Descrizione del progetto
Un angelo custode divenuto diabolico potrebbe rivelare bersagli terapeutici per molti tumori
Il cancro è vario e complesso, ma molti tumori mostrano alcune somiglianze. Le mutazioni nel gene TP53 che codifica per la proteina tumorale 53 (p53) sono più comunemente associate ai tumori nell’uomo. In qualità di «guardiano del genoma», la p53 regola la divisione cellulare e agisce da soppressore tumorale, impedendo alle cellule con DNA mutato o danneggiato di dividersi. Una mutazione TP53 altera inoltre il metabolismo cellulare, che a sua volta può indurre modifiche al DNA che controlla l’espressione genica (epigenetica), provocando un’espressione genica anomala che promuove ulteriormente lo sviluppo del cancro. MetEpiC sta approfondendo questo ciclo di interazioni per una più chiara comprensione dei percorsi con implicazioni per l'intervento terapeutico su diversi tipi di tumori.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
75654 Paris
Francia