publication scientifique internationale de haut "Impact factor" par un jeune chercheur (40 ans maximum)
Période de référence :
Dépôt des candidatures :
15 octobre 2016
Jérôme Moreaux a été récompensé pour son article RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma RECQ1 paru dans la revue Leukemia.
Multiple myeloma (MM) is a plasma cell cancer, characterized by the expansion of multiple myeloma cells (MMCs) in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the most downregulated genes. RecQ helicases are DNA unwinding enzymes involved in the maintenance of chromosome stability. Here we show that RECQ1 is significantly overexpressed in MMCs compared to normal plasma cells and that increased RECQ1 expression is associated with poor prognosis in three independent cohorts of patients. Interestingly, RECQ1 knockdown inhibits cells growth and induces apoptosis in MMCs. Moreover, RECQ1 depletion promotes the development of DNA double-strand breaks, as evidenced by the formation of 53BP1 foci and the phosphorylation of ataxia-telangiectasia mutated (ATM) and histone variant H2A.X (H2AX). In contrast, RECQ1 overexpression protects MMCs from melphalan and bortezomib cytotoxicity. RECQ1 interacts with PARP1 in MMCs exposed to treatment and RECQ1 depletion sensitizes MMCs to poly(ADP-ribose) polymerase (PARP) inhibitor. DNMT inhibitor treatment results in RECQ1 downregulation through miR-203 deregulation in MMC. Altogether, these data suggest that association of DNA damaging agents and/or PARP inhibitors with DNMT inhibitors may represent a therapeutic approach in patients with high RECQ1 expression associated with a poor prognosis.
"Our laboratory uses genome data, computing, mathematical modeling and unique cellular models to study hematological malignancies and their normal counterparts. These approaches work in tandem, with rapid technological advancements, to study tumorigenesis, understand the mechanisms of tumor progression and drug resistance to develop new ways to diagnose, treat and ultimately cure these cancers."
"Nature is dominated by chemically favoured processes. While biology is prone to evolution, universal principles of physical chemistry are not (at least not on the same time scale). It is my opinion that life has evolved mechanisms to circumvent undesired chemistry’’ -Raphaël Rodriguez-
Based on this thought, our laboratory has adopted ‘the small molecule approach’ to biology. We study cell biology at the molecular level using an integrated approach combining synthetic organic chemistry and molecular biology techniques. We custom design new probes and protocols to delineate mechanisms of action of small molecules. This includes cutting-edge small molecule imaging in cells by means of click chemistry, next generation sequencing and quantitative proteomics. During the course of our studies, these unbiased methods have previously led to the identification of novel therapeutic targets such as the lysine acetyl transferase NAT10 as a master regulator of aging, iron homeostasis has a druggable network in cancer stem cells and new anti-cancer strategies that consist of altering the chromatin landscape to control genome targeting with cisplatin drugs. The lab is currently focused on developing methods for personalized cancer treatments and elucidating roles of iron in cancer stem cell homeostasis. The group seeks to employ universal principles of physical chemistry and knowledge of biology to impact human medicine.
Professeur des Universités, Praticien Hospitalier, Ancienne Présidente de l'Université de Montpellier & Chargée de mission, Direction générale de la recherche et de l'innovation & Membre du Directoire de la Fondation Curie
Président du jury