Detection of extracellular RNA
Extracellular or circulating nucleic acids derived from infected or damaged cells can be of virus or self origin. Once recognized and taken up by healthy cells, these nucleic acids rapidly and potently lead to the production of cytokines, including interferon. While interferon is important to protect against infections and cancer, inappropriate interferon responses lead to a variety of diseases, including autoimmunity. While class A scavenger receptors (SRAs) are required for binding and internalization of circulating nucleic acids, little is known about how individual SRA family members carry out these functions. Surprisingly, little is also understood about the cellular trafficking or localization of different nucleic acid species following uptake by SRAs. We have uncovered several unexplained anomalies in how different forms and lengths of nucleic acids traffic within cells and induce interferon following uptake by SRAs. We are continuing work to study the internalization, trafficking and signaling of various forms and lengths of nucleic acids to understand the mechanisms of how they activate cytokines such as interferon. Given that interferon can either prevent disease or cause disease, depending on its regulation, understanding basic mechanisms of interferon production in response to circulating nucleic acids is of critical importance.
IRF3-mediated innate immune responses
Cells respond to virus infection by inducing a set of proteins that function to block virus replication and spread. We have discovered that in response to all enveloped viruses, cells can recognize the general entry process, following disruption of the cell membrane. We identified an essential cellular factor, IRF3, that is activated and induces a non-specific anti-viral response that protects the cell against diverse viruses, by targeting conserved viral processes. IRF3 is emerging as a key player in recognizing and responding to many types of cellular stress, suggesting that entry of virus particles is likely sensed as a host stress response. Our studies explore how the virus entry process activates this stress response. Findings from this project will enable the development of novel, generic antiviral therapies capable of protecting against new, emerging viruses. Moreover, as IRF3 is implicated in a myriad of seemingly unrelated diseases, understanding its activation and function is of clinical importance.
Discovering and developing oncolytic therapies
We design viruses for anti-cancer therapies. We are currently developing a herpesvirus strain to selectively Immunotherapy, harvesting the power of the immune system to target cancer, is emerging as a potentially powerful therapeutic approach. Some tumors, which are considered "immune hot" tumors, are effectively targeted by current immunotherapy approaches such as checkpoint blockade immunotherapy. However, "immune cold" tumors require pre-treatment with therapies that induce an immune response within the tumor prior to treatment with checkpoint blockade immunotherapy. Oncolytic viruses are emerging as novel therapies that specifically target cancer cells and not healthy cells, and induce potent immune responses. Our laboratory focuses on herpesvirus-based oncolytic viruses, and studies signaling pathways, mechanisms of oncolytic activity and generation of therapeutic combination therapies. tumour cells. We also study downstream functional effects of oncolytic therapy and combination treatments using in vitro and in vivo models.
Virus-host interactions in bats
75% of emerging diseases have an animal origin. SARS caused a global pandemic in 2003 and we lost about forty individuals in Canada. Bats are speculated to be reservoirs of SARS coronavirus and several viruses of zoonotic potential. However, bats themselves do not display clinical signs of disease. Our research project aimed at understanding virus-host interactions in a natural wildlife reservoir will enable us to develop novel treatment strategies for other mammals, including humans.