Equipe 1 : Génomique fonctionnelle et physiopathologie neuronale et neuroendocrine

Responsable: Dr Youssef Anouar, DR Inserm

Notre projet de recherche vise à caractériser la différenciation et la régulation des cellules productrices de catécholamines (dopamine, adrénaline et noradrénaline) en physiologie et physiopathologie, puis à appliquer les résultats obtenus dans le domaine de la médecine et de la biotechnologie. Ce projet est axé sur deux situations pathologiques, à savoir la maladie de Parkinson et les tumeurs neuroendocrines. La première partie de notre projet comprend des études consacrées à la caractérisation du rôle physiologique et physiopathologique de la Sélénoprotéine T (SelT), un nouveau gène régulé lors de la différenciation des cellules catécholaminergiques, avec trois objectifs principaux: i) étudier le rôle de la SelT dans la neuroprotection contre le stress oxydatif dans la maladie de Parkinson chez des souris sauvages et SelT-déficientes , ii) examiner le rôle de la  SelT dans le développement du cerveau, iii) évaluer l’impact de la SelT dans les régulations neuroendocrines et dans le comportement. Le second thème de notre programme vise à étudier la physiopathologie des tumeurs neuroendocrines telles que les phéochromocytomes et les neuroblastomes, afin de contribuer à la compréhension des voies de tumorigenèse, et définir de nouveaux outils de diagnostic/pronostic et des cibles thérapeutiques spécifiques. Dans ce but, nous caractérisons les transcriptomes (ARNm et microARN) de ces tumeurs et nous identifions les acteurs d’intérêt sur le plan physiopathologique. Notre recherche translationnelle, fondée sur la génomique fonctionnelle, vise à comprendre la physiologie et la physiopathologie des cellules catécholaminergiques et à développer de nouveaux outils biologiques susceptibles d'aider les cliniciens dans la prise en charge de patients atteints de pathologies neuronales ou neuroendocrines affectant ce type cellulaire essentiel.

 

Youssef ANOUAR, DR2 Inserm (HDR) - Coordonnateur équipe 1

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Tél. : 02.35.14.66.61

 

 

Maïté MONTERO-HADJADJE, Professeur Université de Rouen (HDR)

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Tél. : 02.35.14.66.43
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Laurent YON, Professeur Université de Rouen (HDR)

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Tél. : 02.35.14.70.99

 

Isabelle LIHRMANN, CR1 Inserm

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Tél.: 02.35.14.66.26

 

Luca GRUMOLATO, Maître de Conférences Université de Rouen

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Tél.: 02.35.14.66.40
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Christine BUCHARLES, Maître de Conférences Université de Rouen

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Tél.: 02.35.14.67.52

 

Abdeslam CHAGRAOUI, MCU-PH (HDR)

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Tél. : 02.35.14.66.41

 

Christophe DUBESSY, Maître de Conférences Université de Rouen

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Tél.: 02.35.14.67.52

 

Anthony FALLUEL-MOREL, Maître de Conférences, Université de Rouen

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Tél.: 02.35.14.66.41
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Lydie JEANDEL, Maître de Conférences, Université de Rouen

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Tél.: 02 35 14 66 43

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Dorthe CARTIER-KIRKEGAARD, IE Inserm

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Tél. : 02.35.14.66.26

 

Loubna BOUKHZAR, CDD Université

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Tél. : 02.35.14.69.45

 

 

David GODEFROY, IE Université

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Tél. : 02.35.14.69.45

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  1. Courel, M., Soler-Jover, A., Rodriguez-Flores, J.L., Mahata, S.K., Elias, S., Montero-Hadjadje, M., Anouar, Y., Giuly, R.J., O'Connor, D.T. and Taupenot, L.: Pro-hormone Secretogranin II regulates dense core secretory granule biogenesis in catecholaminergic cells. J. Biol. Chem. 285:10030-10043 (2010). (IF = 5,32)

  2. Elias, S., Delestre, C., Courel, M., Anouar, Y. and Montero-Hadjadje, M.: Chromogranin A as a crucial factor in the sorting of peptide hormones to secretory granules. Cell Mol Neurobiol. 30:1189-1195 (2010).

