Mission/History
  Director
 
  Researchers
 
  Alumni

Jean SEVIGNY , PhD
Professor, Department of microbiology, infectious diseases and immunology, Faculty of Medicine, Université Laval.


Centre de Recherche en Rhumatologie et Immunologie
2705, boulevard Laurier, local T1-49
Québec, QC
G1V 4G2 Canada
Tél.: 418-656-4141 poste 46319 (bureau)
Tél.: 418-656-4141 poste 46171 (laboratoire)
Fax: 418-654-2765
E-mail: Jean.Sevigny@crchul.ulaval.ca

Research tool development

Distribution of anti-ectonucleotidase antibodies.
http://ectonucleotidases-ab.com/http://ectonucleotidases-ab.com/

Research Themes

Biochemistry and Physiopathology of Extracellular Nucleotides and Ectonucleotidases

Research Projects

Our laboratory studies the functions of extracellular nucleotides, the receptors by which they trigger their actions and the enzymes at the cell surface that hydrolyze them. In mammals, extracellular nucleotides act on all systems by causing a variety of physiological responses. The cells release these molecules under various conditions such as cell lysis, shear stress and cell activation. For example, platelets store nucleotides in secretory granules and release them by exocytosis during aggregation. Once released, nucleotides exert their actions primarily via P2 receptors. The extracellular concentration of nucleotides is modulated by enzymes located at the cell surface called ectonucleotidases. They convert triphospho- (e.g. ATP) and diphosphonucleosides (e.g. ADP) into nucleoside monophosphates (e.g. AMP). The Nucleoside Triphosphate Diphosphohydrolases (NTPDases) represent an important family of ectonucleotidases. The AMP produced is then converted into adenosine by the ecto-5'-nucleotidase. In turn, adenosine activates P1 receptors initiating cellular responses often opposite to those elicited by ATP. This complex system allows a tight regulation of the physiological effects associated with these molecules. The research of our laboratory focuses on the following projects:

>> CHARACTERIZATION OF MAMMALIAN NTPDASES

 

We have recently identified and purified a new NTPDase member that is strongly expressed in the biliary canaliculi of hepatocytes. One of our projects is to clone the gene that codes for this enzyme and to generate the tools to study its properties and functions. We are also involved in the identification and characterization of other NTPDases.

>> ROLES OF EXTRACELLULAR NUCLEOTIDES AND NTPDASES IN INFLAMMATION, AND IN CARDIOVASCULAR AND HEPATIC FUNCTIONS

By modulating the levels of nucleotides at the cell surface, NTPDases control various biological functions. Our objective is to test some of these functions using cellular and animal models. In inflammation, we are particularly interested in neutrophil and macrophage pathophysiology. In the cardiovascular system, we primarily study thrombosis and haemostasis as well as vascular tonicity. Finally, we also focus on nucleotide salvage and fibrosis in the liver.

These research projects are supported by
the Canadian Institutes of Health Research (CIHR),
the Fonds de la Recherche en Santé du Quebec (FRSQ)
and The Arthritis Society.

Publications

Click here.

Academic Background

BSc in Biology (concentration: Biotechnology), University of Sherbrooke, Sherbrooke, Canada, 1988.

MSc in Microbiology, Laboratory of Dr. Marcel F. Bastin, University of Sherbrooke, Sherbrooke, Canada, 1992.

PhD in Biology, Laboratory of Dr. Adrien R. Beaudoin, University of Sherbrooke, Sherbrooke, Canada, 1997.

Postdoctoral Fellowship in Vascular Biology, Laboratory of Dr. Simon C. Robson, Harvard University, Boston, USA, 1997-1999.

Instructor in Medicine (Junior Faculty), Department of Gastro-enterology, Laboratory of Dr. Simon C. Robson, Harvard University, Boston, USA, 1999-2001.

Reviews and Book Chapters

Sévigny, J. (2007) NTPDase8. AfCS-Nature Molecule Pages. doi:10.1038/mp.a003955.01. Revue électronique publiée par Nature Group: Link

Sévigny, J. (2006) NTPDase7. AfCS-Nature Molecule Pages. doi:10.1038/mp.a003166.01. Revue électronique publiée par Nature Group: Link

Robson, S.C., J. Sévigny, M. Imai, O. Guckelberger & K. Enjyoji. (2000) Thromboregulatory potential of endothelial CD39/nucleoside triphosphate diphosphohydrolase: modulation of purinergic signalling in platelets. Emerging Therapeutic Targets 4: 155-171.

Beaudoin, A.R., J. Sévigny, F.-P. Gendron, M. St-Georges & M.C. Leclerc. (1998) Prevention and reversal of thrombotic and inflammatory processes. Emerging Therapeutic Targets 2: 1-5.

Beaudoin, A.R., Sévigny, J., and Picher, M. 1996. ATP-diphosphohydrolases, apyrases, and nucleotide phosphohydrolases: biochemical properties and functions. In ATPases. (Lee A.G., ed.), Biomembranes Vol. 5, pp. 369-401. Greenwich, CT, JAI Press Inc.

Sévigny, J. & A.R. Beaudoin. (1994) Le monde des nucléotides extracellulaires (Article de synthèse). Med. Sci. 10: 836-844.

Research participants in research projects