Heshan Sam Zhou, PhD
Research Program
Molecular Targets
Education Research and Professional Experience 1993-1995 1995-1998 1998-2002 2002-present Selected Awards and Professional Honors 1984 1987-1988 1991 1993 1995-1998 1998 Research Interest Publications O'Neal WK, Rose E, Zhou H, Langston C, Rice K, Carey D, Beaudet AL. Multiple advantages of alpha-fetoprotein as a marker for in vivo gene transfer. Mol Ther 2:640-648. 2000
B.S., Wuxi College of LI, Jiagsu, China, Microbiology, 1980
M.S., Hangzhou University, Zejiang, China, Biochemistry, 1982
Ph.D., University of Texas at Austin, Molecular Biology, 1993
Postdoc., Howard Hughes Medical Institute, Gene Therapy, 1995
Postdoctoral Research Associate, Howard Hughes Medical Institute, Baylor College of Medicine, Houston Texas
Cystic Fibrosis Foundation Postdoctoral Fellow, Dept of Mol & Human Genetics, Baylor College of Medicine, Houston Texas
Research Assistant Professor, Department of Molecular and Human Genetics, Shell Center for Gene Therapy, Baylor College of Medicine, Houston Texas
Assistant Professor (tenure track), Brown Cancer Center and Department of Medicine, University of Louisville, Louisville, KY
Excellent Staff Award, Jiangxi Academy of Sciences, Jiangxi, China
Visiting Scholarship, National Education Commission of China
Member Honor Society of Phi Kappa Phi
Excellent Ph.D. Dissertation, University of Texas at Austin
Postdoctoral Research Fellowship Grant (F984), North American Cystic Fibrosis Foundation
Member American Society of Gene Therapy
Dr. Zhou is interested in development of new adenoviral vectors and approaches for cancer gene therapies. Adenovirus deleted with the E1B55K gene is the world's first oncolytic virus approved for treatment for late-stage cancers. Adenovirus with deletion of E1B55K can selectively replicate in cancer cells and cause oncolysis. However, the mechanism of cancer selections remains poorly understood, and the efficacy of virus oncolytic replication that determines the therapeutic efficacy requires further improvement.
One of our current research projects is to study selective replication of E1B55K-deleted adenovirus in cancer cells. We investigate the functions of adenovirus E1B55K protein that are related to oncolytic replication. We have found that the E1B55K protein has a novel function involved in the induction of cell cycle-related genes, including cyclin E. E1B55K-induced cyclin E plays a critical role in viral replication. However, this E1B55K function is not essential for viral replication in cancer cells because cyclin E expression is frequently deregulated in cancer cells. Cyclin E overexpression or deregulation in cancer cells may be an important molecular basis for selected replication of E1B55K-deleted adenoviruses.
We are also active in development of viral vectors encoding therapeutic genes to improve systemic virotherapy; these genes may induce apoptosis and autophagy in cancer cells, or stimulate immune responses against tumor.
Finally, we are investigating the potential of food supplements in prevention of tumor recurrence after viral oncolytic treatments.
O'Neal WK, Zhou H, Morral N, Langston C, Parks RJ, Graham FL, Kochanek S, Beaudet AL. Toxicity associated with repeated administration of first-generation adenovirus vectors does not occur with a helper-dependent vector. Mol Med 6:179-95. 2000
Zhou H, Zou L, Ozol K, Pastore L, Shine D, Yang K. Stable transgene expression delivered by helper-dependent adenovirus vector in central nervous system. Molec Ther 2:105-113, 2000
Zhou H, Beaudet A. A new cell line with inducible E2a for production of higher titer and safer adenovirus vectors. Virology 275:348-357, 2000
Zou L, Yuan X, Zhou H, Yang K. Characterization of helper-dependent adenoviral vector-mediated gene transfer to aged rat brain. Human Gene Ther 12:181-191, 2001
Zhou H (Corresponding), Zhao T, Zhang W, Rao XM, Beaudet A. A cre expressing cell line and an E1/E2a double deleted helper virus for preparation of helper-dependent adenovirus vector. Mol Ther 3:613-622, 2001
Zou L, Yotnda P, Zhao T, Yuan X, Long Y, Zhou H, Yang K. Reduced inflammatory reactions to the inoculation of helper-dependent adenoviral vectors in traumatically injured rat brain. J Cereb Blood Flow Metab 20:959-970. 2002
Zhou H (Corresponding), Zhao T, Rao XM, Beaudet A. Production of helper-dependent adenovirus vector relies on helper virus structure and complementing. J Gene Medicine 4:498-509, 2002
Zhou H, Pastore L, Beaudet A. Helper-dependent adenovirus vector. Methods in Enzymology 346:177-198, 2002
Zhao T, Rao X, Li, L, Thompson T, McMasters K, Zhou H (Corresponding). Adenovirus with insertion-mutated E1a selectively propagates in liver cancer cells and destroys tumors in vivo. Cancer Res 63:3073-3078, 2003
Dong YB, Duncan B, Souza V, Zhou HS, McMasters KM. E2F-1 cancer gene therapy. Gene Ther Molec Biol 8:147-155, 2004
Rao X, Tseng MT, Zheng X, Dong Y, Jamshidi-Parsian A, Thompson TC, Brenner MK, McMasters KM, Zhou H (Corresponding author). E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells. Cancer Gene Ther 11:585-593, 2004
Jamshidi-Parsian A, Dong Y, Zhou H, McMasters KM. Gene expression profiling of E2F-1-induced apoptosis. Gene 344:67-77, 2005