Professor of Medicine


Address:  

Shelby Building, Room 302
1825 University Boulevard
35294-2182

Telephone: (205) 975-7510 

Education

BS (Biology), Capital University of Medical Sciences, China, 1983 
MS (Immunology), Capital University of Medical Sciences, China, 1986
MD, Capital University of Medical Sciences, China, 1986

Research Description

Dr. Zhou's research centers on the characterization of apoptotic pathways with a view to therapeutic manipulation in cancer and autoimmune inflammatory disease. One of these approaches has been to develop monoclonal antibodies that target the proteins of the TNFR superfamily. Dr. Zhou has developed a novel agonistic monoclonal antibody, TRA-8, which exhibits a strong apoptosis-inducing activity in cancer cells without hepatocyte toxicity. The pre-clinical studies in various human cancer models demonstrate that TRA-8 might be a very promising anti-cancer agent regarding its efficacy and safety. The humanized version of TRA-8 has entered the Phase I trial. To support the future clinical development of anti-death receptor strategy, Dr. Zhou's focus has been on the intracellular control mechanisms of apoptosis resistance in cancer cells. Dr. Zhou's laboratory has recently identified a novel mechanism by which cancer cells developed resistance to death receptor-induced apoptosis. DDX3, a RNA helicase, functions as an adapter protein linking the death receptor and an apoptosis inhibitor at the death domain. This model might provide a novel therapeutic target for enhancement of death receptor-mediated apoptosis as well as a biomarker for predicting patients' response to TRA-8.    Dr. Zhou has collaborated closely with Dr. Mountz to develop a strategy to the utilization of  Fas ligand to eliminate autoimmune cells for treatment of human autoimmune diseases. Similar approaches are now being used to characterize the role of B lymphocyte stimulator (BLyS) in SLE in a coordinated effort involving collaboration with Dr. Kimberly. Dr. Zhou's another research focus is on the identification of novel serum biomarkers for early diagnosis of cancer. This involves in the development of a multiplex assay for potentially important cancer markers.   

Selected Publications

 
Shah N, Zhai G, Knowles JA, Stockard CR, Grizzle WE, Fineberg N, Zhou T, Zinn KR, Rosenthal EL, Kim H. 2011. (18)F-FDG PET/CT Imaging Detects Therapy Efficacy of Anti-EMMPRIN Antibody and Gemcitabine in Orthotopic Pancreatic Tumor Xenografts. Mol Imaging Biol. 2011 Apr 15. [Epub ahead of print] PMID: 21494920

Amm HM, Zhou T, Steg AD, Kuo H, Li Y, Buchsbaum DJ. 2011. Mechanisms of Drug Sensitization to TRA-8, an Agonistic Death Receptor 5 Antibody, Involve Modulation of the Intrinsic Apoptotic Pathway in Human Breast Cancer Cells. Mol Cancer Res. 9(4):403-17. PMID:21357440

Crowder RN, Zhao H, Chatham WW, Zhou T, Carter RH. 2011. B lymphocytes are resistant to death receptor 5-induced apoptosis. Clin Immunol. 139(1):21-31. PMID: 21276756

Sun M, Song L, Zhou T, Gillespie GY, Jope RS. 2011. The role of DDX3 in regulating Snail. Biochim Biophys Acta. 1813(3):438-47. PMID: 21237216 

Yokoi F, Yang G, Li J, Deandrade MP, Zhou T, Li Y. 2010. Earlier onset of motor deficits in mice with double mutations in Dyt1 and Sgce. J Biochem. 2010 Oct;148(4):459-66. PMID: 20627944

Frederick PJ, Kendrick JE, Straughn JM Jr, Della Manna DL, Oliver PG, Lin HY, Grizzle WE, Stockard CR, Alvarez RD, Zhou T, LoBuglio AF, Buchsbaum DJ. 2009. Effect of TRA-8 anti-death receptor 5 antibody in combination with chemotherapy in an ex vivo human ovarian cancer model. Int J Gynecol Cancer. 19(5):814-9. PMID: 19574765

Li X, Su K, Ji C, Szalai AJ, Wu J, Zhang Y, Zhou T, Kimberly RP, Edberg JC. 2008. Immune opsonins modulate BLyS/BAFF release in a receptor-specific fashion. J Immunol. 181(2):1012-8. PMID: 18606652

Oliver PG, LoBuglio AF, Zinn KR, Kim H, Nan L, Zhou T, Wang W, Buchsbaum DJ. 2008. Treatment of human colon cancer xenografts with TRA-8 anti-death receptor 5 antibody alone or in combination with CPT-11. Clin Cancer Res.14(7):2180-9. PMID: 18381960

Derosier LC, Vickers SM, Zinn KR, Huang Z, Wang W, Grizzle WE, Sellers J, Stockard CR Jr, Zhou T, Oliver PG, Arnoletti P, Lobuglio AF, Buchsbaum DJ. 2007. TRA-8 anti-DR5 monoclonal antibody and gemcitabine induce apoptosis and inhibit radiologically validated orthotopic pancreatic tumor growth. Mol Cancer Ther. 6(12 Pt 1):3198-207. PMID: 18089714

Estes JM, Oliver PG, Straughn JM Jr, Zhou T, Wang W, Grizzle WE, Alvarez RD, Stockard CR, LoBuglio AF, Buchsbaum DJ. 2007. Efficacy of anti-death receptor 5 (DR5) antibody (TRA-8) against primary human ovarian carcinoma using a novel ex vivo tissue slice model. Gynecol Oncol. 105(2):291-8. PMID: 17303227

Li Y, Wang H, Wang Z, Makhija S, Buchsbaum D, LoBuglio A, Kimberly R, Zhou T. 2006. Inducible resistance of tumor cells to tumor necrosis factor-related apoptosis-inducing ligand receptor 2-mediated apoptosis by generation of a blockade at the death domain function. Cancer Res. 66(17):8520-8. PMID: 16951164

Kaliberov SA, Chiz S, Kaliberova LN, Krendelchtchikova V, Della Manna D, Zhou T, Buchsbaum DJ. 2006. Combination of cytosine deaminase suicide gene expression with DR5 antibody treatment increases cancer cell cytotoxicity. Cancer Gene Ther. 13(2):203-14. PMID: 16082379