Logo INRS
English

By anne-marie.dubois - Posted on 21 décembre 2016

Version imprimable

 

Expertises

Chimie médicinale et pharmacologie
 
Centre INRS–Institut Armand-Frappier
Institut national de la recherche scientifique
531, boulevard des Prairies
Laval (Québec) H7V 1B7
CANADA
 
450 687-5010 poste 8816
 
 
 

 


 

Intérêt de recherche

 

Les peptides constituent une classe de molécules biologiques possédant diverses fonctions. Ainsi, ils peuvent agir comme hormones, facteurs de croissance, agents de signalisation cellulaire, antibiotiques, neurotransmetteurs, neuromodulateurs, etc. Ce spectre d'activités de même que la spécificité relative des peptides et leur puissance d'action en font des constituants biologiques dont la détermination des rôles précis constitue un objectif majeur chez les scientifiques oeuvrant dans le domaine biomédical. Ainsi, la compréhension de leur mode d'action à l'échelle moléculaire représente un élément essentiel à l'identification de sondes biologiques du fonctionnement et du développement des organismes, en plus de faciliter la mise au point de dérivés peptidiques ou peptidomimétiques potentiellement utiles comme outils pharmacologiques ou agents thérapeutiques.
 
Nos travaux ciblent donc certaines familles de peptides caractérisées entre autres par le rôle unique qu'elles jouent au niveau des systèmes nerveux, endocrinien et cardio-vasculaire. Nous souhaitons ainsi mieux définir les fonctions biologiques associées à certaines familles de peptides dans des états physiologiques normaux et pathologiques. De plus, les composés polypeptidiques étudiés servent de peptides-modèles pour l'établissement de caractéristiques structurales et biologiques de base, estimées par diverses méthodes spectroscopiques, théoriques et pharmacologiques. Des dérivés synthétiques comportant des modifications chimiques sont alors assemblés puis évalués biologiquement afin d'explorer plus à fond certains paramètres structuraux des molécules.
 
Cette approche permet d'établir les corrélations fines existant entre l'organisation spatiale des peptides et leurs propriétés biologiques. Parallèlement, l'identification des acides aminés et de façon plus précise des groupements chimiques de la molécule assurant la liaison du peptide à son récepteur cellulaire, lequel est responsable de la réponse biologique, oriente les travaux vers la conception de nouveaux dérivés dont l'arrangement structural respecte la topographie du récepteur protéique. Ces substances dites peptidomimétiques, puisqu'elles reproduisent les effets de peptides parfois complexes et ce, même si leur taille et leur nature sont généralement différentes de celles de la molécule-modèle, peuvent s'avérer des outils précieux pour caractériser des phénomènes physiologiques et pathologiques.
 
* Maintenant professeur honoraire suite à son départ à la retraite
 

Projets récents

 

Notez s'il-vous-plaît que je suis maintenant à la retraite. Je garde toutefois un lien avec l'INRS via le statut de professeur honoraire. Néanmoins, mes activités de recherche sont dorénavant limitées et en particulier, je ne recrute plus de stagiaires, ni d'étudiants gradués.
 
Les projets décrits ci-dessous demeurent actifs. Les travaux portant sur le peptide PACAP et les polypeptides isolés des venins sont poursuivis en collaboration avec mon collègue de l'INRS-IAF, le Pr David Chatenet, tandis que les études sur le PulmoBind sont toujours en cours en association avec le Dr Jocelyn Dupuis de l'Institut de cardiologie de Montréal. Le programme de recherche portant sur UII/UT est maintenant mené par le Pr Chatenet.
 
Développement de dérivés neuroprotecteurs du pituitary adenylate cyclase-activating polypeptide (PACAP)
Le neuropeptide PACAP exerce une forte activité protectrice contre la neurodégénérescence dans certains modèles physiopathologiques d’atteintes du cerveau tels l’AVC et le Parkinson. Plus particulièrement, lorsqu’injecté par voie intraveineuse après un choc ischémique, le PACAP peut stopper l’expansion de la zone infarcie dans les régions cérébrales lésées. Toutefois, à cause de sa nature peptidique, cette substance possède des propriétés pharmacocinétiques qui limitent son utilisation comme agent thérapeutique. Donc, dans le cadre de nos études, en collaboration avec des chercheurs de l’Université de Rouen (FR), des analogues du PACAP sont synthétisés dans le but de leur procurer une stabilité métabolique accrue et d'améliorer leur sélectivité d'action. Cet objectif est atteint au moyen de modifications chimiques de la molécule.
 
Développement de dérivés de l’adrénomédulline (AM) humaine capables de chélater un radioisotope et caractérisation de leurs propriétés en imagerie pulmonaire
La médecine nucléaire utilise actuellement les macroaggrégats d’albumine (MAA) comme traceurs de la circulation dans les poumons. Malheureusement, la taille de ces molécules ne permet pas la visualisation de la microcirculation pulmonaire ce qui nuit au diagnostic précoce. En collaboration avec une équipe de recherche de l’Institut de cardiologie de Montréal, nous avons montré que l’adrénomédulline (AM), un peptide de 52 acides aminés, est capable de chélater le 99mTc et que le complexe ainsi formé possède une affinité très significative pour les poumons. Bien que ce nouvel outil d’imagerie offrait l’avantage d’être plus petit que les MAA, il n'était pas encore optimal. De plus, la longueur du peptide constituait un défi sérieux pour une production facile et un usage clinique courant. Depuis, nous avons réussi à produire un dérivé, le PulmoBind, qui a traversé les étapes des phases cliniques I et II.
 
Caractérisation structurale et pharmacologique du peptide urotensine II et de son récepteur UT
L’urotensine II (UII) est un peptide présent dans divers systèmes biologiques dont les systèmes nerveux et cardio-vasculaires. Au niveau de ce dernier, il a été montré que certains tissus étaient très sensibles à UII puisque des contractions des muscles lisses vasculaires peuvent être induites à des concentrations de ligand de l’ordre du picomolaire. Bien que son efficacité et sa durée d’action soient relativement faibles, sa capacité à induire une action à des concentrations aussi faibles en fait le composé vasoconstricteur le plus puissant décrit jusqu’à maintenant. Cet effet nous a amenés à explorer le mode d’interaction à l’échelle moléculaire du peptide UII avec son récepteur membranaire appelé UT.
 
Identification et caractérisation de peptides bioactifs isolés à partir du venin d'un serpent d'Asie du Sud-Est
Dans le cadre d'une collaboration avec des partenaires du Vietnam, nous avons évalué les propriétés biologiques de dérivés peptidiques isolés du venin d'un cobra retrouvé en Asie du Sud-Est. Le venin est un cocktail complexe de nombreuses molécules aux activités diverses au niveau des systèmes physiologiques. Fruits de millions d'années d'évolution, les substances retrouvées dans le venin présentent des caractéristiques biologiques uniques qui peuvent s'avérer très utiles pour le développement de nouvelles stratégies thérapeutiques et/ou diagnostiques. Nos travaux ont permis l'isolation et la caratérisation d'un peptide capable d'induire la sécrétion d'insuline. Au moyen d'études structurales, la molécule a pu être amélioriée et elle constitue un canevas prometteur pour la mise au point d'un nouvel agent pour le traitement du diabète.

