PRIMARY FACULTY

ChouZen Giam, Ph.D.
Professor
Microbiology & Immunology
 
4301 Jones Bridge Road
Bethesda MD 20814
Office: 301-295-9624
Fax: 301-295-1996
cgiam@usuhs.mil

The research in my lab focuses on the molecular biology and pathogenesis of three human cancer viruses: human T-lymphotropic virus type 1 (HTLV-1), Kaposi sarcoma-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV-8), and hepatitis C virus (HCV). We are particularly interested in how regulatory proteins of these viruses usurp cellular mRNA transcriptional machineries, cell cycle control mechanisms, and signal transduction pathways to facilitate viral replication. We have a long standing interest in the mechanisms of action of the HTLV-1 transactivator/oncoprotein, Tax, and its role in the etiology of adult T-cell leukemia. We have shown recently that Tax can activate an E3 ubiquitin ligase, the anaphase promoting complex (APC), ahead of schedule. This activity of Tax causes premature degradation of many critical mitotic and cell cycle regulators during S phase, leading to DNA aneuploidy and cellular senescence. Currently, we are actively studying the relationship between unscheduled APC activation by Tax and cellular senescence. We have also been studying the structures and functions of two regulatory proteins, K-Rta and K-bZIP of KSHV/HHV-8, with a special emphasis on their roles in viral replication and latency reactivation. Finally, a study to investigate the mechanism of hepatitis C virus (HCV) replication has been initiated in 2003. We are using proteomic approaches to identify cellular factors important for HCV replication.

Selected Publications

Fu, D., Kuo Y-L., Jeang, K-T., and Giam, C-Z. Human T-lymphotropic Virus Type I Transactivator Tax activates I-kB Kinase by Inhibiting I-kB Kinase g Subunit-Associated Serine/Threonine Protein Phosphatase 2A. J Biol Chem 2003; 278(3):1487-93
 
Liao W., Tang Y., Lin S-F., Kung H-J., and Giam C-Z., K-bZIP of Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus type 8 (KSHV/HHV-8) Binds KSHV/HHV-8 Rta and Represses Rta-Mediated Trans-activation. J Virol. 2003; 77(6):3809-15.
 
Liu, B., Liang, M., Kuo, Y-L, Liao, W., Boros, I., Kleinberger, T., Blancato, J., and Giam, C-Z Human T-Lymphotropic Virus Type 1 Oncoprotein Tax Promotes Unscheduled Degradation of Pds1p/Securin and Clb2p/Cyclin B1 and Causes Chromosomal Instability. Mol Cell Biol. 2003; 23(15):5269-5281.
 
Liao, W., Liao W., Tang Y., Xu C-J., and Giam C-Z., KSHV/HHV-8 Transcriptional Activator, Rta, is an Oligomeric DNA-binding Protein That Interacts with Tandem Arrays of Phased A/T-Trinucleotide Motifs. J Virol. 2003; 77(17):9399-411.

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