Equipe d’Accueil : « Génomique fonctionnelle des tumeurs solides  » (FunGeST)

Intitulé de l’Unité : Centre de Recherche des Cordeliers – Inserm UMRS.1138

Nom du Responsable de l’Unité : Jessica Zucman-Rossi

Nom du Responsable de l’Équipe : Jessica Zucman-Rossi

Adresse :  Centre de Recherche des Cordeliers – 15 rue de l’école de médecine – 75006 Paris

Responsable de l’encadrement : : Didier Jean

Tél : 06.73.32.16.01    E-mail:  didier.jean@inserm.fr

Résumé du projet 

Pleural mesothelioma (PM) is a rare cancer that originates from the neoplastic transformation of mesothelial cells of the pleura. PM is also classified as an occupational disease since asbestos is the major risk factor for the occurrence of this cancer. Despite the discontinuation of the use of asbestos in Western countries (ban in 1997 for France), PM remains a major public health problem. Up to now, PM is globally an incurable cancer and there is a strong need to develop new therapies.  To find relevant strategies to PM treatment, a better understanding of PM biology is needed and the biological diversity of these tumors must be taken into account.

The M2 project will focus on the characterization of intra-tumor heterogeneity and the identification of genes and signal pathways discriminant according to the histologic and molecular phenotype of PM. The main objective is to elaborate new therapeutic strategies taking account both inter- and intra-tumor heterogeneity. This project relies in our biological resource collections, consisting of PM primary cell lines and of frozen and FFPE tumors samples. The methodological approaches include bulk and single-cell genomic analysis, spatial transcriptomic, and functional analysis of cancer cells using methods in molecular and cellular biology. This research involves several steps from the isolation and characterization of tumor cell subpopulations, genetic alteration and gene expression profiling, assessment of gene and pathway activities to the gene modulation using pharmacological, RNA interference and gene editing strategies. The results will provide new knowledge about PM pathogenesis. In this context of a highly aggressive cancer with no effective therapy, the project aims to lead to the implementation of a precision medicine for PM. The M2 student will be supervised by a researcher and an engineer. He will benefit from our extensive biobanks of tumor samples, the strong interconnection with the clinical services taking care of PM patients, and the expertise of the entire team in bioinformatics and tumor genomics.

Ce projet s’inscrit dans la perspective d’une thèse

Type de financement prévu : Contrat doctoral (école doctorale) ou Ligue contre le Cancer

Ecole Doctorale de rattachement :  HOB  « Hématologie – Oncogenèse – Biothérapies »

 

Dernières Publications en lien avec le projet :

  1. Assié J.-B., Meiller C., Stern E., Lasvergnas J., Arnould M., Pan L., Montagne F., Sequeiros R., Al Zreibi C., Del Nery E., Genovesio A., Lantuejoul S., Le Pimpec Barthes F., Zucman-Rossi J., Jaurand M.-C., Blanquart C., Wald O. and Jean D. Pharmacogenomic characterisation of a large collection of patient-derived cell lines identifies novel therapeutic options for pleural mesothelioma. Cancer Research., in revision.
  2. Paternot S., Raspé E., Meiller C., Tarabichi M., Assié J., Libert F., Remmelink M., Bisteau X., Pauwels P., Blum Y., Le Stang N., Tabone‐Eglinger S., Galateau‐Sallé F., Blanquart C., Van Meerbeeck J.P., Berghmans T., Jean D. and Roger P.P. Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4 /6 inhibition. Molecular Oncology. 2024, 18: 866–894.
  3. Meiller C., Montagne F., Hirsch T.Z., Caruso S., de Wolf J., Bayard Q., Assié J.-B., Meunier L., Blum Y., Quetel L., Gibault L., Pintilie E., Badoual C., Humez S., Galateau-Sallé F., Copin M.-C., Letouzé E., Scherpereel A., Zucman-Rossi J., Le Pimpec-Barthes F., Jaurand M.-C. and Jean D. Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma. Genome Med. 2021, 13: 113.
  4. Blum Y., Meiller C., Quetel L., Elarouci N., Ayadi M., Tashtanbaeva D., Armenoult L., Montagne F., Tranchant R., Renier A., de Koning L., Copin M.-C., Hofman P., Hofman V., Porte H., Le Pimpec-Barthes F., Zucman-Rossi J., Jaurand M.-C., de Reyniès A. and Jean D. Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications. Nat Commun. 2019, 10: 1333.