Accredited Professor
 |
Contact InformationDépartment de génétique médicale |
.T 514 345-4931, poste 6900 |
ThemesThe group’s research focuses on the biochemical and cell-based characterization of medically relevant enzymes to uncover the molecular basis of their mechanisms of action, specificities and regulation. We also aim to identify compounds that modulate enzyme activities. This knowledge can provide insight into the precise physiological role of these enzymes, and contribute to the design of potential therapeutic agents. Application of enzyme kinetic techniques to study the molecular basis of the mechanism and specificity of enzymes; structure-function relationships; study of enzyme-inhibitor interactions with the aim of designing new or improved inhibitors of therapeutic importance; modification of enzymes to alter their structural and/or functional properties (stability, specificity, catalytic mechanism); design of experimental protocols in enzyme kinetics; assay development for high-throughput-screening of compound libraries and for functional studies. Deubiquitinating Enzymes The modification of cellular proteins by ubiquitin and ubiquitin-like proteins is an essential regulatory mechanism in many biological processes. The isopeptide bond between ubiquitin and a protein, or between ubiquitin molecules in a polyubiquitin chain, can be cleaved by deubiquitinating enzymes. The human genome encodes approximately 95 deubiquitinating enzymes, mot of them being cysteine proteases, which are relatively poorly characterized. Our group uses detailed biochemical characterization and cell-based studies to provide insights into the molecular mechanisms and physiological roles of these enzymes, in order to elaborate novel molecular therapeutic strategies based on interference with deubiquitinating events. Enzymes from Clostridium difficile Studies are being carried out to characterize at the molecular level cysteine proteases from the bacteria Clostridium difficile, an important human pathogen. In the search for alternative antibiotics for treating bacterial infections, we are also evaluating how these enzymes influence the virulence of Clostridium difficile infections. Other cysteine proteases It was demonstrated that a viral papain-like cysteine protease (PLpro) from the Severe Acute Respiratory Syndrome (SARS) coronavirus, previously known to be involved in processing a viral polyprotein precursor and to contribute to the virus replicative cycle, also possesses deubiquitinating activity. This discovery raised provocative hypotheses regarding the ability of the SARS virus to evade cellular defense mechanisms. Our group has also made many important contributions to the study of cathepsin mechanisms, catalysis, specificity and regulation. In addition to general intracellular protein degradation and turnover within the endosomal/lysosomal system, cathepsins (mammalian cysteine proteases) can fulfill specific functions and also play an important role in a variety of pathological processes such as degenerative diseases and malignant tumour development. |