Research in my laboratory centers on the application of herpes simplex virus (HSV) vectors for cancer therapy and gene delivery to cells of the nervous system. Replication-competent oncolytic HSV vectors are being developed that target tumor cells for destruction, yet are non-pathogenic to normal tissue. The virus constructs are examined in various mouse tumor models (human xenografts, syngeneic implants (subcutaneous, intracranial, orthotopic) and transgenic mice) for efficacy and mechanism of action, their safety evaluated, and finally tested in clinical trials. A number of different vector strategies are being pursued: (i) viral gene mutations that are complemented by the cancer cell phenotype; (ii) transcriptionally targeted vectors using tumor cell-specific regulatory regions to drive ICP4 expression; and (iii) "armed" oncolytic vectors that express anti-cancer transgenes (immune-modulatory and anti-angiogenic). Current areas of interest include: immunotherapy using oncolytic HSV as 'in situ' cancer vaccines, oncolytic HSV-dendritic cell interactions, cancer stem-like (tumor-initiating) cells in tumors of the nervous system.