My laboratory studies the virus: host interaction at the molecular level. We are particularly interested in vesicular stomatitis virus (VSV) and the human coronaviruses. We are studying the ways in which the host cell responds to viral infection and the ways in which these viruses counter this response and how they use host cell pathways to enable their own propagation.
VSV is a relatively simple animal virus possessing only five genes. We are using this virus as a tool to better understand how cells respond to being infected. While I was in Dr. John Bell’s laboratory in Ottawa we discovered that many tumour cells have defects in their ability to respond to viral infection and this makes them very susceptible to infection and killing by this virus. There is mounting evidence that in the course of becoming malignant, cancer cells need to shed or alter functions that are used by normal cells to respond to viral infection. We are continuing to study this defective response in multiple myeloma cells. Multiple myeloma is a malignancy of mature B cells or plasma cells that arises in the bone marrow. The prognosis for this form of cancer continues to be dismal and there is a strong need for novel therapeutics. Our preliminary data indicates that these malignant cells may be particularly attractive targets for oncolytic viral therapy when we begin clinical trials with VSV.
My laboratory is also studying the interaction between the matrix protein of VSV and the mitochondria of infected cells. We recently discovered this interaction and are working to determine the role that this plays in the virus: host interaction. While many (most) viruses express proteins that regulate mitochondrial function in order to determine when and if the host cell dies following infection, such a function had not yet been identified in the genome of VSV. We are investigating the apoptotic response of the host cell to viral infection and the role that the matrix protein has in regulating this response.
Coronaviruses have attracted attention following the recent SARS epidemic. However, this group of viruses causes a variety of diseases that are important to both human and veterinary medicine. My laboratory is studying the “group-specific” genes found in the genomes of human coronaviruses. These small genes are not required for the replication of these viruses in cultured cells but appear to play an important role in determining pathogenesis in the host animal, however the precise function of these genes is not yet determined. We are studying the impact that these viral proteins have on the innate response of human cells to infection.