Description du projet
Un ange gardien corrompu pourrait révéler des cibles thérapeutiques pour de nombreux cancers
Le cancer est une maladie diverse et complexe, mais la plupart des cancers présentent certaines similitudes. Les mutations du gène TP53 portant le code de la protéine tumorale 53 (p53) sont le plus souvent associées à des cancers humains. En tant que «gardienne du génome», la p53 régule la division cellulaire et agit comme suppresseur de tumeur, empêchant la division des cellules à l’ADN endommagé ou muté. En outre, la mutation de la TP53 modifie le métabolisme cellulaire, ce qui peut provoquer des modifications de l’ADN contrôlant l’expression génétique (épigénétique), se traduisant par une expression génétique anormale qui favorise le développement du cancer. MetEpiC étudie ce cycle d’interactions pour mieux comprendre les voies ayant des implications pour le ciblage thérapeutique de plusieurs types de cancers.
Objectif
Carcinogenesis is a multi-factorial disease which combines genetic mutations, aberrant epigenetic landscape and altered cell metabolism. TP53 which is the most mutated gene in human cancers, is known to regulate cell metabolism. It has been recently established that the metabolic status of cells can modulate the epigenetic landscape. The goal of this proposal is to characterize metabolic-driven modulation of epigenetic landscape during carcinogenesis using TP53 mutated cancers as models. In this project, we plan to address how TP53 mutations alter cell metabolism and the epigenome, thus creating abnormal gene expression facilitating carcinogenesis. Thanks to our preliminary data we will focus our attention on Acetyl-CoA metabolism and histone acetylations. This project will take advantage of state-of-the art approaches such as metabolomics, epigenomics and transcriptomics. My expertise on epigenetics and metabolism, as well as the expertise of the supervisor in the field of TP53 and carcinogenesis, are major assets for this project. Altogether, we expect that unraveling novel mechanisms interconnecting TP53 mutations, cellular metabolism and epigenome will provide new insights for understanding cancer development. Moreover, we expect to propose innovative strategies to tackle cancers harboring mutated TP53 thanks to combination of drugs targeting metabolism and the epigenome. This fellowship will definitively help me to conduct a unique and promising research line in the European Community with the final goal to establish myself as an independent scientist.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
75654 Paris
France