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College of Graduate Studies student abstract So the university community can learn more about research College of Graduate Studies students conduct in their pursuit of an MUSC degree, The Catalyst publishes their dissertation abstracts in this column. Each published abstract represents a successful defense of a student’s research as judged by the college faculty. Dissertation Title: Novel transcriptional regulation strategies for targeting gene therapy vectors for the treatment of prostate cancer. Student: Jan Woraratanadharm, Department of Microbiology and Immunology. Mentor: Jian-yun Dong, M.D., Ph.D., professor, Dept of Microbiology and Immunology. Future Plans: Working for local biotech company in Mt. Pleasant: Genphar Inc.   Prostate cancer is currently the second leading cause of cancer death in American men. Currently available treatment options are often ineffective in the locally advanced stages. Thus, there is a great need for new treatments in order to improve outcomes.  One such strategy is to specifically eliminate prostate cancer cells through the expression of cytotoxic genes specifically in prostate cancer cells using a recombinant adenovirus (Ad) vector. In order to eliminate prostate cancer cells through the expression of Fas ligand, our lab previously developed a complex Ad vector expressing a Fas ligand green fluorescent protein (FasL-GFP) fusion protein under the control of the Tet-regulatory system. This Ad vector was unique in that both hCMVie-regulated tTA expression and TRE-regulated FasL-GFP expression were incorporated into a single complex vector known as Ad/FasL-GFP.    In addition, the Ad/FasL-GFP vector demonstrated efficient killing of several cancer cell types including prostate cancer cells. Although the activity of this vector on prostate cancer cells was quite effective, if this vector is to be used in the human setting, it is imperative to restrict its toxic effects to only prostate cancer cells.  However, the majority of currently available expression regulation systems express only modest levels of cytotoxic proteins in target cells, or lack sufficient cell type specificity to be considered safe.    To address this issue, we have constructed two novel complex Ad vector regulation systems, known as the positive feedback loop with prostate specificity (PFLPS) and differentially suppressible tetracycline regulated expression system (DiSTRES) regulation systems. These two regulation systems greatly enhanced GFP reporter expression in prostate cancer cells, while maintaining tight control of expression in non-prostate cancer cells.  These two novel transcriptional regulation systems have broad applications for use as components of toxic vectors in order to express sufficient concentrations of toxic proteins in cancer cells, or alternatively, could be manipulated to regulate essential genes in a highly efficient conditionally replicative adenovirus (CRAd) specifically directed to prostate cancer cells.    The PFLPS and DiSTRES regulation systems serve as two promising new approaches in the development of both specific and effective vectors for cancer gene therapy.     Friday, Sept. 15, 2005 Catalyst Online is published weekly, updated as needed and improved from time to time by the MUSC Office of Public Relations for the faculty, employees and students of the Medical University of South Carolina. Catalyst Online editor, Kim Draughn, can be reached at 792-4107 or by email, catalyst@musc.edu. Editorial copy can be submitted to Catalyst Online and to The Catalyst in print by fax, 792-6723, or by email to petersnd@musc.edu or catalyst@musc.edu. To place an ad in The Catalyst hardcopy, call Community Press at 849-1778.