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Michel Bouvier Molecular Pharmacology

Michel Bouvier is an expert in the field of signals transduction through G protein-coupled receptors (GPCRs). His research program aims at understanding at the molecular level the mechanisms controlling GPCR signalling selectivity and efficacy.  His work led to paradigm shifts including the discovery of inverse agonism at GPCRs and pharmacological chaperones to restore folding of disease-causing genetically mutated GPCRs. His work on the functional selectivity of GPCRs contributed to establishing the concept of ligand-biased signalling. He also pioneered the use of bioluminescence resonance energy transfer (BRET) for the study of protein-protein interactions and signalling activity in living cells. In addition to the development of screening assays that are now used for drug discovery, this methodology allowed to reveal the oligomeric nature of GPCRs and the role of higher order protein complexes in the spatio-temporal regulation of signal transduction under normal and pathological conditions. These tools and new concepts provide the foundation to elucidate how the macromolecular architecture and arrangement of signalling molecules provide the selectivity and fidelity to assure the appropriate propagation of information in cells.

Awards

Julius Axelrod award in Pharmacology of the American Society of Pharmacology and Experimental Therapeutics, 2017.

Fellow of the Academy of Science of the Royal Society of Canada, 2014.

Senior Investigator Award from the Canadian Society for Molecular Biosciences, 2012.

Fellow, Canadian Academy of Health Sciences, 2006.

Canada Research Chair in Signal Transduction and Molecular Pharmacology, 2001-2022.

Relevant Publications

Beautrait, A., Armando, S., Zimmerman, B., Stallaert, W., Audet, M., Laporte, S.A. and Bouvier, M.: Specific inhibition of arrestin/AP-2 by a newly identified chemical probe. [Nature Communication in press]

Thomsen, A.R.B., Plouffe, B., Cahill III, T.J., Shukla, A.K., Tarrasch, J.T., Dosey, A.M., Kahsai, A.W., Strachan, R.T., Pani, B., Mahoney, J.P., Huang, L., Breton, B., Heydenreich, F.M., Sunahara, R.K., Skiniotis, G., Bouvier, M.*, Lefkowitz, R.J.*: Biophysical Basis for Sustained G Protein Signaling by Internalized G Protein-Coupled Receptors. Cell 11; 166: 907-19, 2016. *co-corresponding author

Paradis, J.S., Ly, S., Blondel-Tepaz, É., Galan J.A., Beautrait, A., Scott M.G., Enslen H., Marullo, S., Roux P.P. and Bouvier M.: Receptor sequestration in response to -arrestin-2 phosphorylation by ERK1/2 governs steady-state levels of GPCR cell-surface expression. Proc Natl Acad Sci USA., 112(37):E5160-8, 2015.

Audet, M. and Bouvier, M.: Restructuring G-Protein-Coupled Receptor Activation. Cell, 151(1):14-23, 2012.

Galés, C., Van Durm, J.J., Schaak, S., Pontier, S., Percherancier, Y., Audet, M., Paris, H. and Bouvier, M: Probing the activation-promoted structural rearrangements in pre-assembled receptor-G protein complexes. Nat. Struct. Mol. Biol., 13:778-786, 2006.

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Appointment

Senior Fellow Molecular Architecture of Life

Institution

Université de MontréalDepartment of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer

Education

PhD (Neurological Sciences) Université de Montréal

BSc (Biochemistry) Univerité de Montréal

Postdoctoral training, Molecular Pharmacology in the laboratory of R.J. Lefkowitz Duke University Medical Center

Country

Canada

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