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G protein-coupled receptor • molecular pharmacology • cell imaging • cardiovascular diseases • pre-term birth.
My research focuses on understanding the molecular and cellular mechanisms regulating G protein-coupled receptors (GPCRs), a class of membrane receptor that is involved in many physiological responses, and is the target of more than 30% of marked drugs. We are interested in the development of novel molecules with allosteric, biased signaling modes of action, in particular for the prostanglandin PG2α (FP) receptor, which will redirect signaling responses in cells. Using innovative imaging and biophysical approaches, we also study the dynamics of protein complexes involved in receptor trafficking and signaling for different GPCRs, in particular for the angiotensin II type 1. My laboratory is involved in developing novel fluorescently tagged biosensors for studying GPCR signaling and trafficking in live cells, with the goal of identifying small molecules that regulate these processes. Our research program aims to provide new insights into the molecular details of GPCR signaling and trafficking, with the goal of identifying new means to improve hormone and drug efficacy, especially in cardiovascular diseases, inflammation, pre-term birth and cancer.
Functional selectivity profiling of the angiotensin II type 1 receptor using pathway-wide BRET signaling sensors. Namkung Y, LeGouill C, Kumar S, Cao Y, Teixeira LB, Lukasheva V, Giubilaro J, Simões SC, Longpré JM, Devost D, Hébert TE, Piñeyro G, Leduc R, Costa-Neto CM, Bouvier M, Laporte SA. Sci Signal. 2018 Dec 4;11(559). pii: eaat1631. doi: 10.1126/scisignal.aat1631. PMID: 30514808.
Manifold roles of β-arrestins in GPCR signaling elucidated with siRNA and CRISPR/Cas9. Luttrell LM, Wang J, Plouffe B, Smith JS, Yamani L, Kaur S, Jean-Charles PY, Gauthier C, Lee MH, Pani B, Kim J, Ahn S, Rajagopal S, Reiter E, Bouvier M, Shenoy SK, Laporte SA, Rockman HA, Lefkowitz RJ. Sci Signal. 2018 Sep 25;11(549). pii: eaat7650. doi: 10.1126/scisignal.aat7650. PMID: 30254056.
A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling. Beautrait A, Paradis JS, Zimmerman B, Giubilaro J, Nikolajev L, Armando S, Kobayashi H, Yamani L, Namkung Y, Heydenreich FM, Khoury E, Audet M, Roux PP, Veprintsev DB, Laporte SA, Bouvier M. Nat Commun. 2017 Apr 18;8:15054. doi: 10.1038/ncomms15054. PMID: 28416805.
Monitoring G protein-coupled receptor and β-arrestin trafficking in live cells using enhanced bystander BRET. Namkung Y, Le Gouill C, Lukashova V, Kobayashi H, Hogue M, Khoury E, Song M, Bouvier M, Laporte SA. Nat Commun. 2016 Jul 11;7:12178. doi: 10.1038/ncomms12178. PMID: 27397672.
The conformational signature of β-arrestin2 predicts its trafficking and signalling functions. Lee MH, Appleton KM, Strungs EG, Kwon JY, Morinelli TA, Peterson YK, Laporte SA, Luttrell LM. Nature. 2016 Mar 31;531(7596):665-8. doi: 10.1038/nature17154. PMID: 27007854.