CHUM Research Centre
Department of medicine, Université de Montréal
Programmes de biologie moléculaire et sciences biomédicales, Université de Montréal
514 890-8000, ext. 25119 (office) - ext. 28910 (lab)
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Canadian Arthritis Network
OsteoArthritis Research Society International
American Society for Biochemistry and Molecular Biology
Osteoarthritis, inflammation, cartilage, cytokines, prostaglandins, molecular biology, chromatin, epigenetics, polymorphisms, animal experimentation.
Our studies are aimed at defining the mechanisms involved in the onset, duration and resolution of inflammatory and catabolic events in articular joint tissues, with the ultimate goal of identifying novel molecular targets for the treatment or prevention of osteoarthritis. Current laboratory projects include:
Role of PPARgamma in osteoarthritis:
PPARgamma is a ligand-activated transcription factor belonging to the nuclear receptor superfamily and plays important roles in the regulation of several cellular processes. We have shown that PPARgamma activators downregulated the expression of several genes considered essential in the pathogenesis of osteoarthritis and were protective in animal models of the disease.
Our laboratory is further characterizing the role of PPARgamma in osteoarthritis with a particular emphasis on the mechansims that regulate PPARgamma expression. Additional studies are aimed at understanding the exact molecular mechanisms by which PPARgamma activation modulates gene expression. Elucidating these issues will improve our understanding of the role of PPARgamma in osteoarthritis and will be helpful in the developpement of new therapeutic strategies.
Expression and function of mPGES-1 in articular tissues:
mPGES-1 catalyzes the terminal step in the biosynthesis of PGE2, which plays critical roles in the pathogenesis of osteoarthritis. Studies from our laboratory and others indicate that inhibition of mPGES-1 is a promising therapeutic target in osteoarthritis. Our objective is to characterize the molecular mechanisms involved in the regulation of mPGES-1 gene expression, with a particular emphasis on the role of epigenetic modifications.
Genetic studies in osteoarthritis:
Although the etiology and the molecular aspects of the pathogenesis of osteoarthritis are unknown, epidemiological and genetic studies have demonstrated that genetic factors are strong determinants of osteoarthritis. Therefore, identifying genes that may be involved in osteoarthritis is a promising approach to understand the molecular basis and pathogenesis of the disease. We are studying the role of genetic variation in a number of candidate genes. Our goal is to identify functionally significant genetic variations that play a role in the susceptibility to and/or severity of osteoarthritis.