Prof. Jean Sévigny

Department of Microbiology-Infectiology and Immunology

Université Laval, Canada


2010  Professor, Dept. of Microbiology-Infectiology and Immunology, Laval University
2009  Associate Professor, Dept. of Anatomy & Physiology, Laval University
2006  Assistant Professor, Dept. of Anatomy & Physiology, Laval University
1997  Ph.D., Biology, Sherbrooke University
1992  M.Sc., Microbiology, Sherbrooke University
1988  B.Sc., Biology (Biotechnology), Sherbrooke University

Publications (Selected)

  1. Enjyoji, K., J. Sévigny, Y. Lin, P.S. Frenette, P. D. Christie, J. Schulte am Esch II, M. Imai, J.M. Edelberg, H. Rayburn, M. Lech, D.L. Beeler, E. Csizmadia, D.D. Wagner, S.C. Robson & R.D. Rosenberg. (1999) Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation. Nat. Med.5(9): 1010-1017.
  2. Sévigny, J., S.C. Robson, E. Waelkens, E. Csizmadia, R.N. Smith & R. Lemmens. (2000) Identification and characterization of a novel hepatic canalicular ATP diphosphohydrolase. J. Biol. Chem.275(8): 5640-5647.
  3. Sévigny, J., C. Sundberg, N. Braun, O. Guckelberger, E. Csizmadia, I. Qawi, M. Imai, H. Zimmermann & S.C. Robson. (April 152002) Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation.Blood99(8) : 2801-2809.
  4. Dranoff, J. A., E. A. Kruglov, S.C. Robson, N. Braun, H. Zimmermann &J. Sévigny.(2002) Theecto-nucleoside triphosphate diphosphohydrolase NTPDase2/CD39L1 is expressed in a novel functional compartment within the liver.HepatologyNovember36(5): 1135-1144.
  5. Lavoie, E. G., F. Kukulski, S. A. Lévesque, J. Lecka&J. Sévigny.(2004) Cloning and characterization of mouse nucleoside triphosphate diphosphohydrolase-3.Biochem. Pharmacol.67(10): 1917-1926.
  6. Bigonnesse, F., S. A. Lévesque, F. Kukulski, J. Lecka, S.C. Robson, M.J.G. Fernandes&J. Sévigny.(2004) Cloning and characterization of mouse nucleoside triphosphate diphospho­hydrolase-8. Biochemistry43(18): 5511-5519.
  7. Kittel, A., J. Pelletier, F. Bigonnesse, O. Guckelberger, K. Kordás, N. Braun, S.C. Robson&J. Sévigny.(2004)Localization of nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and NTPDase2 in pancreas and salivary gland.J. Histochem. Cytochem.52(7): 861-871.
  8. Dranoff, J. A., E.A. Kruglov, J. Toure, N. Braun, H. Zimmermann, D. Jain, A.F. Knowles &J. Sévigny.(2004) Ectonucleotidase NTPDase2 is selectively down-regulated in biliary cirrhosis.Journal of Investigative Medicine52(7): 475-482.
  9. Kukulski, F., S. A. Lévesque, E.G. Lavoie, J. Lecka, F. Bigonnesse, A. F. Knowles, S.C. Robson, T. L. Kirley&J. Sévigny.(2005) Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8.Purinergic Signalling1(2): 193-204.
  10. Bartel, D. L., S.L. Sullivan, E. G. Lavoie, J. Sévigny& T.E. Finger.(2006) Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2) is the ecto-ATPase of type I cells in taste buds.J. Comp. Neurol.497(1): 1-12.
  11. Fausther, M., J. Lecka, F. Kukulski, S. A. Lévesque, J. Pelletier, H. Zimmermann, J. A. Dranoff&J. Sévigny.(2007) Cloning, purification, and identification of the liver canalicularecto-ATPase as NTPDase8. Am. J. Physiol.Gastrointest. Liver Physiol.292(3): G785-95.
