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> Stages de M2 > Liste des stages proposés pour l’année 2015-2016 > Molecular mechanisms of growth control from mouse models to human (...)

Molecular mechanisms of growth control from mouse models to human disease.

proposé par Gana PANASYUK, INSERM U1151/CNRS UMR 8253, Necker Enfants Malades Institute (INEM), 14 Rue Maria Helena Vieira da Silva, CS61431, 75993 Paris cedex 14

Projet de stage : The M2 training will be conducted in frame of the project which aims to uncover the molecular mechanisms of growth control in mammals relevant to human pathology. Growth, or biomass accumulation, is a fundamental property of living organism. It is achieved by the coordination of catabolic and anabolic metabolism. The evolutionary conserved Phosphoinositide 3-Kinase/mammalian Target Of Rapamycin (PI3K/mTOR) signalling pathway is essential for growth control and its activity is commonly deregulated in human pathologies. Highly prevalent nowadays diabetes and obesity are independent risk factors for a number of malignancies with the highest correlation for liver cancer. We have recently shown that the alteration of insulin and nutrient signalling transduction elements involved in the metabolic syndrome provides cell autonomous growth advantage to hepatocytes leading to tumorigenesis. We discovered that activated Akt2 Ser/Thr kinase, a downstream effector in PI3K/mTOR pathway, is sufficient to provide metabolic adaptations to drive liver cancer. In our further work we identified a transcription factor which belongs to the nuclear hormone receptor family - peroxisome proliferator-activated receptor gamma (PPARγ), as a key factor for liver tumorigenesis downstream of activated Akt2. Our study uncovered an unappreciated role of PPARγ in pathological liver growth and suggested that it could represent a potential therapeutic target in liver cancer. The successful candidate will be trained in highly dynamic scientifically stimulating international English-French bilingual environment. The expertise of the team is reflected in the publication track record and is recognised by the highest national evaluation and the financial support of several foundations.

Techniques mises en œuvre par le stagiaire : The proposed M2 training will focus on the molecular mechanisms of PPARγ activation and regulation downstream of activated Akt2. During the training student will be exposed to numerous techniques and experimental approaches including the mouse models of human diseases ; gene therapy using viral vectors ; therapeutic pharmacological approaches ; signal transduction and proteomic approaches.

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