Cytokines: Interferons and Chemokines
My research group studies the interactions of cytokines and chemokines with their receptors in normal and diseased cells and tissues. Through an understanding of how these biological response modifiers influence the innate and adaptive immune responses and directly exert their influence on non-immune target cells, we will be better positioned to develop therapeutic intervention strategies for a variety of clinical indications.
Our studies include identification of signal transduction pathways downstream of the interferon-alpha/beta receptor and the chemokine receptor, CCR5. We have extensively mapped signaling cascades that lead to both transcriptional and translational regulation, and assigned biological responses to specific cytokine- or chemokine- inducible signaling events, e.g. antiviral responses, growth inhibitory activities, chemotactic responses, proliferative responses.
We use immortalized human cell lines, gene deficient mice and patient specimens acquired from different human disease cohorts, for our in vitro and in vivo studies.
Broad Spectrum Antivirals
A major focus in the lab is the study of virus-host interactions in the context of developing broad spectrum antivirals. Through an examination of protein-protein interactions between ligands and receptors and between signaling effectors and viral intermediates, we are able to translate this information into antiviral drug development.
In 2003, studies were conducted to investigate the therapeutic potential of interferon-alpha in SARS patients during the Toronto outbreak. Encouraging results have directed our group's efforts towards examining interferon activity against a number of emerging infectious diseases, including avian influenza H5N1. Additionally, studies with poxviruses have revealed that activation of the chemokine receptor CCR5 is important for infection and ongoing studies are examining potential antiviral targets related to CCR5 antagonism.
Another focus of the group is investigating how dysregulation of cytokine and chemokine expression leads to pro-inflammatory events in various autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and lupus.
Director, Arthritis & Autoimmunity Research Centre
Professor, Department of Immunology, University of Toronto
Canada Research Chair in Women's Health & Immunobiology