  12. Kukulski, F., F. Ben Yebdri, J. Lefebvre, M. Warny, P. A. Tessier &J. Sévigny.(2007) Extracellular nucleotides mediate LPS-induced neutrophil migration in vitro and in vivo. J. Leukoc. Biol.81(5): 1269-75.
  13. Lévesque, S.A., E. G. Lavoie, J. Lecka, F. Bigonnesse&J. Sévigny.(2007) Specificity of the ecto-ATPase inhibitor ARL 67156 on major ecto-nucleotidases. Br. J. Pharmacol.152(1): 141-50.
  14. Munkonda, M. N., G. Kauffenstein, F. Kukulski, S. A. Lévesque, C. Legendre, J. Pelletier, E.G. Lavoie, J. Lecka&J. Sévigny.(2007) Inhibition of human and mouse plasma membrane bound NTPDases by P2 receptor antagonists. Biochem. Pharmacol.74: 1524-34.
  15. Munkonda, M.N., J. Pelletier, V.V. Ivanenkov, M. Fausther, A. Tremblay, B. Künzli, T.L. Kirley&J. Sévigny.(2009)Characterization of a mono­clonal antibody as the first specific inhibitor of human NTP diphosphohydrolase-3 - Partial characterization of the inhibitory epitope and potential applications.FEBS J.276:479-96.
  16. Martín-Satué, M., É.G. Lavoie, J. Pelletier, M. Fausther, E. Csizmadia, O. Guckelberger, S.C. Robson&J. Sévigny.(2009; epub 6 jn)Localization of plasma membrane bound NTPDases in the murine reproductive tract. Histochem. Cell. Biol.131(5):615-28.
  17. Kukulski, F., F. Ben Yebdri, J. Lecka, G. Kauffenstein,S.A. Lévesque, M. Martín-Satué&J. Sévigny.(2009) Extracellular ATP and P2 receptors are required for IL-8 to induce neutrophil migration. Cytokine46(2): 166-70.
  18. Ben Yebdri, F., F. Kukulski, A. Tremblay&J. Sévigny.(Oct2009)Concomitant activation of P2Y2and P2Y6receptors onmonocytes is required for TLR1/2-induced neutrophilmigration by regulating IL-8 secretion.Eur. J. Immunol.39(10):2885-94.
  19. Friedman, D.J., B.M. Künzli, Y.I. A-Rahim, J. Sévigny, P.O. Berberat, K.Enjyoji, E. Csizmadia, H.Friess& S.C. Robson.(2009)CD39 deletion exacerbates experimental murine colitis and human poly­morphisms increase susceptibility to inflammatory bowel disease.PNAS106(39): 16788-93.
  20. Kukulski, F., F. Ben Yebdri, F. Bahrami, S. A. Lévesque, M. Martín-Satué&J. Sévigny.(2010)TheP2 receptor antagonist PPADS abrogates LPS-induced neutrophil migration in the murine air pouch via inhibition of MIP-2 and KC production. Mol. Immunol.47(4): 833-9.
  21. Kauffenstein, G., A. Drouin, N. Thorin-Trescases, H. Bachelard, B. Robaye, P. D’Orléans-Juste, F. Marceau, É. Thorin&J. Sévigny.(2010) NTPDase1 (CD39) controls nucleotide-dependent vaso­constriction in mouse. Cardiovasc. Res.85(1): 204-13.
  22. Kukulski, F., F. Ben Yebdri, F. Bahrami, M. Fausther, A. Tremblay&J. Sévigny.(2010) Endothelial P2Y2receptor regulates LPS-induced neutrophil transendothelial migrationin vitro. Mol. Immunol.47(5): 991-9.
  23. Kauffenstein, G.,C. R. Fürstenau, P. D’Orléans-Juste&J. Sévigny.(2010). The ecto-nucleotidase NTPDase1 differentially regulates P2Y1and P2Y2receptor-dependent vaso­relaxation. Br. J. Pharmacol.159(3): 576-85.
