个人简介

Fonds de la Recherche en Sante du Quebec post-doctoral fellow, 2005-2008 Heart and Stroke Foundation of Canada graduate fellow, 2001-2004 Fonds de la Recherche en Sante du Quebec graduate fellow, 2001-2003 Canadian Hypertension Society grad

研究领域

Biochemistry/""Metabolism/Signaling/and Regulation""/Bioanalytical/Chemical Biology

Signalling pathways and molecular mechanisms controlling directed cell migration. Our research focuses on the signal transduction pathways and molecular mechanisms controlling directed cell migration, or chemotaxis, in eukaryotic cells. Chemotaxis is central to many biological processes, including the embryonic development, wound healing, the migration of white blood cells (leukocytes) to sites of inflammation or bacterial infection, as well as the metastasis of cancer cells. Cells can sense chemical gradients that are as shallow as a 2% difference in concentration across the cell, and migrate towards the source of the signal, the chemoattractant. This is achieved through an intricate network of intracellular signaling pathways that are triggered by the chemoattractant signal. These pathways ultimately translate the detected chemoattractant gradient into changes in the cytoskeleton that lead to cell polarization and forward movement. In addition, many cells such as leukocytes and Dictyostelium, transmit the chemoattractant signal to other cells by themselves secreting chemoattractants, which increases the number of cells reaching the chemoattractant source. We are particularly interested in understanding the role and regulation of the evolutionarily conserved Target of Rapamycin Complex 2 (TORC2) during chemotaxis. TORC2 controls chemotaxis in leukocytes and Dictyostelium, and has been linked to cancer cell metastasis. TORC2 is central to chemotaxis, acting as an integrator of multiple upstream signals to coordinate the complex cellular response to chemoattractants.

近期论文

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K. Sumita, H. Yoshino, M. Sasaki, N. Majd, E.R. Kahoud, H. Takahashi, K. Takeuchi, T. Kuroda, S. Lee, P.G. Charest, K. Takeda, J.M. Asara, R.A. Firtel, D. Anastasiou, and A.T. Sasaki. Degradation of Activated K-Ras Orthologue via K-Ras Specific Lysine Residues is Required for Cytokinesis. J Biol Chem. 289:3950-9 (2014). V. Kölsch, Z. Shen, S. Lee, K. Plak, P. Lotfi, J. Chang, P.G. Charest, J.L. Romero, T.J. Jeon, A. Kortholt, S.P. Briggs, and R.A. Firtel. Daydreamer, a Ras effector and GSK-3 substrate, is important for directional sensing and cell motility. Mol. Biol. Cell. 24:100-14 (2013). K. Takeda, D. Shao, M. Adler, P.G. Charest, W.F. Loomis, H. Levine, A. Groisman, W.J. Rappel, and R.A. Firtel. Incoherent feedforward control governs adaptation of activated Ras in eukaryotic chemotaxis pathway. Sci. Signal. 5, ra2 (2012). I. Hecht, M.L. Skoge, P.G. Charest, E. Ben-Jacob, R.A. Firtel, W.F. Loomis, H. Levine, and W.J. Rappel. Activated membrane patches guide chemotactic cell motility. PLoS Comput. Biol. 7(6):e1002044 (2011). P.G. Charest, Z. Shen, A. Lakoduk, A.T. Sasaki, S.P. Briggs and R.A. Firtel. A Ras signaling complex controls the RasC-TORC2 pathway and directed cell migration. Dev. Cell. 18:737-49 (2010). P.G. Charest and R.A. Firtel. "TORCing" neutrophil chemotaxis. Dev. Cell 19(6):795-6 (2010). S. Zhang*, P.G. Charest*, and R.A. Firtel. Spatio-temporal Regulation of Ras Activity Provides Directional Sensing. Curr. Biol. 18(20):1587-93 (2008). * Equal authorship. V. Kölsch, P.G. Charest and R.A. Firtel. The regulation of cell motility and chemotaxis by phospholipid signaling. J. Cell Sci. 121(Pt 5):551-9 (2008). P.G. Charest and R.A. Firtel. Big roles for small GTPases in the control of directed cell movement. Biochem. J. 401(2):377-90 (2007). F.F. Hamdan, M.D. Rochdi, B. Breton, D. Fessart, D.E. Michaud, P.G. Charest, S.A. Laporte and M. Bouvier. Unraveling g protein-coupled receptor endocytosis pathways using real-time monitoring of agonist-promoted interaction between beta-arrestins and AP-2. J. Biol. Chem. 282(40):29089-100 (2007). A.T. Sasaki, C. Janetopoulos, S. Lee, P.G. Charest, K. Takeda, L.W. Sunddheimer, R. Meili, P.N. Devreotes and R.A. Firtel. G Protein-Independent Ras/PI3K/F-Actin Circuit Regulates Basic Cell Motility. J. Cell. Biol. 178(2):185-91 (2007). P.G. Charest, G. Oligny-Longpré, H. Bonin, M. Azzi and M. Bouvier. The V2 vasopressin receptor stimulates ERK1/2 activity independently of heterotrimeric G protein signalling. Cell. Signal. 19(1):32-41 (2007).