  3. El Yamani, F.Z., Yon, L., Guérin, M., El Ouezzani, S., Alaoui, A., Chartrel, N., Anouar, Y. and Magoul, R.: EM66-containing neurones in the hypothalamic parvicellular paraventricular nucleus of the rat: no plasticity related to acute immune stress. Neuro Endocrinol Lett. 31:609-615 (2010). (IF = 1,62)

  4. Guérin, M., Guillemot, J., Thouënnon, E., Pierre, A., El-Yamani, F.Z., Montero-Hadjadje, M., Dubessy, C., Magoul, R., Lihrmann, I., Anouar, Y. and Yon, L.: Granins and their derived peptides in normal and tumoral chromaffin tissue: Implications for the diagnosis and prognosis of pheochromocytoma. Regul Pept. 165:21-29 (2010). (IF = 2,05)

  5. Thouënnon, E., Pierre, A., Tanguy, Y., Guillemot, J., Manecka, D.L., Guérin, M., Ouafik, L., Muresan, M., Klein, M., Bertherat, J., Lefebvre, H., Plouin, P.F., Yon, L. and Anouar, Y.: Expression of trophic amidated peptides and their receptors in benign and malignant pheochromocytomas: high expression of adrenomedullin RDC1 receptor and implication in tumoral cell survival. Endocr. Relat. Cancer 17:637-651 (2010). (IF = 5,68)

  6. Thouennon, E., Pierre, A., Yon, L., Anouar, Y.: Expression of trophic peptides and their receptors in chromaffin cells and pheochromocytoma. Cell Mol Neurobiol. 30:1383-89 (2010).

  7. Laborie, C., Molendi-Coste, O., Breton, C., Montel, V., Vandenbulcke, F., Grumolato, L., Anouar, Y. and Vieau D.: Maternal perinatal undernutrition has long-term consequences both on morphology, function and gene expression of the adrenal medulla in the adult male rat. J. Neuroendocrinol. 23:711-724 (2011). (IF = 3,70)

  8. Parmentier, C., Hameury, E., Dubessy, C., Quan, F.B., Habert, D., Calas, A., Vaudry, H., Lihrmann, I. and Tostivint, H.: Distinct urotensin II-related peptides in zebrafish provides new insight into the evolutionary history of the urotensin II gene family. Endocrinology 152:2330-2341 (2011). (IF=4,75)

  9. Sokolowsk, K., Falluel-Morel, A., Zhou, X. and Dicicco-Bloom, E.: Methylmercury (MeHg) elicits mitochondrial-dependent apoptosis in developing hippocampus and acts at low exposures.  Neurotoxicology 32:535-544 (2011).

  10. Tanguy, Y., Falluel-Morel, A., Arthaud, S., Boukhzar, L., Manecka, D.L., Chagraoui, A., Prevost, G., Elias, S., Dorval-Coiffec, I., Lesage, J., Vieau, D., Lihrmann, I., Jégou, B. AND Anouar, Y.: The PACAP-Regulated Gene Selenoprotein T Is Highly Induced in Nervous, Endocrine, and Metabolic Tissues during Ontogenetic and Regenerative Processes. Endocrinology, 152:4322-4335 (2011). (IF = 5,1)

  11. Cruz-Garcia, D., Diaz-Ruiz, A., Rabanal-Ruiz, Y., Peinado, J.R., Gracia-Navarro, F., Castano, J.P., Montero-Hadjadje, M., Tonon, M.C., Vaudry, H., Anouar, Y., Vazquez-Martinez, R. and Malagon, M.M.: The Golgi-associated long oiled-coil protein NECCI participates in the control of the regulated secretory pathway in PC12 cells. Biochem. J. 443:387-396 (2012). (IF= 4,89)

  12. Elias, S., Delestre, C., Ory, S., Marais, S., Courel, M., Vazquez-Martinez, R., Bernard, S., Coquet, L., Malagon, M.M., Driouich, A., Chan, P., Gasman, S., Anouar, Y. and Montéro-Hadjadje, M.: Chromogranin A-induces the biogenesis of granules with calcium- and actin-dependent dynamics and exocytosis in constitutively secreting cells. Endocrinology 153:4444-4456 (2012). (IF = 4,71)

  13. Falluel-Morel, A., Lin, L., Sokolowski, K., McCandlish, E., Buckley, B. and DiCicco-Bloom, E.: N-acetyl cysteine (NAC) treatment reduces mercury-induced neurotoxicity in the developing rat hippocampus. J. Neurosci. Res., 90:743-750 (2012).

