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LPEM

Laboratoire de Pharmacologie Expérimentale et Moléculaire

L'activité de recherche du laboratoire (LPEM) est basée sur la découverte, la caractérisation pharmacologique, l'ingénierie et l'évaluation préclinique in-vivo de peptides naturels et de phycotoxines pour développer des médicaments innovants et des kits de détection efficaces. 
Publié le 29 août 2022


RESPONSABLE

Denis Servent
01 69 08 52 02

denis.servent@cea.fr



MOYENS HUMAINS

​Muriel Amar, Maître de conférence, Université de Paris 
Romulo Aráoz, Chercheur CNRS
Évelyne Benoit, Chercheure CNRS
Nicolas Gilles, Chercheur CEA
Xavier Iturrioz, Chercheur Inserm
Mathilde Keck, Chercheur CEA
Pascal Kessler, Chercheur CEA
Jordi Molgó, Chercheur CNRS
Philippe Robin, Enseignant-chercheur, Université Paris-Saclay

Peggy Barbe, Technicienne CEA
Marion Chaigneau, Technicienne CEA
Nicolas Lamassiaude, Post-doctorant
Aurélie Antunes, Étudiante en thèse
Goran Stanajic Petrovic, Étudiant en thèse
Anne-Cécile Van Baelen, Étudiante en thèse



PUBLICATIONS

Araoz R, Barnes P, Sechet V, Delepierre M, Zinn-Justin S, Molgo J, Zakarian A, Hess P, Servent D. 2020. Cyclic imine toxins survey in coastal european shellfish samples: Bioaccumulation and mode of action of 28-O-palmitoyl ester of pinnatoxin-G. first report of portimine-A bioaccumulation. Harmful Algae  98, 101887. 10.1016/j.hal.2020.101887.

Araoz R, Ouanounou G, Iorga BI, Goudet A, Alili D, Amar M, Benoit E, Molgo J, Servent D. 2015. The neurotoxic effect of 13, 19-didesmethyl and 13-desmethyl spirolide C phycotoxins is mainly mediated by nicotinic rather than muscarinic acetylcholine receptors. Toxicol. Sci.  147, 156-167. 10.1093/toxsci/kfv119.

Benoit E, Couesnon A, Lindovsky J, Iorga BI, Araoz R, Servent D, Zakarian A, Molgo J. 2019. Synthetic Pinnatoxins A and G Reversibly Block Mouse Skeletal Neuromuscular Transmission In Vivo and In Vitro. Mar Drugs  17. 10.3390/md17050306.

Blanchet G, Alili D, Protte A, Upert G, Gilles N, Tepshi L, Stura EA, Mourier G, Servent D. 2017. Ancestral protein resurrection and engineering opportunities of the mamba aminergic toxins. Sci. Rep.  7, 2701. 10.1038/s41598-017-02953-0.

Ciolek J, Reinfrank H, Quinton L, Viengchareun S, Stura EA, Vera L, Sigismeau S, Mouillac B, Orcel H, Peigneur S, Tytgat J, Droctove L, Beau F, Nevoux J, Lombes M, Mourier G, De Pauw E, Servent D, Mendre C, Witzgall R, Gilles N. 2017. Green mamba peptide targets type-2 vasopressin receptor against polycystic kidney disease. Proc. Natl. Acad. Sci. U S A  114, 7154-7159. 10.1073/pnas.1620454114.

Droctove L, Lancien M, Tran VL, Susset M, Jego B, Theodoro F, Kessler P, Mourier G, Robin P, Diarra SS, Palea S, Flahault A, Chorfa A, Corbani M, Llorens-Cortes C, Mouillac B, Mendre C, Pruvost A, Servent D, Truillet C, Gilles N. 2020. A snake toxin as a theranostic agent for the type 2 vasopressin receptor. Theranostics  10, 11580-11594. 10.7150/thno.47485.

