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Health Sciences; Medical Sciences; Natural Sciences and Engineering

Christine Vande Velde

Mécanismes cellulaires à l’origine de la sclérose latérale amyotrophique (SLA)

Professeure titulaire

Faculté de médecine - Département de neurosciences

c.vande.velde@umontreal.ca

Professeure accréditée

Faculté de médecine - Département de biochimie et médecine moléculaire

c.vande.velde@umontreal.ca

Secondary numbers: 514 890-8000 #28832 (Travail 1) 514 890-8000 #30229 (Travail 2)

Profile

Research expertise

Amyotrophic lateral sclerosis (ALS) is characterized by the selective loss of motor neurons. Motor neurons are unique in both their metabolic demand and architecture, and both are intricately linked. Efficient transport of cellular cargoes along the axonal process (which can be as much as one meter in length) depends on energy supplied by mitochondria. Furthermore, mitochondria are themselves cargos of axonal transport that must be delivered to the synapse so as to provide the necessary fuel for neurotransmission. Disease pathology includes disturbances in both of these elements, namely disrupted mitochondrial ultrastructure and axonal aggregates in both familial and sporadic ALS cases.

Mouse models confirm a defect in the axonal transport of at least one defined cargo, although it remains unknown if broader errors in intracellular trafficking exist. In addition, while various defects in mitochondrial metabolism have been reported, it remains unclear if these defects are unique to motor neurons and how they might participate in disease initiation. To examine how mitochondrial trafficking and axonal transport contribute to disease in vivo, we have generated a new transgenic mouse model in which mitochondria of motor neurons are fluorescently-labeled. These mice, in combination with rodents which develop an ALS-like phenotype, will be examined. Specifically, mitochondrial trafficking, dynamics, and axonal transport will be followed in relation to disease stage using confocal imaging of live motor axons. In addition, since mitochondria from motor neurons are labeled in these animals, motor neuron mitochondria will be isolated and assessed for multiple metabolic parameters. Complementary experiments in motor neuron cultures are also used.

Awards and recognitions

  • FRQS Junior 1
  • CIHR New Investigator
  • FRQS Senior

education

  • 1997 — BSc — Génétique — University of Manitoba
  • 2001 — PhD — Biochimie — University of Manitoba

For more information…

Affiliations and responsabilities

Research affiliations

Research units

Membre

Affiliated institutions

  • Centre hospitalier de l’Université de Montréal (CHUM)

Teaching and supervision

Teaching

Courses taught (current session only)

Programs

Student supervision

Theses and dissertation supervision (Papyrus Institutional Repository)

2024

Fonction cellulaire de la HNRNP A1B, une isoforme plus longue de HNRNPA1, qui est régulée à la hausse dans la SLA/DFT

Graduate : Llasera Ballester García, Mariana
Cycle : Master's
Grade : M. Sc.
2024

Small molecule-mediated upregulation of G3BP1 as a therapy for ALS

Graduate : Shokri, Asana
Cycle : Master's
Grade : M. Sc.
2022

Évaluation du rôle biologique et pathologique de l’isoforme alternatif de HNRNPA1; hnRNP A1B

Graduate : Gagné, Myriam
Cycle : Doctoral
Grade : Ph. D.
2018

La conséquence de l’expression de hnRNP A1B sur la réponse cellulaire au stress

Graduate : Rolland, Sophie
Cycle : Master's
Grade : M. Sc.
2015

TDP-43 régule la dynamique et la fonction des Granules de Stress via G3BP1

Graduate : Aulas, Anaïs
Cycle : Doctoral
Grade : Ph. D.
2015

Uncovering the role of misfolded SOD1 in the pathogenesis of Amyotrophic Lateral Sclerosis

Graduate : Pickles, Sarah
Cycle : Doctoral
Grade : Ph. D.

Projects

Research projects

2022 - 2028

Unravelling the physiological function of a highly conserved HNRNPA1 splice variant

Lead researcher : Christine Vande Velde
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVX20965-(RGP) Programme de subvention à la découverte individuelle ou de groupe
2020 - 2026

UNDERSTANDING G3BP1 AND STRESS GRANULE DYNAMICS IN ALS PATHOGENESIS

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

Targeting G3BP1 and the stress granule response as a therapy for ALS & FTD

Lead researcher : Christine Vande Velde
Funding sources: Target ALS Foundation
Grant programs:
2015 - 2022