 

Publications

 

405. CHATENET, D., FOURNIER, A. & BOURGAULT, S. (2016)

PACAP-derived carriers: Mechanisms and applications,

Pituitary adenylate cyclase-activating polypeptide – PACAP, D. Reglodi & A. Tamas Ed, Springer, 133-148

 

404.FOURNIER, A., BOURGAULT, S. & CHATENET, D. (2016)

The pharmacophoric determinants of PACAP,

Pituitary adenylate cyclase-activating polypeptide – PACAP, D. Reglodi & A. Tamas Ed, Springer, 111-132

 

403.LEVAC, X., HAREL, F., FINNERTY, V., NGUYEN, Q.T., LÉTOURNEAU, M., MARCIL, S., FOURNIER, A. & DUPUIS, J. (2016)

Evaluation of pulmonary perfusion by SPECT imaging using an endothelial cell tracer in supine humans and dogs, European Journal of Nuclear Medicine and Molecular Imaging Research, 6, 43, 1-9

 

402.THERRIEN, A., FOURNIER, A. & LAFLEUR, M. (2016)

Role of the Cationic C-Terminal Segment of Melittin on Membrane Fragmentation,

The Journal of Physical Chemistry – B, 110, 400-410

 

401.DOUIRI, S., BAHDOUDI, S., HAMDI, Y., CUBI, RT., BASILLE, M., FOURNIER, A., VAUDRY, H., TONON, M.C., AMRI, M., VAUDRY, D. & MASMOUDI-KOUKI, O. (2016)

Involvement of endogenous antioxydant systems in the protective activity of pituitary adenylate cyclase-activating polypeptide against hydrogen peroxide-induced oxidative damages in cultures rat astrocytes,

Journal of Neurochemistry, 137, 913-930

 

400.BOISVILLIERS, M.D., PERRIN, F., HEBACHE, S., BALANDRE, A.C., BENSALMA, S., GARNIER, A., VAUDRY, D., FOURNIER, A., FESTY, F., MULLER, J.M. & CHARDÉNEAU, C. (2016)

VIP and PACAP analogs regulate therapeutic targets in high-risk neuroblastoma cells,

Peptides, 78, 30-41

 

399.LAMINE-AJILI, A., FAHMY, A. M., LÉTOURNEAU, M., CHATENET, D., LABONTÉ, P., VAUDRY, D. & FOURNIER, A. (2016) Effect of the pituitary adenylate cyclase-activating polypeptide on the autophagic activation observed inin vitro andin vivo models of Parkinson’s disease,

Biochimica et Biophysica Acta – Molecular Basis of Disease, 1862, 688-695

 

398.TADEVOSYAN, A., VILLENEUVE, L. R., FOURNIER, A., CHATENET, D., NATTEL, S. & ALLEN, B. G. (2016)

Caged ligands to study the role of intracellular GPCRs,

Methods, 92, 72-77

 

 

397.LAMINE, A., LÉTOURNEAU, M., DOAN, N. D., MAUCOTEL, J., COUVINEAU, A., VAUDRY, H., CHATENET, D., VAUDRY, D. & FOURNIER, A. (2016)

Characterizations of a synthetic pituitary adenylate cyclase-activating polypeptide analog displaying potent neuroprotective activity and reduced in vivo cardiovascular side effects in a Parkinson's disease model,

Neuropharmacology, 108, 440-450

 

 

396.CHATENET, D., BOURGAULT, S. & FOURNIER, A. (2015)

Design and application of light-activated probes for cellular signaling,

Methods in Molecular Biology, 1234, 17-30

 

 

395.VAUDRY, H., LEPRINCE, J., CHATENET, D., FOURNIER, A., LAMBERT, D. G., LE MEVEL, J. C., OHLSTEIN, E. H., SCHWERTANI, A., TOSTIVINT, H. & VAUDRY, D. (2015)

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II-Related Peptide, and Their Receptor: From Structure to Function,

Pharmacological Reviews, 67, 1, 214-58

 

 

394.HAREL, F., LEVAC, X., NGUYEN, Q. T., LÉTOURNEAU, M., MARCIL, S., FINNERTY, V., COSSETTE, M., FOURNIER, A. & DUPUIS, J. (2015)

Molecular imaging of the human pulmonary vascular endothelium using an adrenomedullin receptor ligand,

Molecular Imaging, 14, 1-13

 

 

393.TADEVOSYAN, A., LÉTOURNEAU, M., FOLCH, B., DOUCET, N., VILLENEUVE, L. R., MAMARBACHI, A. M., PÉTRIN, D., HÉBERT, T. E., FOURNIER, A., CHATENET, D., ALLEN, B. G. & NATTEL, S. (2015)

Photoreleasable ligands to study intracrine angiotensin II signalling,

Journal of Physiology, 593, 3, 521-539

 

 

392. JOLIVEL, V., ARTHAUD, S., BOTIA, B., PORTAL, C., DELEST, B., CLAVÉ, G., LEPRINCE, J., ROMIEU, A., RENARD, P. Y., TOUZANI, O., LIGERET, H., NOACK, P., MASSONNEAU, M., FOURNIER, A., VAUDRY, H. & VAUDRY, D. (2014)

Biochemical Characterization of a Caspase-3 Far-red Fluorescent Probe for Non-invasive Optical Imaging of Neuronal Apoptosis,

Journal of Molecular Neuroscience, 54, 3, 451-462

 

 

391.SEABORN, T., RAVNI, A., AU, R., CHOW, B. K. C., FOURNIER, A., WURTZ, O., VAUDRY, H., EIDEN, L. E. & VAUDRY, D. (2014)

Induction of serpinb1a by PACAP or NGF is required for PC12 cells survival after serum withdrawal,

Journal of Neurochemistry, 131, 1, 21-32

 

 

390.TCHOUMI NEREE, A., NGUYEN, P. T., CHATENET, D., FOURNIER, A. & BOURGAULT, S. (2014)

Secondary conformational conversion is involved in glycosaminoglycans-mediated cellular uptake of the cationic cell-penetrating peptide PACAP,

FEBS Letters, 588, 24, 4590-4596

 

 

 

389. RAOULT, E., BÉNARD, M., KOMURO, H., LEBON, A., VIVIEN, D., FOURNIER, A., VAUDRY, H., VAUDRY, D. & GALAS, L. (2014)

Cortical-layer-specific effects of PACAP and tPA on interneuron migration during post-natal development of the cerebellum,

Journal of Neurochemistry, 130, 2, 241-254

 

 

388. NGUYEN, T. T., FOLCH, B., LETOURNEAU, M., TRUONG, N. H., DOUCET, N., FOURNIER, A. & CHATENET, D. (2014)

Design of a truncated cardiotoxin-I analogue with potent insulinotropic activity,

Journal of Medicinal Chemistry, 57, 6, 2623-33

 

 

387.CHATENET, D., FOLCH, B., FEYTENS, D., LÉTOURNEAU, M., TOURWÉ, D., DOUCET, N. & FOURNIER, A. (2013)

Development and pharmacological characterization of conformationally constrained urotensin II-related peptide agonists,

Journal of Medicinal Chemistry, 56, 23, 9612-9622

 

 

386.VAUDRY, D., NAKAMACHI, T., BASILLE, M., WURTZ, O., FOURNIER, A., VAUDRY, H. & SHOIDA, S. (2013)

PACAPHandbook of Biologically Active Peptides Second Edition ed., 889-897

 

 

385. VAUDRY, D., BUREL, D., GALAS, L., LACAILLE, H., DUTERTE-BOUCHER, D., CHATENET, D., FOURNIER, A. & VAUDRY, H. (2013)

PACAPHandbook of Biologically Active Peptides Second Edition ed., 1038-1043

 

 

384. BASILLE-DUGAY, M., VAUDRY, H., FOURNIER, A., GONZALEZ, B. & VAUDRY, D. (2013)

Activation of PAC1 receptors in rat cerebellar granule cells stimulates both calcium mobilization from intracellular stores and calcium influx through N-type calcium channels,

Frontiers in Endocrinology, 4, MAY,

 

 

383. VANIOTIS, G., GLAZKOVA, I., MERLEN, C., SMITH, C., VILLENEUVE, L. R., CHATENET, D., THERIEN, M., FOURNIER, A., TADEVOSYAN, A., TRIEU, P., NATTEL, S., HÉBERT, T. E. & ALLEN, B. G. (2013)

Regulation of cardiac nitric oxide signaling by nuclear β-adrenergic and endothelin receptors,

Journal of Molecular and Cellular Cardiology, 62, 58-68

 

 

382. MERLEN, C., FARHAT, N., LUO, X., CHATENET, D., TADEVOSYAN, A., VILLENEUVE, L. R., GILLIS, M. A., NATTEL, S., THORIN, E., FOURNIER, A. & ALLEN, B. G. (2013)

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes,

Journal of Molecular and Cellular Cardiology, 62, 189-202

 

 

381. LETOURNEAU, M., NGUYEN, Q. T., HAREL, F., FOURNIER, A. & DUPUIS, J. (2013)

PulmoBind, an Adrenomedullin-Based Molecular Lung Imaging Tool,

Journal of Nuclear Medicine, 54, 10, 1789-96

 

 

380. CHATENET, D., LÉTOURNEAU, M., NGUYEN, Q. T., DOAN, N. D., DUPUIS, J. & FOURNIER, A. (2013)

Discovery of new antagonists aimed at discriminating UII and URP-mediated biological activities: Insight into UII and URP receptor activation,

British Journal of Pharmacology, 168, 4, 807-821

 

 

379. FOURNIER, A., CHATENET, D. & LETOURNEAU, M. (2012)

Novel agonists and antagonists of the urotensinergic system and their cardiovascular effectsCopyright (C) 2013 American Chemical Society (ACS). All Rights Reserved., 86pp.

