Networks

• GdR 3545 G Protein-coupled Receptors: from physiology to drugs
• GDR 3606 Repro
• Réseau d'enseignement et de recherche en Neurosciences du Nord-Ouest (réseau LARC-Neurosciences)
• Centre de ressources biologique - Germethèque
• Réseau National COMETE-Cancers de la surrénale
• European Network for the Study of Adrenal Tumours (Ens@t)

  Composition

• 63 researchers, engineers, technicians
• 6 post-docs, 23 PhD students

  Facilities

• Cell Imaging Platform PRIMACEN and Proteomics Platform PTP
• 3D imaging
• Animal facility and behavior
• Electrophysiology coupled to imaging/optogenetic in vivo and vitro
• High throughput quantitative PCR
• L2 sectors for human cell culture and retroviral transduction
• NGS facility
• Histology
• Biochemistry

  Activity

The central theme of the four research groups of the INSERM U1239 within IRIB is devoted to neuronal and neuroendocrine differentiation and communication. Several pathologies of the central nervous system (neurodegenerative diseases, lissencephaly, brain tumors) and the neuro-endocrine system (obesity, diabetes, 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 are 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, hormone regulation and 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 contribute to the understanding of basic mechanisms underlying neuronal and neuroendocrine function of neuropeptides. Pre-clinical and clinical investigations 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. Urotensin II, PACAP analogs and signaling targets) 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, Cog-Immuno, Canceropole, ANOCEF, GDR-GPCR, Onconeurotox, OncoThera), partners in the pharmaceutical industry and numerous international research groups (LARC Neurosciences Network, ens@t, ICCTF, the COST Network ERNEST).

  Main contributions

• Characterization of the transcriptomes of benign, incidental and malignant pheochromocytomas
• Characterization of the proteome of neurosecretory cells and identification of major regulators of secretion
• Identification of novel markers and therapies of neuroendocrine and non-neuroendocrine tumors
• Identification of novel mechanisms of neuroprotection and neuroendocrine regulation involving selenoprotein T
• Identification of the neurotrophic effects of PACAP and ODN
• Development of PACAP and ODN analogs resistant to degradation
• Characterization of the chemokine behavior of Urotensin II
• Development and efficacy of UII analogs on subarachnoid hemorrhage
• Identification of chemokine GPCR-induced glioma adhesion and migration
• Original behavioral animal models for the study of the impact of cancer and cancer treatment on cognitive functions
• Identification of ectopic intra-adrenal ACTH production in macronodular adrenal hyperplasias causing Cushing syndrom.
• PRKAR1A inactivating mutation induces occurrence of serotonin regulatory loop stimulating cortisol production in pigmented micronodular hyperplasia of the adrenal
• Elucidation of the role of mast cells in control of aldosterone secretion by using mast-cell deficient mice
• Demonstration that the neuropeptide 26RFa is a novel incretin and a crucial regulator of glucose homeostasis

  Latest publications

2018

• Alim K, Lefranc B, Sopkova-de Oliveira Santos J, Dubessy C, Picot M, Boutin JA, Vaudry H, Chartrel N, Vaudry D, Chuquet J and Leprince J. Design, Synthesis, Molecular Dynamics Simulation, and Functional Evaluation of a Novel Series of 26RFa Peptide Analogues Containing a Mono- or Polyalkyl Guanidino Arginine Derivative. J Med Chem 2018, 61: 10185-10197.
  30358997
• Bahdoudi S, Ghouili I, Hmiden M, do Rego JL, Lefranc B, Leprince J, Chuquet J, do Rego JC, Marcher AB, Mandrup S, Vaudry H, Tonon MC, Amri M, Masmoudi-Kouki O and Vaudry D. Neuroprotective effects of the gliopeptide ODN in an in vivo model of Parkinson's disease. Cell Mol Life Sci 2018, 75: 2075-2091.
  29264673
• Værøy H, Adori C, Legrand R, Lucas N, Breton J, Cottard C, do Rego JC, Duparc C, Louiset E, Lefebvre H, Déchelotte P, Western E, Andersson S, Hökfelt T and Fetissov SO. Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans. Proc Natl Acad Sci U S A 2018, 115: E6576-E6584.
  29941562

