Chair, Department of Biochemistry and Biomedical Sciences
McMaster UniversityHamilton, Ontario Canada
The main focus of my research is virus pathogenesis. We study how the host responds to invading viruses along with strategies used by viruses to circumvent these responses. We have found that enveloped virus particles trigger a host response that culminates in induction of interferon responsive genes in the absence of interferon. This response relies on the cellular transcription factor IRF3. We have found that fusion at the cell membrane is sufficient to activate IRF3 and induce a cellular antiviral response. We are currently using screening assays to elucidate the pathways triggered following membrane fusion.
We are also studying strategies used by Herpes simplex virus type 1 (HSV-1) to counteract the cellular antiviral pathways initiated when HSV-1 enters into susceptible cells. We have found that the immediate early protein, ICP0, blocks activation and nuclear translocation of IRF3. The information extracted from these studies is being used to design therapeutic vectors for cancer therapy. For example, we have found that HSV-1 mutants that fail to express ICP0 preferentially replicate in and kill cancer cells that have lost responsiveness to interferon during tumorigenesis. The viruses, along with other related herpesviruses, are being developed as oncolytic viruses for cancer therapy.