  24. Eliahu, S., A. Martín-Gil, M.J. Perez de Lara, J. Pintor, J. Camden, G.A. Weisman, J. Lecka,J. Sévigny& B. Fischer. (2010) 2-MeS-β, γ-CCl2-ATP is a potent agent for reducing intraocular pressure.J. Med.Chem.53(8): 3305-19.
  25. Lévesque, S. A., F. Kukulski, K. Enjyoji, S.C. Robson&J. Sévigny.(2010) NTPDase1 governs P2X7-dependent functions in murine macrophages. Eur. J. Immunol.40(5): 1473-85.
  26. Martín-Satué, M., E.G. Lavoie, M. Fausther, J. Lecka, E. Aliagas, F. Kukulski&J. Sévigny.(2010) High expression and activity of ecto-5’-nucleotidase/CD73 in the male murine reproductive tract. Histochem. Cell. Biol.133(6): 659-68.
  27. Fausther, M., J. Pelletier, C. M. Ribeiro, J. Sévigny& M. Picher.(2010)Cystic fibrosis remodels the regulation of purinergic signaling by NTPDase1 and NTPDase3.Am. J. Physiology - Lung Cell. Mol. Physiol.298(6):L804-18.
  28. Lavoie, E. G., M. Fausther,G. Kauffenstein,F. Kukulski, B.M. Künzli, H. Friess&J. Sévigny.(2010) Identification of the ectonucleotidases expressed in mouse, rat and human Langerhans islets: Potential role of NTPDase3 ininsulin secretion. Am. J. Physiol. Endocrinol. Metab.299(4): E647-56.
  29. Lecka, J., M.anjitS.inghRana &J. Sévigny.(Nov2010; epub) Inhibition of vascular ectonucleotidase activities by the pro-drugs ticlopidine and clopidogrelfavours platelet aggregation. Br.J. Pharmacol.161(5): 1150-60.
  30. Eliahu, S., J. Lecka, G. Reiser, M. Haas,F. Bigonnesse, S. A. Lévesque, J. Pelletier&[Co senior authors J. Sévigny, B. Fischer]. (2010)Diadenosine-5',5''-(boranated)polyphosphonate analogues as selective Nucleotide Pyrophosphatase/Phos­pho­di­esterase(NPP)inhibitors.J. Med. Chem.53(24): 8485-97.
  31. Lavoie, E.G., B.D. Gulbransen, M. Martín-Satué, E. Aliagas, K. A. Sharkey &J. Sévigny.(2011)Ectonucleotidases in the digestive system:focus on NTPDase3 localization.Am. J. Physiol. Gastrointest. Liver Physiol.300(4): G608-20.
  32. Kukulski, F., F. Bahrami, F. Ben Yebdri, J. Lecka, M. Martín-Satué, S. A. Lévesque&J. Sévigny.(2011)NTPDase1 controls IL-8 production by human neutrophils. J. Immunol.187(2): 644-53.
  33. Fausther, M., J. Lecka, E. Soliman, G.Kauffenstein, J. Pelletier, N. Sheung, J.A. Dranoff&J. Sévigny.(2012) Co-expression of ecto-5'-nucleotidase/CD73 with specific NTPDases differentially regulates adenosine formation in the rat liver.Am. J. Physiol. Gastrointest. Liver Physiol.302: G447-59.
  34. Braganhol, E., R.F. Zanin, A. Bernardi, L.S. Bergamin, A.R. Cappellari, L.F. Campesato, F.B. Morrone, M.M. Campos, J.B. Calixto, M.I.A. Edelweiss, M.R. Wink,J. Sévigny, S.C. Robson & A.M.O. Battastini. (2012)Overexpression of CD39L1/NTPDase2 in gliomas promotes systemic inflammation and pulmonary injury.Purinergic Signalling8(2): 235-43.
  35. Lecka, J., I. Gillerman, M. Fausther, M. Salem, M.N. Munkonda, J.-P. Brosseau, C. Cadot, M. Martín-Satué, P. d'Orléans-Juste, É. Rousseau, D. Poirier, B. Künzli, B. Fischer&J. Sévigny.(2013) 8-BuS-ATP derivatives as specific NTPDase1 inhibitors.Br.J. Pharmacol.169(1): 179-96.
