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PSHEZHETSKY , Alexey V.  PhD
 
 
     
 
Research Axis
 
   
 
 
 
Research Theme
 
   
 
 
 
Address
 
 
CHU Sainte-Justine
 
 
Centre de recherche
 
 
3175 Chemin de la Côte Sainte-Catherine
 
 
Montréal  (QC), Canada
 
 
H3T 1C5
 
     
 
Phone
 
 
514 345-4931 #2736
 
 
 
 
Fax
 
 
514 345-4766
 
     
     
     

alexei.pshezhetsky@recherche-ste-justine.qc.ca
 
 
Career Summary, Research Topics and Interests
 

Titles

  • Professor, Department of Pediatrics, University of Montreal, 2006.

  • Adjunct Professor, Department of Anatomy and Cell Biology, McGill University, 2005.

  • Adjunct Professor, Department of Biochemistry, University of Montreal, 1998.

Education

  • Postdoctorate in Medical Science, Academy of Medical Sciences, Moscow, Russia, 1990.

  • PhD in Biochemistry, Moscow State University, Russia, 1988.

  • Master's in Biochemistry, Moscow State University, Russia, 1985.


Research Interests

Lysosomal biology and lysosomal storage diseases

Lysosomes are cytoplasmic organelles harbouring over 100 hydrolytic enzymes involved in the degradation of essentially all types of biological macromolecules. Any failure in the biogenesis, lysosomal targeting, supramolecular organization or function of one or more lysosomal enzymes can result in the progressive metabolic diseases known as lysosomal storage diseases because of the massive accumulation of the undegraded substrates of the deficient enzymes in the lysosomes of the affected tissues. Our research aims at discovering the genes mutated in lysosomal diseases, identifying the molecular and biochemical defects in patients and developing therapies with a special emphasis on diseases caused by deficiencies in lysosomal sialidases (sialidosis, galactosialidosis) and N-acetyltransferases (mucopolysaccharidosis IIIC).

Sialic acids and sialidases in cell signalling

Sialic acids are abundantly expressed on the cell surface and implicated in mediating recognition between the cells, between the cells and extracellular matrix as well as between the cells and a range of pathogenic viruses, bacteria and protozoa during the inflammatory and immune reactions. Much less is known about the role of sialidases (also called neuraminidases) and sialotransferases that can regulate cellular affinity by modifying the sialylation of cell surface molecules. Using the genetically targeted mouse models, we study the role of neuraminidase 1 (Neu1) in signalling during the immune response, phagocytosis and glucose uptake, as well as the role of neuraminidase 4 (Neu4) in brain development.

Serine carboxypeptidases in regulation of vasoconstriction and elastogenesis

Short vasoactive peptides are recognized as potent regulators of blood circulation. Through their interaction with different cell surface receptors, peptides can modulate blood pressure by diverse mechanisms such as contracting vascular smooth muscles, increasing or decreasing plasma volume, or inducing or suppressing vascular wall remodelling. Therefore, proteases involved in the catabolic proteolysis of circulating vasoactive peptides, which regulates their functional longevity and availability, play an important role in the regulation of vascular resistance. Using the knock-out mouse model we study the input of the major lysosomal serine carboxypeptidase A (cathepsin A) in post-translational processing of vasoactive peptides including angiotensin and endothelin.

Functional proteomics and phosphoproteomics

Phosphorylation is the most frequent and important post-translational modification of proteins. Despite intensive research dedicated to development of methods for the analysis of a phosphoproteome, identification of low-abundant cellular phosphoproteins still remains challenging, highlighting the need for novel techniques. Our team is involved in developing new technologies for the global analysis and quantitative analysis of a phosphoproteome based on affinity resins for isolation of phosphopeptides and phosphoproteins and isotopic peptide tags. This technology should allow comparison of phosphoproteomes tracing up- and down-regulation of the individual proteins in order to identify novel drug targets and pharmacologically relevant metabolic and signaling pathways.


 
Awards and Distinctions
 
  • National Research Scholar, Fonds de la recherche en santé du Québec (FRSQ), April 2002.

  • Pediatric Excellence Award, Foundation of Stars, November 2001.

  • Senior Researcher Scholar, FRSQ, April 1999.

  • Junior 2 Research Scholar, FRSQ, June 1997.

 
Most Important Publications Selected by the Researcher
 
Seyrantepe V, Hinek A, Peng J, Fediaev M, Ernest S, Kadota Y, Canuel M, Itoh K, Morales C, Lavoie J, Tremblay J, Pshezhetsky AV,
Enzymatic activity of lysosomal carboxypeptidase (cathepsin) a is required for proper elastic fiber formation and inactivation of endothelin-1
Circulation 2008  1973-1981.
 
   
Pshezhetsky AV, Fediaev M, Ashmarina L, Mazur A, Budman L, Sinnett D, Labuda D, Beaulieu J-F, Ménard D, Nifantiev I, Levy E,
Subcellular proteomics of cell differententiation: Quantitative analysis of the plasma membrane protein of Caco-2 cells
Proteomics 2007  2201-2215.
 
   
Hrebicek M, Mrazova L, Seyrantepe V, Durand S, Roslin NM, Noskova L, Hartmannova H, Ivanek R, Cizkova A, Poupetova H, Sikora J, Urinovska J, Stranecky V, Zeman J, Lepage P, Roquis D, Verner A, Ausseil J, Beesley CE, Maire I, Poorthuis B, van de Kamp J, van Diggelen O, Wevers RA, Hudson TJ, Fujiwara TM, Majewski J, Morgan K, Smoch S, Pshezhetsky AV,
Mutations in TMEM76 Cause Mucopolysaccharidosis IIIC (Sanfilippo C Syndrome)
Am J Hum Genet 2006  807-819.
 
   
Raymond MA, Désormeaux A, Laplante P, Vigneault N, Filep JG, Landry K, Pshezhetsky AV, Hébert MJ,
Apoptosis of endothelial cells triggers a caspase-dependent anti-apoptotic paracrine loop active on VSMC
FASEB J 2004  705-707.
 
   
Taurin S, Seyrantepe V, Orlov SN, Tremblay T-L, Thibault P, Bennett MR, Hamel P, Pshezhetsky AV,
Proteome analysis and functional expression identify mortalin as an antiapoptotic gene induced by elevation of [Na+]i/[K+]i ratio in cultured vascular smooth muscle cells
Circ Res 2002  915-922.
 
   
Publications reported to FRSQ
 
 
 
 
























 
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