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    Role of Rho GTPases in the immune system

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    Principal Investigator

    Jérôme Delon

     

    Objectives

    Analyse the role of small G proteins of the Rho family in T lymphocyte migration and activation.

     

    Group

    Meriem Khirat (M2 student)

    Héloïse Leroy (PhD student)

    Rachida Tacine (Technician, Paris Descartes University)

    Jérôme Delon (Inserm researcher)

     

    Questions addressed

    Our research theme focuses on the role of the Rho GTPases RhoA, Rac1 and Cdc42 in the physiology of immune cells, especially T lymphocytes.
    In this context, we study in particular the role of Fam65b and Fam49b which are atypical negative regulators of RhoA and Rac1 strongly expressed in T cells. These studies have already allowed us to reveal additional levels of regulation of Rho GTPases.
    In addition, we are also interested in the study of somatic mutations of Rho GTPases and their activators identified in cohorts of patients with various pathologies: immunodeficiencies, auto-inflammatory syndromes, and rare cutaneous diseases. Our work makes it possible to better understand the origin of these pathologies with the hope of proposing new therapeutic avenues.
    We address these topics using genetic, biochemical, cell biology and imaging techniques in cell lines, primary cells, and in KO mice models.

     

    Main publications

    Megrelis L, El Ghoul E, Moalli F, Versapuech M, Cassim S, Ruef N, Stein JV, Mangeney M and Delon J. (2018). Fam65b phosphorylation relieves tonic RhoA inhibition during T cell migration. Front Immunol. 9:2001.

    Froehlich J, Versapuech M, Megrelis L, Largeteau Q, Meunier S, Tanchot C, Bismuth G, Delon J and Mangeney M. (2016). FAM65B controls the proliferation of transformed and primary T cells. Oncotarget. 7: 63215-63225.

    Megrelis L and Delon J (2014). Rapid and robust analysis of cellular and molecular polarization induced by chemokine signaling. J Vis Exp (94).

    Rougerie P, Largeteau Q, Megrelis L, Carrette F, Lejeune T, Toffali L, Rossi B, Zeghouf M, Cherfils J, Constantin G, Laudanna C, Bismuth G, Mangeney M, Delon J. (2013). Fam65b is a new transcriptional target of FOXO1 that regulates RhoA signaling for T lymphocyte migration. J Immunol. 190(2):748-755.

    Rougerie P and Delon J. (2012). Rho GTPases: masters of T lymphocyte migration and activation. Immunol Lett. 142:1-13.

     

    Financial support:

               ANR

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