Centre de Référence Maladies Rares

U1035 INSERM

Biotherapy of genetic diseases, inflammatory disorders and cancer (BMGIC)

FR: Biologie Fondamentale Appliquée à la Médecine

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miRCaDe team (MicroRNAs in Cancer and Development)

Christophe GROSSET
INSERM Research Director, head of MiRCaDe team

Martin HAGEDORN
Assist. Prof., co-head of MiRCaDe team

Discover our projects:

The miRCaDe team studies the post-transcriptional regulation of genes by microRNAs in adult and pediatric cancers of brain, liver and pancreas, as well as in embryonic development (see Figure). Some of our projects are focused on two genes, Glypican-3 (GPC3) and beta-catenin (CTNNB1), that control Wnt signaling, normal cell gene reprogramming and embryonic tissue development. These two genes play an important role in both hepatocellular carcinoma (HCC), a frequent and aggressive cancer of the liver in adults, and hepatoblastoma (HBL), a rare cancer of the liver that mainly affect children under 5-year of age. Using innovative experimental tools (FunREG method, (1) ; Dual Fluorescence-FunREG screening system, (2)), we identify microRNAs (miRNA) regulating Glypican-3 and beta-catenin in tumoral hepatic cells and uncover potent antitumoral candidates for miRNA-replacement therapy in liver cancer. Other projects are focused on the preclinical and molecular study of pediatric brain tumors, especially diffuse intrinsic pontine gliomas (DIPG). Using the BH3-profiling system (3) and the chick chorioallantoic membrane as a model system (4, 5), we aim at modeling and transcriptionally exploring experimental tumors, including those that derivate from patients’ tumoral cells, and at participating in the development of new treatments and a more personalized medicine. The developmental part of the projects uses Xenopus embryo as a model system (6, 7). We study the role of microRNAs and genes during development with a particular focus on liver and pancreas organogenesis and cancer-related signaling pathways, such as Wnt and Hippo. Xenopus embryos have been shown to express highly evolutionary conserved miRNAs during development and their functions can be unraveled through an easy knock-down strategy (8). Because of its numerous advantages and the easiness with which chemical screening can be performed in embryos, Xenopus constitutes the ultimate animal model to add fundamental scientific advances in our understanding of the role of miRNAs in cancer-associated post-transcriptional deregulations.

INSERM U1035! - University of Bordeaux
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sarah.lesjean@inserm.fr