CROSS REGULATION OF RNA BINDING PROTEINS AND ORDERED PROTEIN AGGREGATION

Lead researcher : Christine Vande Velde
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVX20965-(RGP) Programme de subvention à la découverte individuelle ou de groupe
2018 - 2021

DÉCRYPTER LES MÉCANISMES PATHOLOGIQUES DE LA NEURODÉGÉNÉRESCENCE DANS LA SCLÉROSE LATÉRALE AMYOTROPHIQUE

Lead researcher : Christine Vande Velde
Funding sources: FRQS/Fonds de recherche du Québec - Santé (FRSQ)
Grant programs: PVXXXXXX-Bourse de chercheur-boursier : Senior
2018 - 2020

Determining the conséquences of TDP-43 mediated splice event ind hnRNP a1

Lead researcher : Christine Vande Velde
Funding sources: ALS/Amyotrophic Lateral Sclerosis Association
Grant programs:
2018 - 2020

Disease relevance of hnRNP A1B, a TDP-43 dependent splice variant of HNRNPA1

Lead researcher : Christine Vande Velde
Funding sources: SLA Canada/Société canadienne de la sclérose latérale amyotrophique
Grant programs:
2015 - 2020

Regulation of the stress granule proteome and transcriptome by TDP-43 in ALS: biomarkers and therapeutic targets

Lead researcher : Christine Vande Velde
Funding sources: SLA Canada/Société canadienne de la sclérose latérale amyotrophique
Grant programs:
2002 - 2020

SUBVENTION D'INFRASTRUCTURE DU FRSQ POUR LE GRSNC(GROUPE DE RECHERCHE SUR LE SYSTÈME NERVEUX CENTRAL)

Lead researcher : Trevor Drew , Richard Robitaille , Louis-Éric Trudeau
Co-researchers : Serge Rossignol , Yoshua Bengio , Guy Doucet , Gilles Lavigne , Allan Smith , Pierre J. Blanchet , C. Elaine Chapman , Laurent Descarries , Gary Duncan , Arlette Kolta , Jean-Claude Lacaille , Richard Warren , Lionel Carmant , Luc DesGroseillers , Adriana Di Polo , John Francis Kalaska , Yves Lamarre , Nicole Leclerc , Pierre Rainville , Jean-Pierre Gossard , Pierre Drapeau , Hélène Girouard , Jannic Boehm , Paul Cisek , Numa Dancause , Karl J.L. Fernandes , Florin Amzica , Andrea Michelle Green , Daniel Lévesque , Anne-Noël Samaha , Christine Vande Velde , Réjean Dubuc , Vincent Castellucci , Louis St-Amant , Wayne Steven Sossin
Funding sources: FRQS/Fonds de recherche du Québec - Santé (FRSQ)
Grant programs: PVXXXXXX-Subvention de groupe de recherche
2017 - 2019

High performance nucleofection unit for difficult to manipulate cell types

Lead researcher : Christine Vande Velde
Co-researchers : Nicole Leclerc , Karl J.L. Fernandes , Nathalie Arbour
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-(OIR) Outils et d'instruments de recherche (de 7 001 $ à 150 000 $)
2016 - 2019

Misfolded SOD1 species and mitochondrial quality control in ALS

Lead researcher : Christine Vande Velde
Funding sources: Muscular Dystrophy Association
Grant programs:
2013 - 2018

EMERGING TEAM TO IDENTIFY AND CHARACTERIZE NOVEL AND EXISTING HEREDITARY SPASTIC PARAPELGIA (HSP) DISEASE GENES.

Lead researcher : Guy Rouleau
Co-researchers : Pierre Drapeau , Alex Parker , Christine Vande Velde
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs:
2013 - 2018

CELL BIOLOGICA MECHANISMS OF TDP-43 IN AMYOTROPHIC LATERAL SCLEROSIS

Lead researcher : Christine Vande Velde
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-Subvention de fonctionnement: recherche neuromusculaire
2013 - 2018

IMPACT OF TDP-43 ON STRESS GRANULE SIGNALING IN ALS ATION AND PROMOTE ISLET REGENERATION

Lead researcher : Christine Vande Velde
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXX5664-Bourse salariale pour nouveau chercheur
2015 - 2017

Misfolded SOD1 species in ALS pathogenesis

Lead researcher : Christine Vande Velde
Funding sources: SLA Canada/Société canadienne de la sclérose latérale amyotrophique
Grant programs:
2012 - 2017

