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Thème de recherche

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Epigenetics defines when and where genes are expressed. Epigenetic marks are reversible and inheritable, integrate the impact of the environment and provide cellular plasticity. Aberrant epigenetic patterns are involved in tumor formation, maintenance and resistance. DNA methylation and epigenetic modifications, in general, are reversible and can be modulated by chemical agents. It is in this context that we develop an interdisciplinary approach aiming at the development of new inhibitors of DNA methylation to modulate gene expression and, more recently, of new inhibitors of histone methyltransferases. Our interdisciplinary approach combines Medicinal Chemistry, Pharmacology, Molecular Biology, Biophysics, Chemical Biology and Cellular Biology.

We have successfully used several chemical strategies (rational drug design, pharmacomodulation, chemical library screening) and set upbiological assays to characterize the cellular consequences induced by these inhibitors in cancer cells. Our findings encouraged us about the role of DNA methylation in tumor aggressiveness and the ability of epigenetic drugs to reprogram cancer cells (liste des publications).

Lately, we started touse as novel chemical tools for the understanding of the molecular mechanisms underlying the aberrant methylation in cancer cells and target them.

A precise elucidation of why the methylation processes is aberrant in cancer is the key to a better understanding of the disease and to fight it. The understanding of these processes will open the way to the discovery of novel anti-cancer targets, eventually also biomarkers, and innovative therapeutic strategies.

Figure DNA methylation and cancer. In cancers, together with a global DNA hypomethylation of the genome that participates to genomic instability, an hypermethylation of the promoter of certain genes is observed leading to their silencing. The demethylation of the promoters by inhibitors of DNA methyltransferases (DNMTi) should restore tumor suppressor gene expression and reprogram the cancer cells. The red lollipops represent methylated CpG sites, while white lollipops represent demethylated CpG sites.