  14. Guillemot, J., Thouennon, E., Guerin, M., Vallet-Erdtmann, V., Ravni, A., Montero-Hadjadje, M., Lefebvre,  H., Klein, M., Muresan, M., Seidah, N.G., Anouar, Y. and Yon, L.: Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66. J. Mol. Endocrinol. 48:115-127 (2012) (IF = 3,22)

  15. Prévost, G., Eas, F., Duparc, C., Cauliez, B., Laquérrière, A., Fréger, P., Lefebvre, H. and Kuhn, J.M.: Study of the involvement of pancreastatin in the physiopathology of diabetes mellitus associated with nonsecreting pituitary adenomas. Horm. Metab. Res. 44:861-865 (2012) (IF=2,68)

  16. Alonzeau, J., Alexandre, D., Jeandel, L., Courel, M., Hautot, C., El Yamani, F.Z., Gobet, F., Leprince, J., Magoul, R., Amarti, A., Pfister, C., Yon, L., Anouar, Y. and Chartrel, N.: The neuropeptide 26RFa is expressed in human prostate cancer and stimulates the neuroendocrine differentiation and the migration of androgeno-independent prostate cancer cells. Europ. J. Cancer 49:511-519 (2013) (IF=5,5).

  17. Diaz-Ruiz, A.: Rabanal-Ruiz, Y., Travez, A., Gracia-Navarro, F., Cruz-Garcia, D., Montero-Hadjadje, M., Anouar, Y., Gasman, S., Vitale, N., Vazquez-Martinez, R. and Malagon, M.: The long coiled-coil protein NECC2 is associated to caveolae and modulates NGF/TrkA signaling in PC12 cells. PLoS One  Sep 6;8(9):e73668 (2013). (IF = 4,35)

  18. El Yamani, F.Z., Yon, L., Guérin, M., El Ouezzani, S., Alaoui, A., Chartrel, N., Anouar, Y. and Magoul, R.: Immunocytochemical expression of EM66 within the hypothalamic parvocellular paraventricular nucleus: colocalization with CRH and TRH but no plasticity related to acute stress and thyroidectomy in the rat. Regul. Pept. 182:28-34 (2013) (IF = 2,16)

  19. Grumolato L., Liu G., Haremaki T., Mungamuri S.K., Mong P., Akiri G., Lopez-Bergami P., Arita A., Anouar Y., Mlodzik M., Ronai Z.A., Brody J., Weinstein D.C. and Aaronson S.A. β-Catenin-independent activation of TCF1/LEF1 in human hematopoietic tumor cells through interaction with ATF2 transcription factors. PLoS Genetics 9: e1003603 (2013). (IF = 8,52)

  20. Haissaguerre, M., Courel, M., Caron, P., Denost, S., Dubessy, C., Gosse, P., Appavoupoulle, V., Belleannée, G., Jullié, M.L., Montero-Hadjadje, M., Yon, L., Corcuff, J.B., Fagour, C., Mazerolles, C., Wagner, T., Nunes, M.L., Anouar, Y. and Tabarin A.: Normotensive incidentally discovered pheochromocytomas display specific biochemical, cellular, and molecular characteristics. J. Clin. Endocrinol. Metab. 98:4346-4354 (2013) (IF = 6,43)

  21. Lefebvre, H., Prevost, G. and Louiset, E.: Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticisms. Eur. J. Endocrinol. 169:R115-R138 (2013).

  22. Manecka, D.L., Mahmood, F., Grumolato, L., Lihrmann, I. and Anouar, Y.: Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) promotes both survival and neuritogenesis in PC12 cells through activation of nuclear factor-kappaB (NF-kB) pathway involvement of extracellular signal-regulated kinase (ERK), calcium and c-REL. J. Biol. Chem. 288:14936-14948 (2013) (IF = 5,32)

  23. Mungamuri, S.K., Murk, W., Grumolato, L., Bernstein, E. and Aaronson, S.A.: Chromatin Modifications Sequentially Enhance ErbB2 Expression in ErbB2-Positive Breast Cancers. Cell Reports S2211-1247(13)00517-2. 10.1016/j.celrep.2013.09.009. (2013)

  24. Prevost, G., Arabo, A., Jian, L., Quelennec, E., Cartier, D., Hassan, S., Falluel-Morel, A., Tanguy, Y., Gargani, S., Lihrmann, I., Kerr-Conte, J., Lefebvre, H., Pattou, F. and Anouar, Y.: The PACAP-regulated gene selenoprotein T is abundantly expressed in mouse and human β cells and its targeted inactivation impaires glucose tolerance. Endocrinology 154:3796-3806 (2013). (IF = 4,75)

