Chou-Zen Giam

Ph.D.

Department of Primary Appointment:
School of Medicine
Microbiology and Immunology
Title
Professor
Location: Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
The molecular biology and pathogenesis of human retroviruses and viral oncogenesis. How chronic NF-kB activation promotes genomic instability and cellular senescence.
Email
chou-zen.giam@usuhs.edu
Office Phone
(301) 295-9624
Department Website
Microbiology and Immunology

Education

B.S. Chemistry, National Taiwan University, Taipei, Taiwan (05/1975)
Ph. D. Molecular Biology and Biochemistry, University of Connecticut Health Center, Farmington, CT, USA (05/1983)
Post-doctoral Fellow, Laboratory of Molecular Virology, NCI, NIH, Bethesda, MD, USA (09/1987)

Biography

The work in my lab revolves around human viruses, with a special emphasis on human T-cell leukemia virus type 1 (HTLV-1), and with occasional forays into other viruses such as HIV and KSHV. We seek a mechanistic understanding of how viral regulatory proteins hijack cellular mediators of mRNA transcription, cell cycle control, and signal transduction to effect viral replication and pathogenesis, especially, oncogenesis. My interest in cancer viruses and human retroviruses developed initially in the early 1980s in the Laboratory of Molecular Virology (LMV) at the NIH where I was a post-doctoral fellow under the direction of Dr. George Khoury. Our major focus at that time was to understand how transcriptional enhancer elements drive eukaryotic mRNA synthesis by studying the HTLV-1 trans-activator, Tax, and its interaction with the cellular transcription machinery. After leaving LMV for the academia, I have been continuously funded by grants from the NIH and other funding agencies (AmFAR, VA, and DoD). We (and others) have since elucidated the mechanism by which Tax activates viral transcription and contributed to current understanding of how HTLV-1 infects, replicates and causes diseases. Due to the global nature of HTLV-1 infection, we frequently collaborate with colleagues in continental US, Asia (Japan, Taiwan, Hong Kong), Europe (France, UK, Germany, Italy, etc.), Africa (Uganda), and South America (Brazil). Together with our domestic and international partners, we seek fundamental understanding of HTLV-1 replication, persistence, and pathogenesis, and strive to translate basic science findings into preventive measures and therapeutic approaches for HTLV-1-associated diseases, especially adult T cell leukemia (ATL). Our current efforts focus on (1) elucidating the mechanisms that underlie the genomic instability of ATL cells; (2) understanding how the transcriptional activity of NF-B drives the induction of cellular senescence; (3) identifying the genetic alterations in ATL cells that facilitate the clonal expansion of HTLV-1-infected T cells based on whole genome sequence information; and (4) uncovering the mechanisms that regulate HTLV-1 latency and reactivation.

Representative Bibliography

Biosketch Link
Biosketch:

NF-kB signaling mechanisms in HTLV-1-induced adult T-cell leukemia/lymphoma. Harhaj EW, Giam CZ, FEBS J. 2018. doi: 10.1111/febs.14492.

HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma-A Tale of Two Proteins: Tax and HBZ. Giam CZ, Semmes OJ. Viruses. 2016 Jun 16;8(6). pii: E161. https://www.ncbi.nlm.nih.gov/pubmed/27322308

HTLV-1 Tax Stimulates Ubiquitin E3 Ligase, Ring Finger Protein 8, to Assemble Lysine 63-Linked Polyubiquitin Chains for TAK1 and IKK Activation. Ho YK, Zhi H, Bowlin T, Dorjbal B, Philip S, Zahoor MA, Shih HM, Semmes OJ, Schaefer B, Glover JN, Giam CZ. PLoS Pathog. 2015 Aug 18;11(8):e1005102. https://www.ncbi.nlm.nih.gov/pubmed/26285145

KSHV vCyclin counters the senescence/G1 arrest response triggered by NF-kB hyperactivation. Zhi H, Zahoor MA, Shudofsky AM, Giam CZ. Oncogene. 2015; 34(4):496-505. NIHMSID: NIHMS550287 https://www.ncbi.nlm.nih.gov/pubmed/24469036

HTLV-1 tax-induced rapid senescence is driven by the transcriptional activity of NF-kB and depends on chronically activated IKKa and p65/RelA. Ho YK, Zhi H, DeBiaso D, Philip S, Shih HM, Giam CZ. Journal of Virology. 2012; 86(17):9474-83. https://www.ncbi.nlm.nih.gov/pubmed/22740410

Complex cell cycle abnormalities caused by human T-lymphotropic virus type 1 Tax. Yang L, Kotomura N, Ho YK, Zhi H, Bixler S, Schell MJ, Giam CZ. Journal of Virology. 2011; 85(6):3001-9.

NF-kB hyper-activation by HTLV-1 tax induces cellular senescence, but can be alleviated by the viral anti-sense protein HBZ. Zhi H, Yang L, Kuo YL, Ho YK, Shih HM, Giam CZ. PLoS pathogens. 2011; 7(4):e1002025. https://www.ncbi.nlm.nih.gov/pubmed/21552325

Activation of the anaphase promoting complex by HTLV-1 tax leads to senescence. Kuo YL, Giam CZ. The EMBO journal. 2006; 25(8):1741-52. https://www.ncbi.nlm.nih.gov/pubmed/16601696

Published video: https://www.youtube.com/watch?v=votp2hRndIk&spfreload=10

Published video: https://www.youtube.com/watch?v=XasVBcMRGls&spfreload=10