 

 

378. DOAN, N. D., LÉTOURNEAU, M., VAUDRY, D., DOUCET, N., FOLCH, B., VAUDRY, H., FOURNIER, A. & CHATENET, D. (2012)

Design and characterization of novel cell-penetrating peptides from pituitary adenylate cyclase-activating polypeptide,

Journal of Controlled Release, 163, 2, 256-265

 

 

377. NGUYEN, T. T. N., FOLCH, B., LÉTOURNEAU, M., VAUDRY, D., TRUONG, N. H., DOUCET, N., CHATENET, D. & FOURNIER, A. (2012)
Cardiotoxin-I: An Unexpectedly Potent Insulinotropic Agent .
Chembiochem , 13, 12, 1805-1812
 

 

376. DOAN, N. D., NGUYEN, T. T. M., LETOURNEAU, M., TURCOTTE, K., FOURNIER, A. & CHATENET, D. (2012)
Biochemical and pharmacological characterization of nuclear urotensin-II binding sites in rat heart .
British Journal of Pharmacology , 166, 1, 243-257
 

 

375. NGUYEN, T. T., LÉTOURNEAU, M., CHATENET, D. & FOURNIER, A. (2012)
Presence of urotensin-II receptors at the cell nucleus: Specific tissue distribution and hypoxia-induced modulation .
International Journal of Biochemistry and Cell Biology , 44, 4, 639-47
 

 

374. DOAN, N. D., CHATENET, D., LÉTOURNEAU, M., VAUDRY, H., VAUDRY, D. & FOURNIER, A. (2012)
Receptor-independent cellular uptake of pituitary adenylate cyclase-activating polypeptide .
Biochimica et Biophysica Acta , 1823, 4, 940-949
 

 

373. CHATENET, D., NGUYEN, Q.-T., LETOURNEAU, M., DUPUIS, J. & FOURNIER, A. (2012)
Urocontrin, a novel UT receptor ligand with a unique pharmacological profile .
Biochemical Pharmacology , 83, 5, 608-615
 

 

372. TAM, J. K., LAU, K. W., LEE, L. T., CHU, J. Y., NG, K. M., FOURNIER, A., VAUDRY, H. & CHOW, B. K. (2011)
Origin of secretin receptor precedes the advent of tetrapoda: evidence on the separated origins of secretin and orexin .
PLoS ONE , 6, 4, e19384
 

 

371. SEABORN, T., MASMOUDI-KOULI, O., FOURNIER, A., VAUDRY, H. & VAUDRY, D. (2011)
Protective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) against apoptosis .
Current Pharmaceutical Design , 17, 3, 204-14
 

 

370. RAOULT, E., ROUSSEL, B. D., BENARD, M., LEFEBVRE, T., RAVNI, A., ALI, C., VIVIEN, D., KOMURO, H., FOURNIER, A., VAUDRY, H., VAUDRY, D. & GALAS, L. (2011)
Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates the expression and the release of tissue plasminogen activator (tPA) in neuronal cells: involvement of tPA in the neuroprotective effect of PACAP .
Journal of Neurochemistry , 119, 5, 920-931
 

 

369. MASMOUDI-KOUKI, O., DOUIRI, S., HAMDI, Y., KADDOUR, H., BAHDOUDI, S., VAUDRY, D., BASILLE, M., LEPRINCE, J., FOURNIER, A., VAUDRY, H., TONON, M. C. & AMRI, M. (2011)
Pituitary adenylate cyclase-activating polypeptide protects astroglial cells against oxidative stress-induced apoptosis .
Journal of Neurochemistry , 117, 3, 403-11
 

 

368. FU, Y., LÉTOURNEAU, M., CHATENET, D., DUPUIS, J. & FOURNIER, A. (2011)
Characterization of iodinated adrenomedullin derivatives suitable for lung nuclear medicine .
Nuclear Medicine and Biology , 38, 6, 867-74
 

 

367. EL KEBIR, D., ZHANG, Y., POTEMPA, L. A., WU, Y., FOURNIER, A. & FILEP, J. G. (2011)
C-reactive protein-derived peptide 201-206 inhibits neutrophil adhesion to endothelial cells and platelets through CD32 .
Journal of Leukocyte Biology , 90, 6, 1167-1175
 

 

366. DOAN, N. D., NGUYEN, T. T., LETOURNEAU, M., TURCOTTE, K., FOURNIER, A. & CHATENET, D. (2011)
Biochemical and Pharmacological Characterization of Nuclear Urotensin II Binding Sites in Rat Heart .
British Journal of Pharmacology ,
 

 

365. DOAN, N. D., BOURGAULT, S., DEJDA, A., LETOURNEAU, M., DETHEUX, M., VAUDRY, D., VAUDRY, H., CHATENET, D. & FOURNIER, A. (2011)
Design and in vitro characterization of PAC1/VPAC1-selective agonists with potent neuroprotective effects .
Biochemical Pharmacology , 81, 4, 552-561
 

 

364. DEJDA, A., SEABORN, T., BOURGAULT, S., TOUZANI, O., FOURNIER, A., VAUDRY, H. & VAUDRY, D. (2011)
PACAP and a novel stable analog protect rat brain from ischemia: Insight into the mechanisms of action .
Peptides , 32, 6, 1207-1216
 

 

363. DEJDA, A., BOURGAULT, S., DOAN, N. D., LETOURNEAU, M., COUVINEAU, A., VAUDRY, H., VAUDRY, D. & FOURNIER, A. (2011)
Identification by photoaffinity labeling of the extracellular N-terminal domain of PAC1 receptor as the major binding site for PACAP .
Biochimie , 93, 4, 669-677
 

 

362. BOURGAULT, S., CHATENET, D., WURTZ, O., DOAN, N. D., LEPRINCE, J., VAUDRY, H., FOURNIER, A. & VAUDRY, D. (2011)
Strategies to Convert PACAP from a Hypophysiotropic Neurohormone Into a Neuroprotective Drug .
Current Pharmaceutical Design , 17, 10, 1002-1024
 

 

361. BOTIA, B., JOLIVEL, V., BUREL, D., LE JONCOUR, V., ROY, V., NAASSILA, M., BENARD, M., FOURNIER, A., VAUDRY, H. & VAUDRY, D. (2011)
Neuroprotective effects of PACAP against ethanol-induced toxicity in the developing rat cerebellum .
Neurotoxicity Research , 19, 3, 423-34
 

 

360. VAUDRY, H., DO REGO, J. C., LE MEVEL, J. C., CHATENET, D., TOSTIVINT, H., FOURNIER, A., TONON, M. C., PELLETIER, G., MICHAEL CONLON, J. & LEPRINCE, J. (2010)
Urotensin II, from fish to human .
Annals of the New York Academy of Sciences , 1200, 53-66
 

 

359. DOAN, N. D., BOURGAULT, S., DEJDA, A., LÉTOURNEAU, M., DETHEUX, M., VAUDRY, D., VAUDRY, H., CHATENET, D. & FOURNIER, A. (2010)
Design and in vitro characterization of PAC1/VPAC1-selective agonists with potent neuroprotective effects .
Biochemical Pharmacology , Article in Press,
 

 

358. DEJDA, A., CHAN, P., SEABORN, T., COQUET, L., JOUENNE, T., FOURNIER, A., VAUDRY, H. & VAUDRY, D. (2010)
Involvement of stathmin 1 in the neurotrophic effects of PACAP in PC12 cells .
Journal of Neurochemistry , 114, 5, 1498-510
 

