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  Sylvain Bourgoin     
 
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  Fawzi Aoudjit          
  Pierre Borgeat        
  Maria Fernandes     
  Louis Flamand         
  François Marceau          
  Paul Naccache     
  Patrice Poubelle      
  Marc Pouliot            
  Patrick Provost        
  Raynald Roy            
  Jean Sévigny           
 
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Jean SEVIGNY, PhD
Associate Professor, Department of Anatomy and Physiology, Faculty of Medicine, Université Laval.


Centre de Recherche en
Rhumatologie et Immunologie
2705, Boulevard Laurier, local T1-49
Quebec, QC
G1V 4G2 Canada
Tel: 418-656-4141 ext. 46319 (office)
Tel: 418-656-4141 ext. 46171 (laboratory)
Fax: 418-654-2765
E-mail:
Jean.Sevigny@crchul.ulaval.ca

Research Themes | Research Projects | Selected References | List of Publications | Research Personnel | Additional Information

Research Themes

Biochemistry and Physiopathology of Extracellular Nucleotides and Ectonucleotidases

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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.

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>> 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.

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Selected references  
 

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 canalicular ecto-ATPase as NTPDase8. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G785-95. PubMed

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: 1269-75. PubMed

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. Biochemistry. 43: 5511-9. PubMed

Sévigny, J., Sundberg, C., Braun, N., Guckelberger, O., Csizmadia, E., Qawi, I., Imai, M., Zimmermann, H., and Robson, S.C. 2002. Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation. Blood 99:2801-2809. PubMed

Mizumoto, N., Kumamoto, T., Robson, S.C., Sévigny, J., Matsue, H., Enjyoji, K., and Takashima, A. 2002. CD39 is the dominant Langerhans cell-associated ecto-NTPDase: Modulatory roles in inflammation and immune responsiveness. Nat. Med. 8:358-365. PubMed

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List of Publications - PubMed Link

Research Personnel      
  Adjunct Professor     dot
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  Filip Kukulski, PhD  

 

 
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  Research Assistants   Graduate Students
  Julie Pelletier, DEC
Alain Tremblay, BSc
 

Fethia Ben Yebdri, MSc
Elizandra Braganhol, MSc
Michel Fausther, MSc
Cristina Fürstenau Basso, MSc
Sébastien Lévesque, MSc
Élise Lavoie, MSc

 
  Postdoctoral Fellows

Fariborz Bahrami, PhD
Gilles Kauffenstein, PhD
Joanna Lecka, PhD

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Additional Information Details