Fruchart-Gaillard C, Mourier G, Blanchet G, Vera L, Gilles N, Menez R, Marcon E, Stura EA, Servent D. 2012. Engineering of three-finger fold toxins creates ligands with original pharmacological profiles for muscarinic and adrenergic receptors. PLoS One  7, e39166. 10.1371/journal.pone.0039166

Goncalves TC, Benoit E, Kurz M, Lucarain L, Fouconnier S, Combemale S, Jaquillard L, Schombert B, Chambard JM, Boukaiba R, Hessler G, Bohme A, Bialy L, Hourcade S, Beroud R, De Waard M, Servent D, Partiseti M. 2019. From identification to functional characterization of cyriotoxin-1a, an antinociceptive toxin from the spider Cyriopagopus schioedtei. Br. J. Pharmacol.  176, 1298-1314. 10.1111/bph.14628.

Goncalves TC, Boukaiba R, Molgo J, Amar M, Partiseti M, Servent D, Benoit E. 2018. Direct evidence for high affinity blockade of NaV1.6 channel subtype by huwentoxin-IV spider peptide, using multiscale functional approaches. Neuropharmacology  133, 404-414. 10.1016/j.neuropharm.2018.02.016.

Molgo J, Schlumberger S, Sasaki M, Fuwa H, Louzao MC, Botana LM, Servent D, Benoit E. 2020. Gambierol Potently Increases Evoked Quantal Transmitter Release and Reverses Pre- and Post-Synaptic Blockade at Vertebrate Neuromuscular Junctions. Neuroscience  439, 106-116. 10.1016/j.neuroscience.2019.06.024.

Mourier G, Salinas M, Kessler P, Stura EA, Leblanc M, Tepshi L, Besson T, Diochot S, Baron A, Douguet D, Lingueglia E, Servent D. 2016. Mambalgin-1 Pain-relieving Peptide, Stepwise Solid-phase Synthesis, Crystal Structure, and Functional Domain for Acid-sensing Ion Channel 1a Inhibition. J. Biol. Chem.  291, 2616-29. 10.1074/jbc.M115.702373.

Petrel C, Hocking HG, Reynaud M, Upert G, Favreau P, Biass D, Paolini-Bertrand M, Peigneur S, Tytgat J, Gilles N, Hartley O, Boelens R, Stocklin R, Servent D. 2013. Identification, structural and pharmacological characterization of tau-CnVA, a conopeptide that selectively interacts with somatostatin sst3 receptor. Biochem. Pharmacol.  85, 1663-71. S0006-2952(13)00219-0 [pii]

Reynaud S, Ciolek J, Degueldre M, Saez NJ, Sequeira AF, Duhoo Y, Bras JLA, Meudal H, Cabo Diez M, Fernandez Pedrosa V, Verdenaud M, Boeri J, Pereira Ramos O, Ducancel F, Vanden Driessche M, Fourmy R, Violette A, Upert G, Mourier G, Beck-Sickinger AG, Morl K, Landon C, Fontes C, Minambres Herraiz R, Rodriguez de la Vega RC, Peigneur S, Tytgat J, Quinton L, De Pauw E, Vincentelli R, Servent D, Gilles N. 2020. A Venomics Approach Coupled to High-Throughput Toxin Production Strategies Identifies the First Venom-Derived Melanocortin Receptor Agonists. J Med Chem  63, 8250-8264. 10.1021/acs.jmedchem.0c00485.

Salinas M, Kessler P, Douguet D, Sarraf D, Tonali N, Thai R, Servent D, Lingueglia E. 2021. Mambalgin-1 pain-relieving peptide locks the hinge between alpha4 and alpha5 helices to inhibit rat acid-sensing ion channel 1a. Neuropharmacology  185, 108453. 10.1016/j.neuropharm.2021.108453.

Servent D, Malgorn C, Bernes M, Gil S, Simasotchi C, Herard AS, Delzescaux T, Thai R, Barbe P, Keck M, Beau F, Zakarian A, Dive V, Molgo J. 2021. First evidence that emerging pinnatoxin-G, a contaminant of shellfish, reaches the brain and crosses the placental barrier. Sci Total Environ  790, 148125. 10.1016/j.scitotenv.2021.148125.