 

357. ALLAIS, A., BUREL, D., ROY, V., ARTHAUD, S., GALAS, L., ISAAC, E. R., DESFEUX, A., PARENT, B., FOURNIER, A., CHAPILLON, P., SHERWOOD, N. M., VAUDRY, H. & GONZALEZ, B. J. (2010)
Balanced effect of PACAP and FasL on granule cell death during cerebellar development: a morphological, functional and behavioural characterization .
Journal of Neurochemistry , 113, 2, 329-340
 

 

356. VAUDRY, D., FALLUEL-MOREL, A., BOURGAULT, S., BASILLE, M., BUREL, D., WURTZ, O., FOURNIER, A., CHOW, B. K. C., HASHIMOTO, H., GALAS, L. & VAUDRY, H. (2009)
Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 Years after the discovery .
Pharmacological Reviews , 61, 3, 283-357
 

 

355. MOUNIEN, L., DO REGO, J. C., BIZET, P., BOUTELET, I., GOURCEROL, G., FOURNIER, A., BRABET, P., COSTENTIN, J., VAUDRY, H. & JÉGOU, S. (2009)
Pituitary adenylate cyclase-activating polypeptide inhibits food intake in mice through activation of the hypothalamic melanocortin system .
Neuropsychopharmacology , 34, 2, 424-435
 

 

354. LEFEBVRE, T., GONZALEZ, B. J., VAUDRY, D., DESRUES, L., FALLUEL-MOREL, A., AUBERT, N., FOURNIER, A., TONON, M. C., VAUDRY, H. & CASTEL, H. (2009)
Paradoxical effect of ethanol on potassium channel currents and cell survival in cerebellar granule neurons .
Journal of Neurochemistry , 110, 3, 976-989
 

 

353. JOLIVEL, V., BASILLE, M., AUBERT, N., DE JOUFFREY, S., ANCIAN, P., LE BIGOT, J. F., NOACK, P., MASSONNEAU, M., FOURNIER, A., VAUDRY, H., GONZALEZ, B. J. & VAUDRY, D. (2009)
Distribution and functional characterization of pituitary adenylate cyclase-activating polypeptide receptors in the brain of non-human primates .
Neuroscience , 160, 2, 434-451
 

 

352. HONG, Y., LIU, Y., CHABOT, J. G., FOURNIER, A. & QUIRION, R. (2009)
Upregulation of adrenomedullin in the spinal cord and dorsal root ganglia in the early phase of CFA-induced inflammation in rats .
Pain , 146, 1-2, 105-113
 

 

351. FU, Y., LÉTOURNEAU, M., NGUYEN, Q. T., CHATENET, D., DUPUIS, J. & FOURNIER, A. (2009)
Characterization of the adrenomedullin receptor acting as the target of a new radiopharmaceutical biomolecule for lung imaging .
European Journal of Pharmacology , 617, 1-3, 118-123
 

 

350. DUPUIS, J., HAREL, F., FU, Y., QUANG, T. N., LÉTOURNEAU, M., PRÉFONTAINE, A. & FOURNIER, A. (2009)
Molecular imaging of monocrotaline-induced pulmonary vascular disease with radiolabeled linear adrenomedullin .
Journal of Nuclear Medicine , 50, 7, 1110-1115
 

 

349. CHATENET, D., LÉTOURNEAU, M. & FOURNIER, A. (2009)
Design, Synthesis and Biological Activities of New Urotensin Ii-Related Peptides (Urp) .
Proceedings of the Twenty-First American Peptide Symposium June 7-12, 2009, Bloomington, IN, U.S.A. , 133-134
 

 

348. BOURGAULT, S., VAUDRY, D., SÉGALAS-MILAZZO, I., GUILHAUDIS, L., COUVINEAU, A., LABURTHE, M., VAUDRY, H. & FOURNIER, A. (2009)
Molecular and conformational determinants of pituitary adenylate cyclase-activating polypeptide (PACAP) for activation of the PAC1 receptor .
Journal of Medicinal Chemistry , 52, 10, 3308-3316
 

 

347. BOURGAULT, S., VAUDRY, D., DEJDA, A., DOAN, N. D., VAUDRY, H. & FOURNIER, A. (2009)
Pituitary adenylate cyclase-activating polypeptide: focus on structure-activity relationships of a neuroprotective Peptide .
Current Medicinal Chemistry , 16, 33, 4462-80
 

 

346. ZHOKHOV, S. S., DESFEUX, A., AUBERT, N., FALLUEL-MOREL, A., FOURNIER, A., LAUDENBACH, V., VAUDRY, H. & GONZALEZ, B. J. (2008)
Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage .
Cell Death and Differentiation , 15, 6, 1042-1053
 

 

345. PARAT, M., MCNICOLL, N., WILKES, B., FOURNIER, A. & DE LÉAN, A. (2008)
Role of extracellular domain dimerization in agonist-induced activation of natriuretic peptide receptor A .
Molecular Pharmacology , 73, 2, 431-440
 

 

344. LEPRINCE, J., CHATENET, D., DUBESSY, C., FOURNIER, A., PFEIFFER, B., SCALBERT, E., RENARD, P., PACAUD, P., OULYADI, H., SÉGALAS-MILAZZO, I., GUILHAUDIS, L., DAVOUST, D., TONON, M. C. & VAUDRY, H. (2008)
Structure-activity relationships of urotensin II and URP .
Peptides , 29, 5, 658-673
 

 

343. HAREL, F., FU, Y., NGUYEN, Q. T., LÉTOURNEAU, M., PERRAULT, L. P., CARON, A., FOURNIER, A. & DUPUIS, J. (2008)
Use of adrenomedullin derivatives for molecular imaging of pulmonary circulation .
Journal of Nuclear Medicine , 49, 11, 1869-1874
 

 

342. GRUMOLATO, L., GHZILI, H., MONTERO-HADJADJE, M., GASMAN, S., LESAGE, J., TANGUY, Y., GALAS, L., AIT-ALI, D., LEPRINCE, J., GUÉRINEAU, N. C., ELKAHLOUN, A. G., FOURNIER, A., VIEAU, D., VAUDRY, H. & ANOUAR, Y. (2008)
Selenoprotein T is a PACAP-regulated gene involved in intracellular Ca 2+ mobilization and neuroendocrine secretion .
Faseb Journal , 22, 6, 1756-1768
 

 

341. DOAN, N. D., BOURGAULT, S., LÉTOURNEAU, M. & FOURNIER, A. (2008)
Effectiveness of the Suzuki - Miyaura cross-coupling reaction for solid-phase peptide modification .
Journal of Combinatorial Chemistry , 10, 1, 44-51
 

 

340. DEJDA, A., JOLIVEL, V., BOURGAULT, S., SEABORN, T., FOURNIER, A., VAUDRY, H. & VAUDRY, D. (2008)
Inhibitory effect of PACAP on caspase activity in neuronal apoptosis: A better understanding towards therapeutic applications in neurodegenerative diseases .
Journal of Molecular Neuroscience , 36, 1-3, 26-37
 

 

339. BOURGAULT, S., VAUDRY, D., GUILHAUDIS, L., RAOULT, É., COUVINEAU, A., LABURTHE, M., SÉGALAS-MILAZZO, I., VAUDRY, H. & FOURNIER, A. (2008)
Biological and structural analysis of truncated analogs of PACAP27 .
Journal of Molecular Neuroscience , 36, 1-3, 260-269
 

 

338. BOURGAULT, S., VAUDRY, D., BOTIA, B., COUVINEAU, A., LABURTHE, M., VAUDRY, H. & FOURNIER, A. (2008)
Novel stable PACAP analogs with potent activity towards the PAC1 receptor .
Peptides , 29, 6, 919-932
 

 

337. BOTIA, B., SEYER, D., RAVNI, A., BÉNARD, M., FALLUEL-MOREL, A., COSETTE, P., JOUENNE, T., FOURNIER, A., VAUDRY, H., GONZALEZ, B. J. & VAUDRY, D. (2008)
Peroxiredoxin 2 is involved in the neuroprotective effects of PACAP in cultured cerebellar granule neurons .
Journal of Molecular Neuroscience , 36, 1-3, 61-72
 

