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Faculty Detail     Name TONG ZHOU   Campus Address SHEL 302 Zip 2182 Phone 205-975-7510 E-mail tzhou@uab.edu Other websites

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Medicine  Med - Immunology/Rheumatology Professor Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor

Graduate Biomedical Sciences Affiliations Cellular and Molecular Biology Program  Medical Scientist Training Program

Research/Clinical Interest Title Specific Induction of Apoptosis in Autoimmune and Inflammatory Cells Description Dr. Zhou’s research is centered on the characterization of apoptotic pathways with a view to therapeutic manipulation in autoimmune and inflammatory disease. In the first approach, Drs. Zhou has collaborated closely with Dr. Mountz, to demonstrate that strategies centered on Fas ligand might prove useful in the therapeutic regulation of autoimmune disease. To by-pass the toxic effect of soluble Fas ligand, Dr. Zhou, in close collaboration with Dr. Mountz, has used cell-gene therapy consisting of an antigen presenting cell transfected with AdFas ligand to eliminate chronic inflammation and autoimmune disease in a number of murine models of these disease. The utility of this approach is being improved by the incorporation of elements that permit timed induction of discrete levels of Fas ligand to eliminate activated T cells in an antigen-specific manner. This APC-Fas L cell-gene therapy approach has proven useful in the experimental analysis of Fas-mediated apoptosis and antigen-induced cell death in autoimmune disease and may prove useful as a therapeutic strategy in the prevention of post-infectious chronic inflammation or organ-specific disease. In the second approach, Dr. Zhou has developed agonistic and antagonistic monoclonal antibodies that discriminate the DR5 TRAIL receptor and is using these to characterize the distribution of this receptor among T cell populations during activation responses as well as the associated signal transduction events. The ability of these monoclonal antibodies to specifically inhibit autoimmune reactions is being analyzed in various murine models, including models of SLE, collagen II-induced arthritis, and experimental allergic encephalitis. Similar approaches are now being used to characterize the role of B lymphocyte stimulator (BLyS) in SLE in a coordinated effort involving collaboration with Drs. Alarcon, Fessler, and Kimberly.

Selected Publications  Publication PUBMEDID Carter RH, Zhao H, Liu X, Pelletier M, Chatham W, Kimberly R, Zhou T. Expression and occupancy of BAFF-R on B cells in systemic lupus erythematosus. Arthritis Rheum 52:3943-3954, 2005    Straughn JM Jr, Oliver PG, Zhou T, Wang W, Alvarex RD, Grizzle WE, Buchsbaum DJ. Antitumor activity of TRA-8 anti-death receptor 6 (DR5) monoclonal antibody in combination with chemotherapy and radiation therapy in a cervical cancer model. Gynecol Oncol 101:46-54, 2005    Kaliberov SA, Chiz S, Kaliberova LN, Krendelchtchikova V, Della Manna D, Zhou T, Buchsbaum DJ. Combination of cytosine deaminase suicide gene expression with DR5 antibody treatment increases cancer cell toxicity. Cancer Gene Ther 13:203-214, 2006    Estes JM, Oliver PG, Straughn JM Jr, Zhou T, Wang W, Grizzle WE, Alvarez RD, Stockard CR, LoBuglio AF, Buchsbaum DJ. Efficacy of anti-death receptor 5 (DR5) antibody (TRA-8) against primary human ovarian carcinoma using a novel ex vivo tissue slice model. Gunecol Oncol 105:291-298, 2007    Zhou T, Fleck M, Mueller-Ladner U, Yang P, Wang Z, Gay S, Matsumoto S, Mountz JD: Kinetics of Fas-induced apoptosis in thymic organ culture. J Clin Immunol 17:74-84, 1997.    Zhou T, Song L, Yang P, Wang Z, Lui D, Jope RS: Bisindolylmaleimide VIII facilitates Fas-mediated apoptosis and inhibits T cell-mediated autoimmune diseases. Nature Medicine 5:42-8, 1999.    Zhang HG, Su X, Liu D, Liu W, Yang P, Wang Z, Edwards CK, Bluethmann H, Mountz JD, Zhou T: Induction of specific T cell tolerance by Fas ligand-expressing antigen-presenting cells. J Immunol 162:1423-30, 1999.

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