2017

• Hamieh A, Cartier D, Abid H, Calas A, Burel C, Bucharles C, Jehan C, Grumolato L, Landry M, Lerouge P, Anouar Y and Lihrmann I. Selenoprotein T is a novel OST subunit that regulates UPR signaling and hormone secretion. EMBO Rep 2017, 18: 1935-1946.
  28928140

2016

• Boukhzar L, Hamieh A, Cartier D, Tanguy Y, Alsharif I, Castex M, Arabo A, El Hajji S, Bonnet JJ, Errami M, Falluel-Morel A, Chagraoui A, Lihrmann I and Anouar Y. Selenoprotein T Exerts an Essential Oxidoreductase Activity That Protects Dopaminergic Neurons in Mouse Models of Parkinson's Disease. Antioxid Redox Signal 2016, 24: 557-74.
  26866473
• Bram Z, Louiset E, Ragazzon B, Renouf S, Wils J, Duparc C, Boutelet I, Rizk-Rabin M, Libé R, Young J, Carson D, Vantyghem MC, Szarek E, Martinez A, Stratakis CA, Bertherat J and Lefebvre H. PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease. JCI Insight 2016, 1: e87958.
  27699247
• Coly PM, Perzo N, Le Joncour V, Lecointre C, Schouft MT, Desrues L, Tonon MC, Wurtz O, Gandolfo P, Castel H and Morin F. Chemotactic G protein-coupled receptors control cell migration by repressing autophagosome biogenesis. Autophagy 2016, 12: 2344-2362.
  27715446
• Guernet A, Mungamuri SK, Cartier D, Sachidanandam R, Jayaprakash A, Adriouch S, Vezain M, Charbonnier F, Rohkin G, Coutant S, Yao S, Ainani H, Alexandre D, Tournier I, Boyer O, Aaronson SA, Anouar Y and Grumolato L. CRISPR-Barcoding for Intratumor Genetic Heterogeneity Modeling and Functional Analysis of Oncogenic Driver Mutations. Mol Cell 2016, 63: 526-38.
  27453044

2015

• Lecointre C, Desrues L, Joubert JE, Perzo N, Guichet PO, Le Joncour V, Brulé C, Chabbert M, Leduc R, Prézeau L, Laquerrière A, Proust F, Gandolfo P, Morin F and Castel H. Signaling switch of the urotensin II vasosactive peptide GPCR: prototypic chemotaxic mechanism in glioma. Oncogene 2015, 34: 5080-94.
  25597409
• Prévost G, Jeandel L, Arabo A, Coëffier M, El Ouahli M, Picot M, Alexandre D, Gobet F, Leprince J, Berrahmoune H, Déchelotte P, Malagon M, Bonner C, Kerr-Conte J, Chigr F, Lefebvre H, Anouar Y and Chartrel N. Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis. Diabetes 2015, 64: 2805-16.
  25858563

  Other Scientific Productions

• PCT/FR2014/053151 - procédés et compositions pharmaceutiques dans le traitement du cancer de la prostate
• WO2017068120 - Code-barres d'endonucléase
• WO2018130790 - Peptide immunomodulateur
• WO2018234556 - Procédés de prévention ou de traitement de la résistance à l'inhibition de l'EGFR dans le cancer
• WO2019068682 - Procédés et compositions pharmaceutiques d’une cardioprotection chez des sujets atteints d’un infarctus du myocarde
• WO2020012025 - Peptidome du venin de la fourmi T. bicarinatum
• EP18306336.1 - Méthodes et compositions pharmaceutiques pour le traitement topique du dysfonctionnement microvasculaire cutané
• EP20305957.1 - Méthodes de traitement de lésions nerveuses
• FR1912084 - Composition pharmaceutique comprenant le mitotane pour une administration par voie orale dans le traitement du carcinome corticosurrénalien et du syndrome de Cushing

► Outils informatiques (logiciel, base de  données)

• Logiciel Mirabel pour l'analyse des cibles des miRNA