 

336. BOIVIN, S., SÉGALAS-MILAZZO, I., GUILHAUDIS, L., OULYADI, H., FOURNIER, A. & DAVOUST, D. (2008)
Solution structure of urotensin-II receptor extracellular loop III and characterization of its interaction with urotensin-II. .
Peptides , 29, 5, 700-710
 

 

335. AUBIN, J., LÉTOURNEAU, M., FRANCOEUR, E., BURGEON, E. & FOURNIER, A. (2008)
Identification of ETA and ETB binding domains using ET-derived photoprobes .
Biochimie , 90, 6, 918-929
 

 

334. AUBERT, N., VAUDRY, D., FALLUEL-MOREL, A., DESFEUX, A., FISCH, C., ANCIAN, P., DE JOUFFREY, S., LE BIGOT, J. F., COUVINEAU, A., LABURTHE, M., FOURNIER, A., LAUDENBACH, V., VAUDRY, H. & GONZALEZ, B. J. (2008)
PACAP prevents toxicity induced by cisplatin in rat and primate neurons but not in proliferating ovary cells: Involvement of the mitochondrial apoptotic pathway .
Neurobiology of Disease , 32, 1, 66-80
 

 

333. VIAU, M., LÉTOURNEAU, M., SIROIS-DESLONGCHAMPS, A., BOULANGER, Y. & FOURNIER, A. (2007)
Study of solid-phase synthesis and purification strategies for the preparation of polyglutamine peptides .
Biopolymers , 88, 5, 754-763
 

 

332. OKADA, R., YAMAMOTO, K., ITO, Y., MOCHIDA, H., TONON, M. C., FOURNIER, A., LEPRINCE, J., VAUDRY, H. & KIKUYAMA, S. (2007)
VIP and PACAP stimulate TSH release from the bullfrog pituitary .
Peptides , 28, 9, 1784-1789
 

 

331. MASMOUDI-KOUKI, O., GANDOLFO, P., CASTEL, H., LEPRINCE, J., FOURNIER, A., DEJDA, A., VAUDRY, H. & TONON, M. C. (2007)
Role of PACAP and VIP in astroglial functions .
Peptides , 28, 9, 1753-1760
 

 

330. LEGROS, E., TIRAPELLI, C. R., CARRIER, E., BROCHU, I., FOURNIER, A. & D'ORLÉANS-JUSTE, P. (2007)
Characterization of the non-adrenergic/noncholinergic response to perivascular nerve stimulation in the double-perfused mesenteric bed of the mouse .
British Journal of Pharmacology , 152, 7, 1049-1059
 

 

329. FALLUEL-MOREL, A., CHAFAI, M., VAUDRY, D., BASILLE, M., CAZILLIS, M., AUBERT, N., LOUISET, E., DEJOUFFREY, S., LE BIGOT, J. F., FOURNIER, A., GRESSENS, P., ROSTÈNE, W., VAUDRY, H. & GONZALES, B. (2007)
The neuropeptide pituitary adenylate cyclase-activating polypeptide exerts anti-apoptotic and differentiating effects during neurogenesis: Focus on cerebellar granule neurones and embryonic stem cells .
Journal of Neuroendocrinology , 19, 5, 321-327
 

 

328. DUMONT, Y., MOYSE, E., FOURNIER, A. & QUIRION, R. (2007)
Distribution of peripherally injected peptide YY ([125I] PYY (3-36)) and pancreatic polypeptide ([125I] hPP) in the CNS: enrichment in the area postrema .
Journal of Molecular Neuroscience , 33, 3, 294-304
 

 

327. DE MONTGOLFIER, B., DUFRESNE, J., LÉTOURNEAU, M., NAGLER, J. J., FOURNIER, A., AUDET, C. & CYR, D. G. (2007)
The expression of multiple connexins throughout spermatogenesis in the rainbow trout testis suggests a role for complex intercellular communication .
Biology of Reproduction , 76, 1, 2-8
 

 

326. BOURGAULT, S., LÉTOURNEAU, M. & FOURNIER, A. (2007)
Development of photolabile caged analogs of endothelin-1 .
Peptides , 28, 5, 1074-1082
 

 

325. BOTIA, B., BASILLE, M., ALLAIS, A., RAOULT, E., FALLUEL-MOREL, A., GALAS, L., JOLIVEL, V., WURTZ, O., KOMURO, H., FOURNIER, A., VAUDRY, H., BUREL, D., GONZALEZ, B. J. & VAUDRY, D. (2007)
Neurotrophic effects of PACAP in the cerebellar cortex .
Peptides , 28, 9, 1746-52
 

 

324. AUBERT, N., BASILLE, M., FALLUEL-MOREL, A., VAUDRY, D., BUCHARLES, C., JOLIVEL, V., FISCH, C., DE JOUFFREY, S., LE BIGOT, J. F., FOURNIER, A., VAUDRY, H. & GONZALEZ, B. J. (2007)
Molecular, cellular, and functional characterizations of pituitary adenylate cyclase-activating polypeptide and its receptors in the cerebellum of new and old world monkeys .
Journal of Comparative Neurology , 504, 4, 427-439
 

 

323. VAUDRY, D., RAVNI, A., WURTZ, O., BÉNARD, M., BOTIA, B., JOLIVEL, V., FOURNIER, A., GONZALEZ, B. J. & VAUDRY, H. (2006)
Effects of PACAP in the local regulation of endocrine glands. .
Handbook of Biologically Active Peptides. London, Academic Press.

 

322. VALLARINO, M., BRUZZONE, F., MATHIEU, M., CHARTREL, N., VIEAU, D., CIARLO, M., FOURNIER, A. & VAUDRY, H. (2006)
Ontogeny of the somatostatin variant [Pro2,Met 13]somatostatin-14 in the brain, pituitary, and sensory organs of the frog Rana esculenta .
Journal of Comparative Neurology , 497, 5, 717-733
 

 

321. TAKHSHID, M. A., POYNER, D. R., CHABOT, J. G., FOURNIER, A., MA, W. Y., ZHENG, W. H., OWJI, A. A. & QUIRION, R. (2006)
Characterization and effects on cAMP accumulation of adrenomedullin and calcitonin gene-related peptide (CGRP) receptors in dissociated rat spinal cord cell culture .
British Journal of Pharmacology , 148, 4, 459-468
 

 

320. RAVNI, A., BOURGAULT, S., LEBON, A., CHAN, P., GALAS, L., FOURNIER, A., VAUDRY, H., GONZALEZ, B., EIDEN, L. E. & VAUDRY, D. (2006)
The neurotrophic effects of PACAP in PC12 cells: Control by multiple transduction pathways .
Journal of Neurochemistry , 98, 2, 321-329
 

 

319. OKADA, R., YAMAMOTO, K., ITO, Y., CHARTREL, N., LEPRINCE, J., FOURNIER, A., VAUDRY, H. & KIKUYAMA, S. (2006)
Effects of pituitary adenylate cyclase-activating polypeptide, vasoactive intestinal polypeptide, and somatostatin on the release of thyrotropin from the bullfrog pituitary .
Vip, Pacap, and Related Peptides: From Gene to Therapy , 1070, 474-480
 

 

318. MOUNIEN, L., BIZET, P., BOUTELET, I., GOURCEROL, G., FOURNIER, A., VAUDRY, H. & JÉGOU, S. (2006)
Pituitary adenylate cyclase-activating polypeptide directly modulates the activity of proopiomelanocortin neurons in the rat arcuate nucleus .
Neuroscience , 143, 1, 155-163
 

 

317. MONTERO-HADJADJE, M., DELARUE, C., FOURNIER, A., VAUDRY, H. & YON, L. (2006)
Involvement of the adenylyl cyclase/protein kinase A signaling pathway in the stimulatory effect of PACAP on frog adrenocortical cells .
Annals of the New York Academy of Sciences , 1070, 431-435
 

 