  25. Serysheva, E., Berhane, H., Grumolato, L., Demir, K., Balmer, S., Bodak, M., Boutros, M., Aaronson, S., Mlodzik, M. and Jenny, A.: Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling. EMBO Reports 14:718-25 (2013)

  26. Tostivint, H., Quan, F.B., Bougerol, M., Kenigfest, N.B. and Lihrmann, I.: Impact of gene/genome duplications on the evolution of the urotensin II and somatostatin families. Gen. Comp. Endocrinol. 2013, doi:pii:S0016-6480(13)00005-1.10.1016/j.ygcen.2012.12.015. (2013) (IF=2,73)

  27. Balland, E., Dam, J., Langlet, F., Caron, E.; Steculorum, S., Messina, A., Rasika, S., Falluel-Morel, A., Anouar, Y., Behouck, B., Trinquet, E., Jockers, R., Bouret, S.G. and Prévot, V.: Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metab. 19:293-301 (2014) (IF = 14,62)

  28. Guillemot, J., Guérin, M., Thouennon, E., Montero, M., Leprince, J., Lefebvre, H., Klein, M., Museran, M., Anouar, Y., and Yon, Y.: Combined measurement of granin and granin-derived peptides improves the diagnosis of pheochromocytoma. PLos One 9:e88698 (2014) (IF = 4,35)

     

  29. Bucharles, C., Bizet, P., Arthaud, S., Arabo, A., Leprince, J., Lefranc, B., Cartier, D., Anouar, Y. and Lihrmann, I.: Concordant localization of functional urotensin II and urotensin II-related peptide binding sites in the rat brain: atypical occurrence close to the fourth ventricle. J. Comp. Neurol. (in press).

  30. Haissaguerre, M., Courel, M., Caron, P., Denost, S., Dubessy, C., Gosse, P., Appavoupoulle, V., Belleannée, G., Jullié, M.L., Montero-Hadjadje, M., Yon, L., Corcuff, J.B., Fagour, C., Mazerolles, C., Wagner, T., Nunes, M.L., Anouar, Y., Tabarin, A.: Normotensive incidentally discovered pheochromocytomas display specific biochemical, cellular and molecular characteristics. J. Clin. Endocrinol. Metab. (in press).  (IF = 6,20)

  31. Lefebvre, H., Prévost, G. and Louiset, E.: Could targeting hormone receptors be an effective strategy in management of adrenal hyperplasia? Int. J. Endocr. Oncol. (in press)


 

 

 

Partenariats régionaux

 

 

  • EA 4358 (P. Lerouge/A. Driouich, Rouen)
  • ERI28 « NeoVasc » (B. Gonzalez, Rouen)
  • Inserm U919 (D. Vivien, Caen)
  • IRCOF, CNRS UMR 6014 (G. Gouhier, Rouen)
  • Equipe CERVOxy de l’UMR 6232 (M. Bernaudin)
  • Service d’Endocrinologie Diabète et Maladies Métaboliques (J.M. Kuhn/H. Lefebvre)
  • CIC du CHU de Rouen (J. Weber)

 

 

Partenariats nationaux

 

 

 

  • Inserm U800 (N. Prevarskaya, Lille)
  • Inserm U625 (B. Jégou, Rennes)
  • CNRS UMR 7168 / LC2 (S. Gasman, V. Lelièvre, Strasbourg)
  • Institut Gustave Roussy (E. Baudin, Paris)
  • Hôpital Européen Georges Pompidou (P.F. Plouin, Paris)
  • Inserm U970 (A.P. Gimenez, Paris)
  • Inserm U911 (L. Ouafik, Marseille)
  • Unité de Neurosciences et Physiologie Adaptatives, UPRES EA 4052 (D. Vieau, Lille)
  • CNRS UMR 6214, Inserm U771 (N. Guerineau, Montpellier)
  • Inserm UMR 549 (J. Epelbaum, Paris)

 

 

Partenariats internationaux

 

 

 

  • Research Group Functional Genomics and Proteomics (L. Schoofs, Louvain)
  • Université de Dresden (G. Eisenhofer, Allemagne)
  • Université de Coimbra (C. Cavadas, Portugal)
  • Université de Fès (R. Magoul, Maroc)
  • Université de Tetouan
  • CHU Lausanne (E. Grouzmann, Suisse)
  • Université de Cordoue (M. Malagon, Espagne)
  • UCSD (L. Taupenot, San Diego, USA)
  • NIMH (L.E. Eiden, Bethesda, USA)
  • NHGRI (A.G. Elkahloun, Bethesda, USA)

 

Subcategories