The major focus of my research has been on the application of replication-competent oncolytic herpes-simplex viruses (oHSV) for the treatment of prostate cancer. Oncolytic HSV-based vectors can replicate within and kill tumor cells (oncolysis), sparing normal cells. One major drawback is its limited capacity to spread intercellularly and kill neighboring cancer cells. To improve the clinical utility of oHSV-based therapies for prostate cancer, my ongoing studies have focused on the identification of chemotherapeutic agents and/or small molecule compounds that modulate important prostate cancer cell pathways and, when paired with appropriate oHSV vectors can increase oncolytic cancer cell destruction. I have pursued this line of research using two interrelated strategies: 1) Screened several FDA-approved chemotherapeutic agents in conjunction with oHSV to identify a synergistic combination that results augmented cell death both in vitro and in vivo. 2) Undertook an unbiased high-throughput chemical library screen to identify small molecule compounds that promote augmented oHSV spread in human prostate cancer cells. The coupling of oHSV virotherapy with small molecule discovery has allowed us to uncover novel pathways of viral oncolysis in prostate cancer and moreover, has led to increased efficacy in preclinical testing.