316. MASMOUDI-KOUKI, O., GANDOLFO, P., LEPRINCE, J., VAUDRY, D., PELLETIER, G., FOURNIER, A., VAUDRY, H. & TONON, M. C. (2006)
PACAP stimulates biosynthesis and release of endozepines from rat astrocytes .
Annals of the New York Academy of Sciences , 1070, 411-416
 

 

315. LEBON, A., SEYER, D., COSETTE, P., COQUET, L., JOUENNE, T., CHAN, P., LEPRINCE, J., FOURNIER, A., VAUDRY, H., GONZALEZ, B. J. & VAUDRY, D. (2006)
Identification of proteins regulated by PACAP in PC12 cells by 2D gel electrophoresis coupled to mass spectrometry .
Annals of the New York Academy of Sciences , 1070, 380-387
 

 

314. GUILLEMOT, J., AÏT-ALI, D., TURQUIER, V., MONTERO-HADJADJE, M., FOURNIER, A., VAUDRY, H., ANOUAR, Y. & YON, L. (2006)
Involvement of multiple signaling pathways in PACAP-induced EM66 secretion from chromaffin cells .
Regulatory Peptides , 137, 1-2, 79-88
 

 

313. GUILLEMOT, J., AIT-ALI, D., TURQUIER, V., MONTERO-HADJADJE, M., FOURNIER, A., VAUDRY, H., ANOUAR, Y. & YON, L. (2006)
PACAP stimulates the release of the secretogranin II-derived peptide EM66 from chromaffin cells .
Annals of the New York Academy of Sciences , 1070, 309-312
 

 

312. FALLUEL-MOREL, A., VAUDRY, D., AUBERT, N., GALAS, L., BENARD, M., BASILLE, M., FONTAINE, M., FOURNIER, A., VAUDRY, H. & GONZALEZ, B. J. (2006)
PACAP and ceramides exert opposite effects on migration, neurite outgrowth, and cytoskeleton remodeling .
Annals of the New York Academy of Sciences , 1070, 265-270
 

 

311. CASTEL, H., VAUDRY, D., MEI, Y. A., LEFEBVRE, T., BASILLE, M., DESRUES, L., FOURNIER, A., VAUDRY, H., TONON, M. C. & GONZALEZ, B. J. (2006)
The delayed rectifier channel current IK plays a key role in the control of programmed cell death by PACAP and ethanol in cerebellar granule neurons .
Annals of the New York Academy of Sciences , 1070, 173-179
 

 

310. BOIVIN, S., GUILHAUDIS, L., SEGALAS-MILAZZO, I., OULYADI, H., DAVOUST, D. & FOURNIER, A. (2006)
NMR study of urotensin-II receptor structural domains .
29th European Peptide Symposium, Gdansk, Poland, September 3-8, 2006 , 120
 

 

309. BOIVIN, S., GUILHAUDIS, L., MILAZZO, I., OULYADI, H., DAVOUST, D. & FOURNIER, A. (2006)
Characterization of urotensin-II receptor structural domains involved in the recognition of U-II, URP, and urantide .
Biochemistry , 45, 19, 5993-6002
 

 

308. BASILLE, M., FALLUEL-MOREL, A., VAUDRY, D., AUBERT, N., FOURNIER, A., FRÉGER, P., GALLO-PAYET, N., VAUDRY, H. & GONZALEZ, B. (2006)
Ontogeny of PACAP receptors in the human cerebellum: Perspectives of therapeutic applications .
Regulatory Peptides , 137, 1-2, 27-33
 

 

307. BASILLE, M., CARTIER, D., VAUDRY, D., LIHRMANN, I., FOURNIER, A., FREGER, P., GALLO-PAYET, N., VAUDRY, H. & GONZALEZ, B. (2006)
Localization and characterization of pituitary adenylate cyclase-activating polypeptide receptors in the human cerebellum during development .
Journal of Comparative Neurology , 496, 4, 468-478
 

 

306. AUBERT, N., FALLUEL-MOREL, A., VAUDRY, D., XIFRO, X., RODRIGUEZ-ALVAREZ, J., FISCH, C., DE JOUFFREY, S., LEBIGOT, J. F., FOURNIER, A., VAUDRY, H. & GONZALEZ, B. J. (2006)
PACAP and C2-ceramide generate different AP-1 complexes through a MAP-kinase-dependent pathway: involvement of c-Fos in PACAP-induced Bcl-2 expression .
Journal of Neurochemistry , 99, 4, 1237-1250
 

 

305. THUAU, R., GUILHAUDIS, L., SÉGALAS-MILAZZO, I., CHARTREL, N., OULYADI, H., BOIVIN, S., FOURNIER, A., LEPRINCE, M., DAVOUST, D. & VAUDRY, H. (2005)
Structural studies on 26RFa, a novel human RFamide-related peptide with orexigenic activity .
Peptides , 26, 5, 779-789
 

 

304. TESSIER, S., BOIVIN, S., AUBIN, J., LAMPRON, P., DETHEUX, M. & FOURNIER, A. (2005)
Transmembrane domain V of the endothelin-A receptor is a binding domain of ETA-selective TTA-386-derived photoprobes .
Biochemistry , 44, 21, 7844-7854
 

 

303. REDROBE, J. P., DUMONT, Y., FOURNIER, A., BAKER, G. B. & QUIRION, R. (2005)
Role of serotonin (5-HT) in the antidepressant-like properties of neuropeptide Y (NPY) in the mouse forced swim test .
Peptides , 26, 8, 1394-1400
 

 

302. MIGNEAULT, A., SAUVAGEAU, S., VILLENEUVE, L., THORIN, E., FOURNIER, A., LEBLANC, N. & DUPUIS, J. (2005)
Chronically elevated endothelin levels reduce pulmonary vascular reactivity to nitric oxide .
American Journal of Respiratory and Critical Care Medicine , 171, 5, 506-513
 

 

301. LANGLOIS, C., LÉTOURNEAU, M., TURCOTTE, K., DETHEUX, M. & FOURNIER, A. (2005)
PTHrP fragments 1-16 and 1-23 do not bind to either the ETA or the ETB endothelin receptors .
Peptides , 26, 8, 1436-1440
 

 

300. JOSSART, C., COUPAL, M., MCNICOLL, N., FOURNIER, A., WILKES, B. C. & DE LÉAN, A. (2005)
Photolabeling study of the ligand binding domain of natriuretic peptide receptor A: Development of a model .
Biochemistry , 44, 7, 2397-2408
 

 

299. HADDAD, S., D’ELIA, M., BERNIER, J., FOURNIER, A. & CYR, D. G. (2005)
Applications of genomics in immunotoxicology .
Investigative Immunotoxicology , 363-385
 

 

298. FALLUEL-MOREL, A., VAUDRY, D., AUBERT, N., GALAS, L., BENARD, M., BASILLE, M., FONTAINE, M., FOURNIER, A., VAUDRY, H. & GONZALEZ, B. J. (2005)
Effets du PACAP et du C2-céramide sur la motilité des neurones en grain du cervelet : rien ne sert de courir, il faut partir à point .
M S-Medecine Sciences , 21, 8-9, 696-698
 

 

297. FALLUEL-MOREL, A., VAUDRY, D., AUBERT, N., GALAS, L., BENARD, M., BASILLE, M., FONTAINE, M., FOURNIER, A., VAUDRY, H. & GONZALEZ, B. J. (2005)
Pituitary adenylate cyclase-activating polypeptide prevents the effects of ceramides on migration, neurite outgrowth, and cytoskeleton remodeling .
Proceedings of the National Academy of Sciences of the United States of America , 102, 7, 2637-2642
 

 

296. DUMONT, Y., MOYSE, E., FOURNIER, A. & QUIRION, R. (2005)
Evidence for the existence of an additional class of neuropeptide Y receptor sites in rat brain .
Journal of Pharmacology and Experimental Therapeutics , 315, 1, 99-108
 

 

295. DUMONT, Y., GAUDREAU, P., MAZZUFERI, M., LANGLOIS, D., CHABOT, J. G., FOURNIER, A., SIMONATO, M. & QUIRION, R. (2005)
BODIPY®-conjugated neuropeptide Y ligands: New fluorescent tools to tag Y1, Y2, Y4 and Y5 receptor subtypes .
British Journal of Pharmacology , 146, 8, 1069-1081
 

