Composition

• 49 researchers, engineers, technicians
• 7 post-doc, 17 PhD students, 7 M2 students

  Facilities

• Cell Imaging Platform PRIMACEN and Proteomics Platform PTP
• Animal facility
• Electrophysiology coupled to calcium imaging
• High throughput quantitative PCR
• L2 sector for human cell culture and retroviral transduction
• DNA sequencing core facility

  Activity

The central theme of the four research groups of the INSERM U982 within IRIB is devoted to neuronal and neuroendocrine differenciation and communication. Several pathologies of the central nervous system (neurodegenerative diseases, lissencephaly, brain tumors) and the neuro-endocrine system (obesity, neuroendocrine tumors) are associated to abnormalities in cell differentiation, migration, survival and intercommunication. The research project of our Unit aims to contribute to the elucidation of the cellular and molecular mechanisms of neuronal and neuroendocrine differentiation and communication involving neuropeptides, in physiology and pathophysiology. Peptides such as PACAP, urotensin II and ACTH are implicated in cell growth and differentiation or neurotransmitter/hormone release, during development and in adulthood. Studies will be conducted to determine the role of trophic peptides, and certain genes involved in their effects (selenoprotein T, chromogranins, G protein-coupled receptors) as revealed by transcriptomic and proteomic analyses, in processes of cell differentiation, neuroprotection, and glial and neuro-endocrine tumorigenesis. Using a multidisciplinary approach of neuroscience and neuroendocrinology based on cell imaging, electrophysiology, neurotransmitter/hormone release assays, gene disruption, peptide characterization, etc, in vivo and in vitro, our research groups will contribute to the understanding of basic mechanisms underlying neuronal and neuroendocrine function of neuropeptides. Pre-clinical and clinical investigations will allow us to determine the pathophysiological implications of peptide-associated effects in animal models and human, respectively. Thus, beside the cognitive aspects of our research project, the ultimate goal is to identify, develop and validate therapeutic strategies (e.g. PACAP analogs) as well as diagnostic/prognostic tools (e.g. EM66 biomarker), in collaboration with Rouen CHU services, CIC and IRIB laboratories, national networks (COMETE, PGL-EVA, REHOS, Canceropole), partners in the pharmaceutical industry and numerous international research groups (LARC Neurosciences Network, TransChannel Neuroscience Network, ens@t, GDRI NeurO, Neuromed).

  Main contributions

• Identification of novel neuropeptides and their functions (Urotensine II, 26RFa, EM66)
• Characterization of the transcriptomes of benign and malignant pheochromocytomas
• Identification of a marker of neuroendocrine tumors, EM66
• Identification of a novel mechanism of neuroprotection involving selenoprotein T
• Identification of the neurotrophic effects of PACAP and ODN
• Development of PACAP and ODN analogs resistant to degradation
• Characterization of the mechanism of action of a novel neuropeptide, Urotensin II, in astrocytes
• Validation of an animal model for the study of chemotherapeutics and targeted therapies on cognitive functions
• Identification of the regulatory action of intra-adrenal paracrine factors on aldosterone and cortisol secretion during primary hypercorticism
• Identification of ectopic intra-adrenal ACTH production in macronodular adrenal hyperplasias causing Cushing syndrom.
• Elucidation of the mechanism of the paradoxical reaction of cortisol secretion to dexamethasone during pigmented micronodular hyperplasia of the adrenal