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LPEM

LPEM: Experimental and Molecular Pharmacology Laboratory

​The laboratory (LPEM) research activity is based on the discovery, pharmacological characterization, engineering and in-vivo pre-clinical evaluation of natural peptides and phycotoxins to develop innovate drugs and efficient detection kits.  
Published on 12 August 2022


Lab LEADER

Denis Servent

01 69 08 52 02

denis.servent@cea.fr





Group Members:

Muriel Amar, Paris University Lecturer
Romulo Aráoz, CNRS Researcher
Evelyne Benoit, CNRS Researcher
Nicolas Gilles, CEA Researcher
Xavier Iturrioz, INSERM Researcher
Mathilde Keck, CEA Researcher
Pascal Kessler, CEA Researcher
Jordi Molgó, CNRS Researcher
Philippe Robin, Paris-Saclay University Lecturer
Peggy Barbe, CEA Technician
Marion Chaigneau, CEA Technician
Nicolas Lamassiaude, Postdoctoral Fellow
Aurélie Antunes, PhD student
Goran Stanajic Petrovic, PhD student
Anne-Cécile Van Baelen, PhD student

References

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.