 

294. DESCHÊNES, J., DUPERE, U., MCNICOLL, N., L'HEUREUX, N., AUGER, F., FOURNIER, A. & DE LÉAN, A. (2005)
Development of a selective peptide antagonist for the human natriuretic peptide receptor-B .
Peptides , 26, 3, 517-524
 

 

293. DELARUE, C., JOUET, I. R., GRAS, M., GALAS, L., FOURNIER, A. & VAUDRY, H. (2005)
Activation of endothelin(A) receptors in frog adrenocortical cells stimulates both calcium mobilization from intracellular stores and calcium influx through L-type calcium channels .
Endocrinology , 146, 1, 119-129
 

 

292. BOURGAULT, S., LÉTOURNEAU, M. & FOURNIER, A. (2005)
Development and pharmacological characterization of "caged" urotensin II analogs .
Peptides , 26, 8, 1475-1480

 

Chaires, groupes et réseaux

 

Codirecteur du Laboratoire international Samuel de Champlain, mis sur pied dans le cadre d'un LIA supporté par l'Institut national de la santé et de la recherche médicale (INSERM) et de l'Institut national de la recherche scientifique (INRS). Les travaux focalisent  sur la pharmacologie et la biochimie des neuropeptides. Le codirecteur du côté français est le professeur Hubert Vaudry de l'Université de Rouen.

 

Fonction et biographie

 

Le Pr Alain Fournier a successivement obtenu à l'Université de Sherbrooke un baccalauréat en chimie-biochimie, une maîtrise en pharmacologie et un doctorat en chimie bioorganique. Après des études postdoctorales au Health Sciences Centre de l'Université de Calgary, puis au Roche Research Centre de Nutley, New Jersey, il est entré en fonction en 1987 à titre de professeur à l'INRS-Institut Armand-Frappier. Il a été successivement Chercheur-boursier Junior et Senior du Fonds de la recherche en santé du Québec, ainsi que Chercheur National de ce même organisme. Il a aussi été pendant plusieurs années professeur associé au Département de Pharmacologie de l’Université de Montréal ainsi qu’au Département de Pharmacologie de l’Université de Sherbrooke. De février 2006 à janvier 2008, il a été Directeur intérimaire du centre INRS - Institut Armand-Frappier, pour par la suite devenir le directeur en titre jusqu'en septembre 2010. Après son mandat de directeur de centre, il est devenu Directeur scientifique (vice-recteur enseignement et recherche) de l'INRS. Il a occupé ce poste jusqu'en mars 2013. Il est ensuite redevenu professeur-chercheur et il poursuit ses activités de recherche en chimie médicinale et pharmacologie. Récemment, il est devenu professeur honoraire de l'INRS après avoir pris sa retraite (décembre 2016).
 
Avec sa formation pluridisciplinaire en chimie, pharmacologie et biochimie, le Pr Fournier oeuvre dans des champs de recherche exigeant la mise au point de méthodes de synthèse d'hormones polypeptidiques, leur évaluation structurale au moyen d'estimations théoriques et de techniques spectroscopiques, ainsi que la mesure de leurs propriétés pharmacologiques et biochimiques. Son parcours lui a permis de recevoir divers prix et honneurs dont le Prix Adrien-Pouliot de l'ACFAS (2012) et le Prix Planète INRS (2015).

 

Activités scientifiques

 

1. Préparation of polysulfated peptides as cholecystokinin-8 analogs

 

Brevets et brevets provisoires

 

X-​(R)​n-​Tyr(SO3H)​-​R1-​R2-​R3-​R4-​R5-​MePhe-​Y [X = COR6, CO2R6, CO(CH2)​mMe, COCO2R7, CO(CH2)​mCO2R8; R = Asp, Arg; R1 = Met, Nle, Leu, null; R2 = Gly, Ala, D-​Ala, β-​Ala; R3 = Trp, Trp(CHO)​; R4 = Met, Nle, Nva, Pro; R5 = Thr(SO3H)​, Ser(SO3H)​, Hyp(SO3H)​; R6, R8, R9, R10 = H, alkyl; or R7 = R8 = H, (halo)​alkyl; Y = OR8, NR9R10; n = 0, 1; m = 1-​14] are prepd. by the solid phase method using benzotriazol-​1-​yloxy-​tris(dimethylamino)​phosphonium hexafluorophosphate (I) as a coupling reagent; the OH groups of hydroxyamino acids are not protected and side reactions during peptide synthesis are minimized by using 3 equiv of I and 3 equiv of N-​(tert-​butoxycarbonyl)​hydroxyamino acid in the coupling step.  Ac-​Tyr(SO3H)​-​Met-​Gly-​Trp-​Met-​Thr(SO3H)​-​Phe-​NH2 was prepd. using BOC-​Phe-​PAM resin (BOC = CO2CMe3)​, wherein the fully assembled peptide-​resin was sulfated by SO3·pyridine complex or pyridinium acetyl sulfate in pyridine.  Also prepd. was Ac-​Tyr(SO3H)​-​Nle-​Gly-​Trp-​Nle-​Thr(SO3H)​-​MePhe-​NH2.

 

Patent No :

 

US 4965343

Date : Oct 23, 1990

   Application No : US 1988-149261 Date : Jan 28, 1988

Priority Application: US 1988-149261   Date: Jan 28, 1988

 

2. Labelled adrenomedullin derivatives and their use for imaging ant therapy

by : Dupuis, Jocelyn; Fournier, Alain

Assignee: Institut de Cardiologie de Montreal, Can.

 

The present invention relates to an adrenomedullin derivative including an adrenomedullin peptide chelated with at least one active agent.  Examples of active agents include a paramagnetic element, a radioactive element and a fibrinolytic agent, among others.  Paramagnetic agents have a distribution that is relatively easily shown through Magnetic Resonnance Imaging (MRI)​.  Radioactive agents have applications in imaging and delivery of radiations, depending on the specific element included in the active agent.  Delivery of fibrinolytic agents mainly to a specific organ, such as for example to the lungs, allows to substantially improve the specificity and efficacy of thrombolytic therapy by allowing local delivery of the fibrinolytic agent, thereby reducing the risks of major bleeding in the therapy of the organ.  If the organ is the lungs, a non-​limiting example of pathol. treatable with the fibrinolytic is pulmonary embolus.

 

Patent No.

 

Kind

Language

Date

Application No.

Date

WO 2005116065

 

A1

 

Dec 8, 2005

WO 2005-CA791

May 24, 2005

CA 2567478

 

A1

 

Dec 8, 2005

CA 2005-2567478

May 24, 2005

CA 2567478

 

C

 

Apr 1, 2014

 

 

EP 1749026

 

A1

 

Feb 7, 2007

EP 2005-748704

May 24, 2005

EP 1749026

 

B1

English

Nov 23, 2011

 

 

AT 534664

 

T

 

Dec 15, 2011

AT 2005-748704

May 24, 2005

US 20080274050

 

A1

 

Nov 6, 2008

US 2006-597315

Nov 21, 2006

US 8703098

 

B2

English

Apr 22, 2014

 

 

US 20090028790

 

A1

English

Jan 29, 2009

US 2008-149989

May 12, 2008

US 8475764

 

B2

English

Jul 2, 2013

 

 

US 20120082619

 

A1

English

Apr 5, 2012

US 2011-13067914

Jul 7, 2011

 

Priority Application

US 2004-60573334

P

May 24, 2004

WO 2005-CA791

W

May 24, 2005

US 2007-60924393

P

May 11, 2007

US 2008-149989

A1

May 12, 2008

 

2. Labelled adrenomedullin derivatives and their use for imaging ant therapy

by : Dupuis, Jocelyn; Fournier, Alain

Assignee: Institut de Cardiologie de Montreal, Can.