CELL BIOLOGICAL MECHANISMS OF TDP-43 IN AMYOTROPIC LATERAL SCLEROSIS

Lead researcher : Christine Vande Velde
Funding sources: IRSC/Instituts de recherche en santé du Canada , SLA Canada/Société canadienne de la sclérose latérale amyotrophique
Grant programs: ,
2012 - 2017

EMERGING TEAM TO IDENTIFY AND CHARACTERIZE NOVEL AND EXISTING HEREDITARY SPASTIC PARAPLEGIA (HSP) DISEASE GENES

Lead researcher : Guy Rouleau
Co-researchers : Pierre Drapeau , Alex Parker , Christine Vande Velde , Peter Ray , Grace Yoon , Oksana Suchowersky , Jillian Parboosingh , François Bolduc , Nicolas Dupré , Kym Boycott
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-Subvention d'équipe émergente: maladies rares
2010 - 2016

ROLE OF TDP-43 IN CELLULAR STRESS RESPONSE

Lead researcher : Christine Vande Velde
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVX20965-(RGP) Programme de subvention à la découverte individuelle ou de groupe
2012 - 2015

IMPACT OF TDP-43 ON STRESS GRANULE SIGNALING IN ALS

Lead researcher : Christine Vande Velde
Funding sources: Muscular Dystrophy Association
Grant programs:
2009 - 2014

ROLE OF TDP-43 IN CELLULAR STRESS RESPONSE

Lead researcher : Christine Vande Velde
2012 - 2013

FUNCTIONAL IMPLICATIONS OF MISFOLDED SOD1 ON MITOCHONDRIA IN ALS

Lead researcher : Christine Vande Velde
Funding sources: Bruno and Ilse Frick Foundation for Research on ALS
Grant programs:
2008 - 2013

CELLULAR AND BIOCHEMICAL IMPACT OF TDP-43 MUTANTS IN ALS

Lead researcher : Guy Rouleau
Co-researchers : Alex Parker , Christine Vande Velde , Jean-Pierre Julien
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXX5647-(MOP) Subvention de fonctionnement incluant les subventions de fonctionnement programmatiques (général)
2008 - 2011

IDENTIFICATION DES MECANISMES DE DEGENERESCENCE DU MOTONEURONE DANS LA SCLEROSE LATERALE AMYOTROPHIQUE (SLA)

Lead researcher : Christine Vande Velde

Outreach

Publications and presentations

Publications

Publications choisies

  • K.K. McDonald, A. Aulas, L. Destroismaisons, S. Pickles, E. Beleac, W. Camu, G.A. Rouleau, and C. Vande Velde. (2011). TAR DNA-Binding Protein 43 (TDP-43) regulates stress granule dynamics via differential regulation of G3BP and TIA-1. Human Molecular Genetics 20:1400-10;
  • C. Vande Velde#, K.K. McDonald, Y. Boukhedimi, M. McAlonis-Downes, C.S. Lobsiger, S. Bel Hadj, A.N. Zandona, J.P. Julien, S.B. Shah and D.W. Cleveland#. (2011). Misfolded SOD1 associated with motor neuron mitochondria alters mitochondrial shape and distribution prior to clinical onset. PLoS One 6:e22031;
  • S. Pickles and C. Vande Velde. (2012) Misfolded SOD1 and ALS: Zeroing in on mitochondria. Amyotrophic Lateral Sclerosis 13:333-40;
  • A. Aulas, S. Stabile and C. Vande Velde. (2012). Endogenous TDP-43, but not FUS, contributes to stress granule assembly via G3BP. Molecular Neurodegeneration 7:54;
  • S Pickles, L. Destroismaisons, S.L. Peyrard, S. Cadot, R.H. Brown Jr, G.A. Rouleau, J.P. Julien, N. Arbour and C. Vande Velde. (2013). Mitochondrial damage revealed by immunoselection for ALS-linked misfolded SOD1. Human Molecular Genetics 22:3947-39;
  • S. Pickles, M. Cadieux-Dion, J.I. Alvarez, M.A. Lécuyer, S. Peyrard, L. Destroismaisons, L. St.-Onge, S. Terouz, P. Cossette, A. Prat and C. Vande Velde. (2013). Endo-MitoEGFP mice: A novel transgenic mouse with fluorescently marked mitochondria in microvascular endothelial cells. PLOS One 8:e74603.

Disciplines

  • Neurosciences
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Areas of expertise

  • Neurodegenerative Diseases (Aging)
  • Proteomics
  • Nucleic Acids
  • Transgenic Model
  • Molecular Genetics