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Alexei Pchejetski

Mécanismes fondamentaux de la fonction du lysosome

Professeur titulaire

Faculté de médecine - Département de pédiatrie

alexei.pchejetski@umontreal.ca

Secondary numbers: 514 345-4931 (Travail 1) 514 345-4801 (Télécopieur)
Secondary email: alex@justine.umontreal.ca (Travail)

Profile

Research expertise

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 called 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 the deficiencies of lysosomal sialidases (sialidosis, galactosialidosis) and N-acetyltransferases (mucopolysaccharidosis IIIC).Sialic acids and sialidases in cell signallingSialic 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 elastogenesisShort vasoactive peptides are recognized as potent regulators of blood circulation. Through their interaction with different cell surface receptors peptides can modulate blood pressure by such diverse mechanisms as contracting vascular smooth muscles, increasing or decreasing plasma volume, or by induction or suppression of vascular wall remodelling. Therefore proteases involved in the catabolic proteolysis of circulating vasoactive peptides, which regulates their functional longevity and availability play important role in 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 phosphoproteomicsPhosphorylation 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 development of 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.

Affiliations and responsabilities

Research affiliations

Teaching and supervision

Student supervision

Theses and dissertation supervision (Papyrus Institutional Repository)

Projects

Research projects

2022 - 2028

Neuroprotective peptides for treatment of neurological lysosomal diseases

Lead researcher : Alexei Pchejetski
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-(PJT) Subvention Projet
2018 - 2024

Novel Treatments for Lysosomal Neurological Disorders: Targeting Microglia Cells and Misfolded Proteins for Therapy of Mucopolysaccharidosis IIIC

Lead researcher : Alexei Pchejetski
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-(PJT) Subvention Projet
2022 - 2023

Programme de recherche pour le développement de thérapies innovantes basées sur le génie génétique des cellules et des tissus pour le traitement des maladies monogéniques et des cancers pédiatriques

Funding sources: FCI/Fondation canadienne pour l'innovation
Grant programs: PVXXXXXX-Fonds d'innovation
2021 - 2023

Neuroprotective peptides for treatment of neurological lysosomal diseases

Lead researcher : Alexei Pchejetski
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXX5647-(MOP) Subvention de fonctionnement incluant les subventions de fonctionnement programmatiques (général)
2016 - 2023

Neuraminidase 1 as a trigger of immune thrombocytopenia: using animal models to understand pathophysiology of the disease and develop novel therapies.

Lead researcher : Alexei Pchejetski
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-(PJT) Subvention Projet
2020 - 2022

(GlycoNet)/Regulation of inflammatory response to bacterial infections by human neuraminidase enzymes

Co-researchers : Alexei Pchejetski
Funding sources: Secrétariat Inter-Conseil et Réseaux des centres d'excellence (RCE)
Grant programs: PV143493-(RCE) Réseaux de centres d'excellence
2020 - 2022

GlycoNet/Innovative therapies for neurological lysosomal storage disorders.

Co-researchers : Alexei Pchejetski
Funding sources: Secrétariat Inter-Conseil et Réseaux des centres d'excellence (RCE)
Grant programs: PV143493-(RCE) Réseaux de centres d'excellence
2015 - 2020

Réseau GlycoNet/Neuraminidases as a trigger of atherosclerosis.

Co-researchers : Alexei Pchejetski
Funding sources: Secrétariat Inter-Conseil et Réseaux des centres d'excellence (RCE)
Grant programs: PV143493-(RCE) Réseaux de centres d'excellence
2018 - 2019

Targeting Missfolded Proteins for Therapy of MPSIIIC

Lead researcher : Alexei Pchejetski
Funding sources: Sanfilippo Children's Foundation
Grant programs:
2017 - 2018

Rare Diseases: Models & Mechanisms Network. Canadian "rare diseases: models & mechanisms" network (RDMM) / Réseau canadien "maladies rares : modèles et mécanismes"

Lead researcher : Philip A Hieter
Co-researchers : Alexei Pchejetski
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-Subvention de réseau
2017 - 2018

Novel Treatments for Lysosomal Neurological Disorders: Targeting Microglia Cells and Missfolded Proteins for Therapy of Mucopolysaccharidosis IIIC

Lead researcher : Alexei Pchejetski
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-(PJT) Subvention Projet
2016 - 2018

Enzyme replacement therapy for Sanfilippo disease type C. Chaperone therapy for mucopolysaccharidosis IIIC (MPS IIIC). Synaptic Dysfunction in Lysosomal Storage Disorders: Pathogenic Mechanism and Potential Therapeutic Applications.