The present invention relates to an adrenomedullin derivative including an adrenomedullin peptide, or a fragment thereof chelated or otherwise bound to at least one active agent.  Examples of active agents include a paramagnetic element, a radioactive element and a fibrinolytic agent, among others.  Paramagnetic agents have a distribution that is relatively easily shown through Magnetic Resonance Imaging (MRI)​. Radioactive agents have applications in imaging and delivery of radiations, depending on the specific element included in the active agent.  Delivery of fibrinolytic agents mainly to a specific organ, such as for example to the lungs, allows to substantially improve the specificity and efficacy of thrombolytic therapy by allowing local delivery of the fibrinolytic agent, thereby reducing the risks of major bleeding in the therapy of the organ.  If the organ is the lungs, a non-​limiting example of pathol. treatable with the fibrinolytic agent is pulmonary embolus.

 

Patent No.

 

Kind

Language

Date

Application No.

      Date

WO 2008138141

 

A1

 

Nov 20, 2008

WO 2008-CA934

May 12, 2008

CA 2686760

 

A1

 

Nov 20, 2008

CA 2008-2686760

May 12, 2008

EP 2155781

 

A1

 

Feb 24, 2010

EP 2008-757094

May 12, 2008

EP 2155781

 

B1

English

Mar 13, 2013

 

 

 

 

 

Priority Application

US 2007-60924393

P

May 11, 2007

WO 2008-CA934

W

May 12, 2008

 

4. Labelled adrenomedullin derivatives and their use for imaging ant therapy

by : Dupuis, Jocelyn; Fournier, Alain

 

Assignee: Institut de Cardiologie de Montreal, Can.; Institut National de la Recherche Scientifique

 

The present invention relates to an adrenomedullin deriv. including an adrenomedullin peptide, or a fragment thereof chelated or otherwise bound to at least one active agent.  Examples of active agents include a paramagnetic element, a radioactive element and a fibrinolytic agent, among others.  Paramagnetic agents have a distribution that is relatively easily shown through Magnetic Resonance Imaging (MRI)​.  Radioactive agents have applications in imaging and delivery of radiations, depending on the specific element included in the active agent.  Delivery of fibrinolytic agents mainly to a specific organ, such as for example to the lungs, allows to substantially improve the specificity and efficacy of thrombolytic therapy by allowing local delivery of the fibrinolytic agent, thereby reducing the risks of major bleeding in the therapy of the organ.  If the organ is the lungs, a non-​limiting example of pathol. treatable with the fibrinolytic agent is pulmonary embolus.

 

 

Patent No.

 

Kind

Language

Date

Application No.

Date

US 20090028790

 

A1

 

Jan 29, 2009

US 2008-149989

May 12, 2008

US 8475764

 

B2

English

Jul 2, 2013

 

 

WO 2005116065

 

A1

English

Dec 8, 2005

WO 2005-CA791

May 24, 2005

US 20120082619

 

A1

English

Apr 5, 2012

US 2011-13067914

Jul 7, 2011

 

Priority Application

 

US 2004-60573334

P

May 24, 2004

 

WO 2005-CA791

A2

May 24, 2005

 

US 2007-60924393

P

May 11, 2007

 

US 2008-149989

A1

May 12, 2008

 

 

 

5. Novel agonists and antagonists of the urotensinergic system and their cardiovascular effects

by : Chatenet, David; Létourneau, Myriam; Fournier, Alain

Assignee: Institut National de la Recherche Scientifique, Can.

 

Novel urotensin II receptor (UT) agonists and antagonists are described herein.  More specifically, novel derivs. of urotensin II-​related peptide (URP) are described herein.  In an embodiment, the present disclosure relates to a urotensinergic agent or a pharmaceutical acceptable salt thereof having the formula: Ala-​Cys-​Phe-​X-​Lys-​Tyr-​Cys-​Val wherein X is an L-​or D-​amino acid and sidechain conformationally restricted phenylalanines, or a phenylalanine analog.  In an embodiment, the present disclosure relates to a method for discriminating between specific biol. action mediated by UII and​/or URP comprising the steps of: (i) exposing aortic rings to a urotensinergic agent as disclosed herein; (ii) prepg. concn.-​response curves to UII or URP; and (ii) evaluating the effect of the urotensinergic agent on aortic ring contraction induced by either UII or URP.  In a specific embodiment, the present disclosure relates to a biphenylalanine urotensin II-​related peptide ([Bip4]​URP i.e., urocontrin)​.

 

Patent No.

 

Kind

Language

Date

Application No.

Date

 

WO 2012149644

 

A1

 

Nov 8, 2012

WO 2012-CA421

May 3, 2012

CA 2832464

 

A1

 

Nov 8, 2012

CA 2012-2832464

May 3, 2012

AU 2012250462

 

A1

 

Nov 7, 2013

AU 2012-250462

May 3, 2012

 

EP 2729184

 

A1

 

May 14, 2014

EP 2012-779758

May 3, 2012

 

JP 2014518854

 

T

Japanese

Aug 7, 2014

JP 2014-508657

May 3, 2012

 

US 2014011387

 

A1

English

Apr 24, 2014

US 2014-14114757

Jan 9, 2014

 

         

 

Priority Application

 

US 2011-61481985

P

May 3, 2011

WO 2012-CA421

W

May 3, 2012

    

 

 

 

 

 

 

English

 

Research Interest

Peptides are molecules exhibiting various biological functions. They can act as hormones, growth factors, cellular signals, antibiotics,  neurotransmitters, neuromodulators, etc. Their wide spectrum of activity, their specificity and their potency make peptides among the most important biological agents known. A better knowledge of the mode of action of peptides, at the molecular level, is an essential step in the identification of adequate probes for the development and functioning of living organisms, as well as for the design of peptide derivatives or peptidomimetics potentially useful as pharmacological tools or therapeutic compounds.

Our studies focus on peptide families characterized by their exceptional properties on the nervous, endocrine and cardio-vascular systems (for instance, the pituitary adenylate cyclase-activating polypeptide, an endogenous molecule with potent cardioactive and neuroprotective activities). We aim at a better understanding of the biological functions of various peptides in normal physiological states and in acute or chronic physiopathologies.  Furthermore, the peptide compounds of our research program are used as models for pinpointing basic structural and biological features evaluated by means of spectroscopic, theoretical and pharmacological techniques. Thus, synthetic derivatives with subtle chemical modifications are assembled and their biological characteristics are determined in order to define precisely the structural parameters of the molecule. This approach is used to establish the correlation between the spatial organization of peptides and their biological properties. Concurrently, the identification of the amino acids and more precisely, the chemical groups of the molecule involved in the binding process of the peptide to the cellular receptor, guides our studies towards the design of new synthetic substances characterized by a structural arrangement respecting the receptor topography.

These peptidomimetics are able to reproduce the biological effects of the parent-molecule. They are therefore valuable tools for the characterization of physiological and pathological phenomena.

 

Biography

Dr. Alain Fournier received, from the Université de Sherbrooke, a B.Sc. degree in chemistry-biochemistry, a M. Sc. degree in pharmacology, and a Ph. D. degree in bio-organic chemistry. After post-doctoral studies at the Health Sciences Centre of the University of Calgary and the Roche Research Centre in Nutley, New Jersey, he has become in 1987 professor at INRS-Institut Armand-Frappier. He was successively Chercheur-boursier Junior and Senior from the Fonds de la recherche en santé du Québec, as well as Chercheur National from this organization. He was also for many years an affiliated professor at the Department of Pharmacology of the Faculty of Medicine of the Université de Sherbrooke, and at the Department of Pharmacology of the Faculty of Medicine of the Université de Montréal.

From February 2006 to January 2008, he was Interim Director of the Centre INRS - Institut Armand-Frappier and afterwards, he became the Director of the centre until September 2010. Then, he became Scientific Director  (vice-rector research and academic affairs) of INRS until March 2013. He then returned as a full professor in medicinal chemistry and pharmacology. He became Honorary Professor at INRS after his retirement on December 1st, 2016.

His multidisciplinary background in chemistry, pharmacology and biochemistry allows Dr. Fournier to carry out research programs involving peptide synthesis, structural analysis using theoretical calculations and spectroscopic techniques, as well as pharmacological and biochemical evaluations. His academic and scientific career was recognized through awards and honors such as the Prix Adrien-Pouliot from ACFAS (2012) and the Prix Planète from INRS (2015).

 

* Pr. Fournier does not recruit any additional graduate students or trainees