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Health Sciences; Medical Sciences

Luc DesGroseillers

Dynamique cellulaire des macromolécules

Professeur titulaire

Faculté de médecine - Département de biochimie et médecine moléculaire

Roger-Gaudry, room E-517

514 343-5802

luc.desgroseillers@umontreal.ca

Profile

Research expertise

Our research aims to characterize ribonucleoprotein complexes involved in mRNA transport and define their role in the post-transcriptional regulation of gene expression. More specifically, we characterize distinct mechanisms of mRNA transport and define the physiological roles of these transports for different cellular processes such as synaptic plasticity and cell cycle progression.

The regulation of gene expression at the post-transcriptional level is a mechanism widely used by mammalian cells to control protein synthesis with acute precision. Sequences or structural elements usually in the 3’UTR of mRNA are recognized by different RNA-binding proteins such as Stau1 and/or non-coding RNAs that assemble together in messenger ribonucleoproteins (mRNPs) and mediate an effect on mRNA metabolism. These observations lead to the “post-transcriptional RNA regulon” hypothesis that RNA-binding proteins group and tag functionally related mRNAs to orchestrate their splicing, export, stability, localization and translation so that mRNA expression is efficiently coordinated with cell needs. Deregulation of an RNA regulon is associated with complex human diseases such as Fragile X Mental Retardation, neurodegenerative diseases, myotonic dystrophy, cancer and immunoregulatory disorders. The mechanisms that allow inhibition-activation of RNA regulon are still largely unknown.The critical determining factor for post-transcriptional regulation of gene expression is whether and how an mRNA is recognized by specific RNA-binding proteins (RBPs). RBPs play distinct roles in this process:
  1. they organize the macromolecular transport complex;
  2. they act as translational repressors that prevent translation of mRNA cargos until transport is achieved;
  3. they regulate the activation of translation of the protein following transport and degradation of mRNAs.
Mammalian Staufen is involved in several steps of post-transcriptional gene expression, regulating mRNA transport, mRNA decay and translation. In theory, the dual function of Staufen in mRNA decay and translation stimulation may allow the coordinate up-regulation of proteins required for a specific cell function and down-regulation of proteins with opposite functions. Not surprisingly then for a key protein, an increasingly abundant literature links Stau1 expression to different physiological processes such as synaptic maintenance and plasticity, cell differentiation, meiotic maturation, HIV-1 virus replication and cell growth. Understanding the roles of Staufen in the regulation of post-transcriptional gene expression will allow us to screen for a link between Staufen and human health problems such as cancers, viral infection and neurodegenerative diseases.Major ongoing projects :
  1. Molecular characterization of ribonucleoprotein complexes involved in mRNA transport, localization and local translation;
  2. Functional characterization of proteins involved in mRNA transport, localization and local translation;
  3. Physiological importance of mRNA transport and local translation on synaptic plasticity and cell cycle progression.
Our ongoing projects aim to :
  1. Define, at the molecular level, different types of mRNA transport in dendrites and axons of neurons;
  2. Link different types of mRNA transport to distinct phenomena involved in synaptic plasticity;
  3. Define the physiological role of Staufen in synaptic plasticity;
  4. Define the role of Staufen in the regulation of post-transcriptionnal gene expression;
  5. Define the role of Staufen in neurons and in dividing cells.

Biography

Dr DesGroseillers est professeur titulaire au Département de biochimie et médecine moléculaire de l’Université de Montréal. Il a fait ses études de doctorat à I’IRCM en virologie moléculaire à l’Université de Montréal et a poursuivi ses études postdoctorales à l’Université Stanford en neurobiologie moléculaire. Il est responsable, depuis plusieurs années, des programmes d’études supérieures au Département de biochimie et médecine moléculaire. Les activités de recherche de son laboratoire portent sur les mécanismes moléculaires de la prolifération cellulaire.

Affiliations and responsabilities

Research affiliations

Teaching and supervision

Student supervision

Theses and dissertation supervision (Papyrus Institutional Repository)

2019

Staufen1 est un régulateur post-transcriptionnel du cycle cellulaire

Graduate : Ghram, Mehdi
Cycle : Doctoral
Grade : Ph. D.
2012

Caractérisation des complexes ribonucléoprotéiques de Staufen1 et Staufen2

Graduate : Maher Laporte, Marjolaine
Cycle : Doctoral
Grade : Ph. D.
2011

Stabilité de l’acide ribonucléique pour la datation des fluides corporels en biologie judiciaire

Graduate : Simard, Anne-Marie
Cycle : Master's
Grade : M. Sc.
2009

Étude de l’activité de Staufen1 dans la régulation traductionnelle de certains ARNm

Graduate : Dugré-Brisson, Samuel
Cycle : Doctoral
Grade : Ph. D.
2007

Expression des récepteurs EphA dans le raphé dorsal néonatal et adulte

Graduate : Baharnoori, Moogeh
Cycle : Master's
Grade : M. Sc.
2005

Surexpression neuronale de l'EPN et génération/caractérisation de souris invalidées NL1/EPN

Graduate : Sabourin, Valérie
Cycle : Master's
Grade : M. Sc.
2005

Caractérisation de sacsine, la protéine responsable de l'ataxie de Charlevoix-Saguenay

Graduate : Leblanc, Chantal
Cycle : Master's
Grade : M. Sc.
2005

Caractérisation moléculaire des complexes ribonucléoprotéiques des neurones de mammifères

Graduate : Elvira, George
Cycle : Doctoral
Grade : Ph. D.
2003

Caractérisation du transport nucléocytoplasmique de la protéine Staufen chez les mammifères

Graduate : Martel, Catherine
Cycle : Master's
Grade : M. Sc.

