Research
Epigenetic Regulation and Cancer : E. Julien

The structure of chromatin and its epigenetic modifications play a crucial role in cellular identity, and their alterations are key factors in cancer development. The main objective of our research team is to investigate the epigenetic signaling pathways regulated by KMT5 family methyltransferases, which catalyze the methylation of lysine 20 on the N-terminal tail of histone H4. To achieve this, we employ cutting-edge genomic and proteomic approaches, using prostate cancer as our primary model. Our research focuses on three main areas: (i) the functions of KMT5 family methyltransferases in oncogenic processes; (ii) the identification and characterization of the non-histone substrates of these enzymes; and (iii) the identification and study of new synthetic lethality models induced by the combination of chemical inhibitors targeting epigenetic enzymes and conventional anticancer agents. This approach aims to overcome the challenges posed by resistance and side effects of standard therapies by identifying novel therapeutic combinations with potentially greater potency.

Axis 1: The functions of KMT5 family methyltransferases in oncogenic mechanisms
We have undertaken the study of gene networks regulated by the catalytic and non-catalytic activities of enzymes from the KMT5 family (SET8, SUV4-20H1, and SUV4-20H2), with the goal of characterizing the underlying molecular mechanisms. Our objective is to better understand the role of these enzymes in prostate cancer, particularly in the progression towards metastatic stages and hormone therapy resistance.

Axis 2: Identification and characterization of non-histone substrates of these enzymes
Focusing on the SET8 enzyme, we have initiated the characterization of new signaling pathways mediated by the methylation of non-histone proteins within chromatin. We aim to determine how SET8-mediated methylation of these proteins influences genome stability and cell cycle regulation under normal and cellular stress conditions.

Axis 3: Discovery and characterization of new synthetic lethalities associated with epigenetic drugs
Chromatin structure modifications, unlike genetic alterations, are reversible and thus represent a promising therapeutic target. This property opens up new possibilities in cancer treatment, especially through the development of epi-drugs: molecules capable of targeting key factors in epigenetic mechanisms. The goal of this third research axis, carried out in collaboration with chemistry teams, is to discover new compounds targeting these mechanisms and explore their synergy with existing anti-cancer agents.


© Institut de Recherche en Cancérologie de Montpellier - 2011 - Tous droits réservés - Mentions légales - Connexion - Conception : ID Alizés