Institut de recherche biomédicale
    Vous êtes ici : Accueil / L'Institut / Séminaires / Causes and consequences of metabolic deficiency induced by mutations in splicing factors

    Causes and consequences of metabolic deficiency induced by mutations in splicing factors

    Webinaire de l'Institut Cochin

    Jeudi 21 janvier 2021 - 12h00 - Pour obtenir le lien d'accès par visioconférence, envoyez un mail à


    Kevin Rouault-Pierre

    Centre for Haemato-Oncology, Barts Cancer Institute - Cancer Research UK, London, UK


     invité par Diana Passaro



     Our work focuses on studying integration of stresses (e.g. mutations, microenvironment feedback) in normal and malignant human haematopoietic stem cells, in order to understand and prevent the transition from pre-malignant stage to overt cancer.

    Prevention and early detection of malignant transformation are key in the fight against cancer. Early stages of disease initiation comprise the acquisition of founder mutations that involve frequent aberration in the epigenetic and splicing machinery. The core spliceosomal factor mutated in cancers, include SF3B1, which leads to mis-splicing events and altered gene regulation in many solid and blood cancers including uveal melanoma, breast cancers, bladder cancers, acute myeloid leukaemia, myelodysplastic syndromes (MDS) and chronic lymphoid leukaemia.

    The high incidence of splicing mutations in MDS, >50% of patients, makes it an ideal surrogate model to study mis-splicing events’ impact on cancer. Mice models of SF3B1mut have failed to recapitulate the main mis-splicing events identified in human, due to human and mice sequence discrepancies. Using human primary models that we previously developed and published, we have identified mis-splicing events in the heme and serine biosynthesis pathways that create a vulnerability in MDS cells which we propose to exploit to target and eliminate cancer cells at the different stages of the disease, from pre-malignancy to overt cancer transformation.


    Quelques publications