Michel Bouvier, an expert in the field of signals transduction through G-protein-coupled receptors (GPCRs), did postdoctoral training in molecular pharmacology in the lab of R.J. Lefkowitz at Duke University. In his research Bouvier aims to understand, at the molecular level, the mechanisms controlling GPCR signalling selectivity and efficacy. His work has led to paradigm shifts, including the discovery of inverse agonism at GPCRs and of 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.
Bouvier 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 revealed 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.
Julius Axelrod Award in Pharmacology, 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, 2001–12
Beautrait, A. et al. “A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling.” Nat Commun 8 (2017): 15054.
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 (2016): 907–19. *co-corresponding author
Paradis, J.S. et al. “Receptor sequestration in response to βarrestin-2 phosphorylation by ERK1/2 governs steady-state levels of GPCR cell-surface expression.” Proc Natl Acad Sci USA. 112, no. 37 (2015): E5160–E5168.
Audet, M., and M. Bouvier. “Restructuring G-Protein-Coupled Receptor Activation.” Cell 151, no. 1 (2012): 14–23.
Galés, C. et al. “Probing the activation-promoted structural rearrangements in pre-assembled receptor-G protein complexes.” Nat. Struct. Mol. Biol. (2006): 778–86.