (2008) The U95 protein of human herpesvirus 6B interacts with human GRIM-19: silencing of U95 expression reduces viral load and abrogates loss of mitochondrial membrane potential. J. Virol. 82:1011-1020

Ho SY, Chua, SQ, Foo GWD, Locht C, Chow VT, Poh CL and Alonso S (2008) The highly attenuated Bordetella pertussis BPZE1 strain as a potential live vehicle for the delivery of heterologous vaccine candidates. Infect. Immun. 76:111-119

Jan ter Meulen, J, van den Brink EN, Poon LLM, Marissen WE, Leung CSW, Cox F, Cheung CY, Bakker AQ, Bogaards JA, Deventer EV, Preiser W, Doerr HW, Chow VT, Kruif JD, Peiris JSM and Goudsmit J (2006)  Human Monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Medicine. 3:e237

Surjit M, Liu B, Chow VT and Lal SK (2006) The nucleocapsid protein of severe acute respiratory syndrome-coronavirus inhibits the activity of cyclin-cyclin-dependent kinase complex and blocks S phase progression in mammalian cells. J. Biol. Chem. 281:10669-10681

Leong WF and Chow VT (2006) Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection. Cell. Microbiol. 8:565-580

Culiat, CT, Sakharkar KR, Sakharkar MK, Chow VT and Pervaiz S (2006) Functional and evolutionary analyses on expressed intronless genes in the mouse genome. FEBS Lett. 580:1472-1478

Koh WP, Chow VT, Phoon MC, Ramachandran N and Seow ALH (2005) Lack of association between chronic Chlamydophila pneumoniae infection and lung cancer among nonsmoking Chinese women in Singapore. Intl. J. Cancer. 114: 502-504

Surjit M, Kumar R, Mishra RN, Reddy MK, Chow VT and Lal SK (2005) The severe acute respiratory syndrome coronavirus nucleocapsid protein is phosphorylated and localizes in the cytoplasm by 14-3-3- mediated translocation. J. Virol. 79:11476-11486

Sakharkar KR and Chow VT (2004) Exploring genome architecture through GOV: a WWW-based gene order visualizer. Bioinformatics. 20, 6:984-985

Liew KJ and Chow VT (2004) Differential display RT-PCR analysis of ECV304 endothelial-like cells infected with dengue virus type 2 reveals messenger RNA expression profi les of multiple human genes involved in known and novel roles. J. Med. Virol. 72:597-609