Lead researcher : Alexei Pchejetski
Funding sources: JLK Sanfilippo Research Foundation
Grant programs:
2016 - 2017

Neuraminidases as a trigger of atherosclerosis.

Lead researcher : Alexei Pchejetski
Funding sources: Mizutani Foundation for Glycoscience
Grant programs:
2016 - 2017

Rare Diseases: Models & Mechanisms Network. Canadian "rare diseases: models & mechanisms" network (RDMM) / Réseau canadien "maladies rares : modèles et mécanismes"

Lead researcher : Philip A Hieter
Co-researchers : Alexei Pchejetski
Funding sources: Genome British Columbia
Grant programs:
2016 - 2017

Neuraminidase 1 as a trigger of immune thrombocytopenia

Lead researcher : Alexei Pchejetski
Funding sources: Fondation Charles Bruneau
Grant programs:
2010 - 2016

MUCOPOLYSACCHARIDOSIS IIIC AS A PROTEIN FOLDING DISEASE : USING ANIMAL MODELS TO STUDY PATHOPHYSIOLOGY AND EXPLORE POTENTIAL THERAPEUTIC SOLUTIONS

Lead researcher : Alexei Pchejetski
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXX5647-(MOP) Subvention de fonctionnement incluant les subventions de fonctionnement programmatiques (général)
2010 - 2015

MUCOPOLYSACCHARIDOSIS IIIC AS A PROTEIN FOLDING DISEASE: USING ANIMAL MODELS TO STUDY PATHOPHYSIOLOGY AND EXPLORE POTENTIAL THERAPEUTIC SOLUTIONS

Lead researcher : Alexei Pchejetski
2010 - 2015

LIPOLYSIS : BIOCHEMICAL GENETICS, PHYSIOLOGY AND MOLECULAR CIRCUITRY

Lead researcher : Grant Mitchell
Co-researchers : Pierre Thibault , Alexei Pchejetski , Marie-Hélène Roy-Gagnon
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXX5647-(MOP) Subvention de fonctionnement incluant les subventions de fonctionnement programmatiques (général)
2009 - 2015

SERINE CARBOXYPEPTIDASES THAT INACTIVATE SHORT VASOACTIVE PEPTIDES : ROLES IN VASOCONSTRICTION AND PROLIFERATION OF VASCULAR SMCS

Lead researcher : Alexei Pchejetski
Co-researchers : Aleksander Hinek
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXX5647-(MOP) Subvention de fonctionnement incluant les subventions de fonctionnement programmatiques (général)
2012 - 2014

IDENTIFICATION DES OLIGOSACCHARIDES D'HEPARANE SULFATES PATHOGENIQUES DANS LE SYNDROME SANFILIPPO C, MALADIE NEURODEGENERATIVE PEDIATRIQUE

Lead researcher : Alexei Pchejetski
Co-researchers : Grant Mitchell
Funding sources: FRQNT/Fonds de recherche du Québec - Nature et technologies (FQRNT)
Grant programs: PVXXXXXX-Développement de partenariats stratégiques en matière d'enseignement et de recherche
2009 - 2014

SERINE CARBOXYPEPTIDASES THAT INACTIVATE SHORT VASOACTIVE PEPTIDES : ROLES IN VASOCONSTRICTION AND PROLIFERATION OF VASCULAR SMCS

Lead researcher : Alexei Pchejetski
2011 - 2013

IDENTIFICATION DES OLIGOSACCHARIDES D'HÉPARANE SULFATES PATHOGÉNIQUES DANS LE SYNDRÔME SANFILIPPO C, MALADIE NEURODÉGÉNÉRATIVE PÉDIATRIQUE

Lead researcher : Alexei Pchejetski
2008 - 2011

CARBOXYPEPTIDASES THAT INACTIVE SHORT VASOACTIVE PEPTIDES: ROLES IN VASOCONSTRICTION AND PROLIFERATION OF VASCULAR SMCS

Lead researcher : Alexei Pchejetski

Outreach

Publications and presentations

Areas of expertise

  • Nucleic Acids
  • Blood Flow and Transfusions
  • Enzymes and Proteins
  • Functional and Structural Proteomics
  • Immune Reactions
  • Cell Signaling (Circulatory and Respiratory Health)