Integrative Structural & Chemical Biology

Drug discovery is an inherently inefficient process, particularly in oncology. The difficulty in matching the immense and complex chemical world with a desired physiological effect is illustrated by limitations such as harmful side effects and drug resistance, which defy the most powerful chemotherapeutics available.

Novel therapeutic targets and new ways to identify, to characterize and to develop anti-cancer drugs are needed. Most drug discovery efforts by pharmaceutical companies concern the development and / or expansion of their pre-clinical and clinical pipeline primarily targeting G protein-coupled receptors, nuclear receptors, ion channels and the active sites of enzymes (eg kinases).

Although this strategy is understandable for historical reasons and risk management, inhibitors of protein-protein interaction represents an alternative and almost unexplored reservoir for drug development in oncology. Thus, targeting protein-protein interaction interfaces appears a valuable and promising strategy, which is further underscored by an expected reduced occurrence of resistance that might arise due to mutations in the protein-protein interface.

In this context, our objectives are to identify, to understand, to validate and to target protein-protein interaction interfaces critically involved in tumor cell signaling, with the specific purpose of facilitating the transfer of therapeutic and pharmacological targets into preclinical and clinical development programs in oncology.

Laboratory Organisation

The team

From Left to Right: Etienne Rebuffet, Xavier Morelli, Yves Collette, Hélène Launay, Brigitt Raux, Elsa Drivet, Stéphane Betzi, Sébastien Combes, Iuliia Voitovich, Laurent Hoffer, Véronique Brechot, Karine Barral, Sabine Milhas, Philippe Roche, Carine Derviaux, Marie-Jeanne Basse, Mathias Vanhems.

Not in the picture: Jean-Michel Brunel, Fatiha Benmansour

About the team leaders

Xavier Morelli

Education

  • Since 2012 : Group Leader of the team iSCB, CRCM – Marseille, France
  • 2008-2012 : Group Leader of the team ID3, CNRS/IMR Laboratory – Marseille, France
  • since 2006 : Researcher CR1 CNRS section 21
  • 2002-2006 : Researcher CR2 CNRS section 21
  • 2000-2002 : Postdoctoral Fellow, Division of Thrombosis and Hemostasis, Harvard Medical School, Boston, USA (Supervisor : Bruce Furie)
  • 1996-1999 : PhD in Structural Biology, University of Paris XI, France

     

    Main achievements

    • French Pionneer in the discovery of Protein-Protein Interaction Inhibitors (research article published in PNAS in 2007)
    • Chemical databases dedicated to Protein-Protein Interactions
    • Co-founder of ZymGen, a startup in thrombosis in 2002.
    • National Secretary of the French Society of Chemoinformatics
    • Associate editor of the journal ‘BMC Pharmacology & Toxicology’
    • Member of the national scientific commitee of the ARC.

    Yves Collette

    Education

    • Since 2012 : Group Leader of the team iSCB, CRCM – Marseille, France
    • Since 2007: Director of the TrGET preclinical platform CRCM/IPC– Marseille, France
    • Since 2007 : Researcher DR2 INSERM
    • 2002-2007 : Researcher CR1 INSERM
    • 1998-2002 : Researcher CR2 INSERM
    • 1994-1997: European Community Postdoctoral Fellow, Immunity and Cancer Laboratory, INSERM U119, France (Supervisor : Pr Daniel Olive)
    • 1989-1994 : PhD in Virology, Free University of Brussel, Belgium (Supervisor : Pr Arsène Burny)

       

      Main achievements

      • Development of original chemical-biology approaches to discover, to study and to target pathological signaling
      • Co-discover of HIV-1 Nef Protein-Protein Interaction Inhibitors
      • Set up of a preclinical platform at Institut Paoli Calmettes
      • INSERM Contrat d’interface with Institut Paoli Calmettes (2008-2013)
      • Member of the national coordinated action 14.3 of the ANRS (2000-2007)
      • Member of the national scientific commitee of the ANRS (2005-2009)
      • Ex ante member of the Belgian national scientific commitee of the FNRS (2010-)