Xiaoliu "Shaun" Zhang, PhD

Associate Professor Department of Pediatrics Section of Hematology-Oncology, Baylor College of Medicine

 

 

Contact Information:
xzhang@bcm.edu
713-798-1256

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Education:
MD. Tongji Medical University, Wuhan, China. 
PhD. The John Curtin School of Medical Research, Australian National University, Canberra, Australia

Research Interests:
The research interests in my laboratory are mainly focused in three areas. (1) Development of conditionally replicating herpes simplex virus (oncolytic HSV) for treatment of solid tumors, including breast cancer, prostate cancer, ovarian cancer, hepatocellular carcinoma and gliomas. Oncolytic viruses are genetically constructed in such a way that they can selectively replicate in tumor cells but not in normal cells. Unlike traditional gene-based forms of cancer therapy, oncolytic viruses kill tumor cells directly through their selective replication/cytolysis and consequent spreading to surrounding tumor tissues. These properties represent a major advantage over the inherent inefficiency of gene delivery and thus limited tumor cell killing by traditional gene therapy. Current oncolytic HSVs were exclusively constructed from type 1 virus (HSV-1). We recently constructed a novel oncolytic virus from HSV-2 that can selectively target tumor cells with an activated Ras signaling pathway. Designated FusOn-H2, it has multiple antitumor mechanisms, including the induction of cell membrane fusion (syncytia formation) and apoptosis in tumor cells, in addition to its direct cytolytic effects. Moreover, destruction of tumor cells by FusOn-H2 induces potent antitumor immune responses that further contribute to its overall antitumor effects. FusOn-H2 has subsequently shown potent antitumor activities in several tumor models. Currently FusOn-H2 is being manufactured in our center’s GMP facility for FDA requested toxicology studies and for phase I clinical trials. (2) Construction of HSV based vectors for gene transduction. We are developing both recombinant HSV vectors and HSV amplicons as a tool for gene delivery for gene therapy purpose. (3) Studies of HSV replication mechanisms. Our studies in this area are focused on configurational analysis of HSV DNA replicative intermediates and the accompanying homologous recombination mechanisms.

Selected Publications:
Zhang, X., Efstathiou, S. and Simmons A. (1994). Identification of novel herpes simplex virus replicative intermediates with field inversion gel electrophoresis: Implication for the viral DNA amplification strategies. Virology. 202: 530-539.

Wang H., Fu X. and Zhang X. (2001). Use of an uniquely designed HSV amplicon as a model to study viral replication mechanism. J. Virol. 75 (21): 10505-10510.

Fu X. and Zhang X. (2002). Potent Systemic Anti-tumor Activity from an Oncolytic Herpes Simplex Virus of Syncytial Phenotype. Cancer Res. 62(8): 2306-2312.

Fu, X. Wang, H. and Zhang X. (2002). High frequency of inter-molecule homologous recombination during HSV-mediated plasmid DNA replication. J. Virol. 76(12): 5866-5874.

Mikihito Nakamori, Xinping Fu, Raphael Rousseau, Si-Yi Chen and Xiaoliu Zhang (2004). Destruction of nonimmunogenic mammary tumor cells by a fusogenic oncolytic herpes simplex virus induces potent antitumor immunity. Mol. Ther. 9(5): 658-665.

Fu X, L. Tao and X. Zhang (2003). The promoter of the strictly late viral gene UL38 is a tumor specific in the context of an oncolytic herpes simplex virus. Gene Ther. 10(17): 1458-1464.
Nakamori, M. Fu, X. Meng, F. Jin, A. Bast, R. and X. Zhang (2003). Enhanced therapy of metastatic ovarian cancer with a double fusion oncolytic herpes simplex virus. Clin. Cancer Res. 9(7): 2727-2733.

Fu X, Tao L, Prigge J, Cai R, Zhang X. (2006). A mutant type 2 herpes simplex virus deleted for the protein kinase domain of the ICP10 gene is a potent oncolytic virus. Mol. Ther. 13(5): 882-890.

Xinping Fu, Lihua Tao, Min L, William E. Fisher and Xiaoliu Zhang (2006) Effective treatment of pancreatic cancer xenografts with a conditionally replicating virus derived from type 2 herpes simplex virus. Clin. Cancer Res. 12(10): 3152-3157.

Hongtao Li, Aurelie Dutuor, Lihua Tao, Xinping Fu and Xiaoliu Zhang (2007). Virotherapy with an HSV-2-derived oncolytic virus induces potent antitumor immunity against neuroblastoma. 2006. Clin. Cancer Res. 13(1): 316-322.

Hongtao Li, Aurelie Dutuor, Xinping Fu and Xiaoliu Zhang (2007). Induction of strong antitumor immunity by an HSV-2-based oncolytic virus in a murine mammary tumor model. Journal of Gene Medicine. 9(3): 161-169.

©2002, Cell And Gene Therapy, Baylor College of Medicine
One Baylor Plaza, N1002, Houston, TX 77030, (713)798-1246
URL: http://www.bcm.edu/genetherapy Email:cagt@bcm.edu
(Modified:August 15, 2006- SM)