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    Exploiting cancer genetic vulnerabilities identified using genome-wide CRISPR-Cas9 screens for therapeutic intervention

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    SÉMINAIRE DE L'INSTITUT COCHIN

    Stéphane Angers 

    Stéphane Angers

    Faculty of Pharmacy & Department of Biochemistry,
    University of Toronto, Canada

     

    Mercredi 26 avril 2017 à 12h30

     

     invité par Mark Scott

     

    Institut Cochin, 22 rue Méchain, 75014 Paris
    Salle de conférence Rosalind Franklin, 2e étage

    Our laboratory has developed genome-wide CRISPR-Cas9 functional screening approaches to probe the genetic wiring of cancer cells. This work has led to the identification of “core” fitness genes required for the growth of all cell types and of “context-specific” fitness genes required specifically for a limited number of cancer types. Our work in pancreatic cancers revealed the Wnt receptor FZD5 as one such “context-specific” fitness gene for which we have developed a monoclonal antibody exhibiting tumour growth inhibition. We are also performing CRISPR-Cas9 chemogenomic screens to identify mechanism of drug resistance and to identify genes that provide hypersensitivity to standard of care therapeutic agents. Our unpublished work on glioblastoma will be discussed.

    Selected publications:

    • Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors. Steinhart Z, Pavlovic Z, Chandrashekhar M, Hart T, Wang X, Zhang X, Robitaille M, Brown KR, Jaksani S, Overmeer R, Boj SF, Adams J, Pan J, Clevers H, Sidhu S, Moffat J, Angers S. Nat Med. 2017 Jan;23(1):60-68.
    • PRICKLE1 Contributes to Cancer Cell Dissemination through Its Interaction with mTORC2. Daulat AM, Bertucci F, Audebert S, Sergé A, Finetti P, Josselin E, Castellano R, Birnbaum D, Angers S, Borg JP. Dev Cell. 2016 May 23;37(4):311-25.
    • Identification of Novel Smoothened Ligands Using Structure-Based Docking. Lacroix C, Fish I, Torosyan H, Parathaman P, Irwin JJ, Shoichet BK, Angers S. PLoS One. 2016 Aug 4;11(8):e0160365.
    • SAPCD2 Controls Spindle Orientation and Asymmetric Divisions by Negatively Regulating the Gαi-LGN-NuMA Ternary Complex. Chiu CW, Monat C, Robitaille M, Lacomme M, Daulat AM, Macleod G, McNeill H, Cayouette M, Angers S. Dev Cell. 2016 Jan 11;36(1):50-62.
    • High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities. Hart T, Chandrashekhar M, Aregger M, Steinhart Z, Brown KR, MacLeod G, Mis M, Zimmermann M, Fradet-Turcotte A, Sun S, Mero P, Dirks P, Sidhu S, Roth FP, Rissland OS, Durocher D, Angers S, Moffat J. Cell. 2015 Dec 3;163(6):1515-26.

     

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