Descripción del proyecto
Un ángel guardián transformado en diablillo podría revelar las dianas terapéuticas de muchos tipos de cáncer
El cáncer es una enfermedad diversa y compleja, pero muchos tipos de cáncer presentan ciertas similitudes. Las mutaciones en el gen TP53 que codifica la proteína 53 (p53) se asocian habitualmente con el cáncer en seres humanos. En tanto que «guardián del genoma», la p53 regula la división celular y actúa como supresor de tumores deteniendo la división de las células con un ADN mutado o dañado. Además, la mutación del TP53 altera el metabolismo celular, que a su vez puede provocar modificaciones en el ADN que controla la expresión génica (epigenética), lo que resulta en una expresión génica anormal que promueve aún más el desarrollo del cáncer. MetEpiC está investigando este ciclo de interacciones para obtener una mayor comprensión de las rutas e implicaciones para centrarse desde el punto de vista terapéutico en varios tipos de cáncer.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
75654 Paris
Francia