Xiaoliu “Shaun” Zhang M.D. Ph.D.

The research interests in my laboratory are mainly in the following three areas:

1) Development of conditionally replicating herpes simplex virus (oncolytic HSV) for treatment of solid tumors. In particular, we have recently created a new class of oncolytic HSV – fusogenic oncolytic HSV, which destroys tumors by a unique mechanism medicated by direct cytolysis of virus replication and syncytial formation of cell membrane fusion. This new class of oncolytic virus has shown a significantly enhanced antitumor effect over the first generation oncolytic HSV on several tumor models including breast cancer, ovarian cancer, prostate cancer, liver cancer and brain tumor. Further work is being conducted to elucidate the interplay between the oncolytic effect of the virus and body’s antiviral and antitumor immunity.

2) Development of herpes simplex virus derived vectors for gene delivery. We are especially interested in constructing HSV amplicon vectors, which are a non-toxic, high capacity, and multiple gene delivery system. We have made some crucial improvements on the design of amplicon vector and its helper virus, and are now using this vector system to deliver genes into central nervous system and other organs for gene therapy purposes.

3) Studies of HSV replication mechanism. We have demonstrated that amplicon and its helper virus share striking similarities in their replication patterns and mechanisms, such as the occurrence of frequent intermolecular homologous recombination. We have now developed a unique amplicon construct, which mimics HSV genome, for studying HSV replication mechanism. As HSV amplicon construct is much simpler than HSV genome and is therefore easier to manipulate, this amplicon system should be very useful for further exploration of HSV replication mechanisms.

Shaun's Gene Therapy Web Site

Recent Publications (PubMed)

Wang, H, Fu, X, Ma, C, and X. Zhang (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 X. Zhang (2001). Systemic delivery of herpes simplex virus vectors mediated by liposome formulation. Mol. Ther. 4 (5): 447-453.

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

Xinping Fu, Lihua Tao, Aiwu Jin, Richard Vile, Malcolm K. Brenner,
and Xiaoliu Zhang (2003). Expression of a Fusogenic Membrane Glycoprotein by an
Oncolytic Herpes Simplex Virus Potentiates the Viral Antitumor Effect. Mol. Ther. 7(6): 748-754.

Nakamori M, Fu X, Meng F, Jin A, Tao L, Bast R. C Jr, Zhang X (2003). Effective therapy of metastatic ovarian cancer with an oncolytic herpes simplex virus incorporating two membrane fusion mechanisms. Clin. Cancer Res. 9(7): 2727-33.