  36. Jenabian, M.-A., N, Seddiki, A, Yatim, M, Carriere, A, Hulin, M, Younas, E, Ghadimi, A, Kok, J.-P. Routy, A. Tremblay, J. Sévigny, J.-D. Lelievre&Y. Levy. (2013) Regulatory T cells negatively affect IL-2 production of effector T cells through CD39/Adenosine pathway in HIV infection.PLoS Pathogens9(4): e1003319.
  37. Lecka, J., G. Ben-David, S. Eliahu, J. Pelletier, J. Oscar Jr., P. Luyindula, B. Fischer, H. Senderowitz &J. Sévigny.(2013) Non-hydrolysable ATP analogs as selective inhibitors of human NPP1: A combined computational/experimental study.J. Med. Chem.56(21): 8308-20.
  38. Lecka, J., M. Fausther, M. Martín-Satué&J. Sévigny.(2014) CD39 may impact clopidrogrel pharmacodynamics. Austin J. Clin. Immunol. 1(1): 1-2.
  39. Nadel, Y., J. Lecka, Y. Gilad, G. Ben-David, D. Förster, G. Reiser, S. Kenigsberg, J. Camden, G.A. Weisman,[Co senior authorsH. Senderowitz, J. Sévigny, B. Fischer]. (2014) Highly potent and selective ectonucleotide pyrophosphatase/phosphodiesterase I inhibitors based on an adenosine5’-(α or γ)-thio-(α,β or β,γ)-methylenetriphosphate scaffold.J. Med. Chem. 57(11): 4677-91. doi: 10.1021/jm500196c.
  40. Bahrami, F., F. Kukulski, J. Lecka, A. Tremblay, J. Pelletier, L. Rockenbach&J. Sévigny.(2014) Purine metabolizing ectoenzymes control IL-8 production in human colon HT-29 cells. Mediators of Inflammation.vol. 2014, Article ID879895,10 pages. doi:10.1155/2014/879895.
  41. Rockenbach, L., E. Braganhol, F. Dietrich, F. Figueiró, M. Pugliese, M. I. A. Edelweiss, F. B. Morrone, J. Sévigny&A.M.O. Battastini. (2014) NTPDase3 and ecto-5’-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression. Purinergic Signalling.10(3): 421-30.
  42. Gillerman, I., J. Lecka, L. Simhaev, M.N. Munkonda, M. Fausther, M. Martín-Satué&[Co senior authors H. Senderowitz, J. Sévigny, B. Fischer]. (2014) 2-Hexylthio-β, γ-CH2-ATP is an effective and selective NTPDase2 inhibitor. J. Med. Chem.57(14): 5919-34. doi: 10.1021/jm401933c.
  43. Lecka, J., M. Fausther, Beat Künzli&J. Sévigny.(2014) Ticlopidine in its prodrug form is a selective inhibitor of human NTPDase1. Mediators of Inflammation. vol. 2014, Article ID547480, 8 pages. doi:10.1155/2014/547480.
  44. Kauffenstein, G., J. Pelletier, E. G. Lavoie, F. Kukulski, M. Martín-Satué, S. S. Dufresne, J. Frenette, C. Ribas Fürstenau, M.J. Sereda, B. Toutain, D. Henrion, R. Sullivan, C. Vial &J. Sévigny.(2014) Nucleoside triphosphate diphosphohydrolase-1 ectonucleotidase is required for normal vas deferens contraction and male fertility through maintaining P2X1 receptor function.J. Biol. Chem. 289(41): 28629-39.
  45. Braganhol, E., F. Kukulski, S. A. Lévesque, M. Fausther, E. G. Lavoie, A. Zanotto-Filho, L. S. Bergamin, J. Pelletier, F. Bahrami, F. Ben Yebdri, J.C. Moreira, A.M.O. Battastini&J. Sévigny.(2015) Nucleotide receptors control IL-8/CXCL8 and MCP-1/CCL2 secretions as well as proliferation in human glioma cells. Biochim. Biophys. Acta-Molecular Basis of Disease. 1852(1): 120-30. doi: 10.1016/j.bbadis.2014.10.014.

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Last Updated: July 7, 20115.

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