Heshan Sam Zhou, PhD


Assistant Professor, Department of Surgery; Associate Scientist, James Graham Brown Cancer Center

Research Program
Molecular Targets

Education
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

Research and Professional Experience

1993-1995
Postdoctoral Research Associate, Howard Hughes Medical Institute, Baylor College of Medicine, Houston Texas

1995-1998
Cystic Fibrosis Foundation Postdoctoral Fellow, Dept of Mol & Human Genetics, Baylor College of Medicine, Houston Texas

1998-2002
Research Assistant Professor, Department of Molecular and Human Genetics, Shell Center for Gene Therapy, Baylor College of Medicine, Houston Texas

2002-present
Assistant Professor (tenure track), Brown Cancer Center and Department of Medicine, University of Louisville, Louisville, KY

Selected Awards and Professional Honors

1984
Excellent Staff Award, Jiangxi Academy of Sciences, Jiangxi, China

1987-1988
Visiting Scholarship, National Education Commission of China

1991
Member Honor Society of Phi Kappa Phi

1993
Excellent Ph.D. Dissertation, University of Texas at Austin

1995-1998
Postdoctoral Research Fellowship Grant (F984), North American Cystic Fibrosis Foundation

1998
Member American Society of Gene Therapy

2004
Member American Association for Cancer Research

Research Interest
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. 

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

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

Contact Information

CTR Building
505 South Hancock Street
Louisville, KY 40202
(502) 852-5745