Projects

Research projects

2019 - 2025

Staufen2 and DNA damage

Lead researcher : Luc DesGroseillers
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 - 2023

Senescent macrophages promote pancreatic tumorigenesis: a link between cancer and aging

Lead researcher : Gerardo Ferbeyre
Co-researchers : Luc DesGroseillers
Funding sources: SRC/Société de recherche sur le cancer
Grant programs: PVX12154-Subvention de recherche
2019 - 2022

FEI Sans Restriction pour le département de biochimie et médecine

Lead researcher : Luc DesGroseillers
Funding sources: Université de Montréal
Grant programs: PVXXXXXX-FEI sans restriction
2014 - 2021

EXPRESSION OF STAUFEN2 IN RESPONSE TO DNA DAMAGES

Lead researcher : Luc DesGroseillers
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
2002 - 2020

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

Funding sources: FRQS/Fonds de recherche du Québec - Santé (FRSQ)
Grant programs: PVXXXXXX-Subvention de groupe de recherche
2016 - 2019

Role of Staufen1 in the regulation of cell proliferation

Lead researcher : Luc DesGroseillers
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-(PJT) Subvention Projet
2011 - 2017

REGULATION OF STAUFEN1-MEDIATED MRNA DECAY BY PHOSPHORYLATION AND CONSEQUENCE FOR G1-S PROGRESSION

Lead researcher : Luc DesGroseillers
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXX5647-Subvention de fonctionnement incluant les subventions de fonctionnement programmatiques
2010 - 2015

REGULATION OF STAUFEN1-MEDIATED MRNA DECAY BY PHOSPHORYLATION AND CONSEQUENCE FOR G1-S PROGRESSION

Lead researcher : Luc DesGroseillers
1996 - 2015

STAUFEN1-MEDIATED POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION

Lead researcher : Luc DesGroseillers
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
2009 - 2014

ROLES OF THE RNA-BINDING PROTEIN STAUFEN IN THE CONTROL OF CELL CYCLE PROGRESSION

Lead researcher : Luc DesGroseillers
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXX5647-Subvention de fonctionnement incluant les subventions de fonctionnement programmatiques
2009 - 2013

ROLES OF THE RNA-BINDING PROTEIN STAUFEN IN THE CONTROL OF CELL CYCLE PROGRESSION

Lead researcher : Luc DesGroseillers
2009 - 2013

STAUFEN1-MEDIATED POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION

Lead researcher : Luc DesGroseillers

Outreach

Publications and presentations

Publications

Zhang, X., Trepanier, V., Beaujois, R., Viranaicken, W., Drobetsky, E., and DesGroseillers, L. (2016) Down-regulation of Staufen2 expression in response to DNA damages facilitates apoptosis. Nucl. Acid Res. doi: 10.1093/nar/gkw057

Boulay, K., Ghram, M., Viranaicken, W., Trépanier, V., Mollet, S., Fréchina, C., and DesGroseillers, L. (2014) Cell cycle-dependent regulation of the RNA-binding protein Staufen1. Nucl. Acid Res 42, 7867-7883.

Ravel-Chapuis, A., Bélanger, B., Yadava, R.S., Mahadevan, M.S., DesGroseillers, L., Côté, J., and Jasmin, B.J. (2012) The RNA-binding protein Staufen1 is increased in DM1 skeletal muscle and promotes alternative pre-mRNA splicing. J. Cell Biol. 196, 699-712

Lebeau, G., Miller, L.C., Tartas, M., McAdam, R., Laplante, I., Badeaux, F., DesGroseillers, L., Sossin, W.S., and Lacaille, J.-C. (2011) Staufen 2 regulates mGluR long-term depression and Map1b mRNA distribution in hippocampal pyramidal cells. Learning and Memory 18, 314-326.

Bidinosti, M., Ran, I., Sanchez-Carbente, M.R., Martineau, Y., Gingras, A.-C., Gkogkas, C., Raught, B., Bramham, C., Sossin, W.A., Costa-Mattioli, M., DesGroseillers, L., Lacaille, J.C., and Sonenberg, N. (2010) Postnatal deamidation of 4E-BP2 in brain enhances its association with Raptor and alters kinetics of excitatory synaptic transmission. Mol Cell. 37, 797-808.

Lebeau, G., Maher-Laporte, M., Topolnik, L., Laurent, C.E., Sossin, W.S., DesGroseillers L., and Lacaille, J.-C. (2008). Staufen1 regulation of protein synthesis-dependent long-term potentiation and synaptic function in hippocampal pyramidal cells. Mol. Cell. Biol. 28, 2896-2907.

Kim, Y.K., Furic, L., Parisien, M., Major, F., DesGroseillers, L., and Maquat, L.E. (2007). Staufen1 Regulates Diverse Classes of Mammalian Transcripts. EMBO J 26, 2670-2681.

Elvira, G., Wasiak, S., Blandford, V., Tong, X.K., Serrano, A., Fan, X., Sanchez-Carbente, M.R., Servant, F., Bell, A.W., Boismenu, D., Lacaille, J.-C., McPherson, P.S., DesGroseillers, L. and Sossin, W.S. (2006). Characterization of an RNA granule from developing brain. Mol. Cell. Proteomics 5, 635-651.

Kim, Y.K., Furic, L., DesGroseillers, L., and Maquat, L.E. (2005). Mammalian Staufen1 Recruits Upf1 to Specific mRNA 3’UTRs so as to Elicit mRNA Decay. Cell 120, 195-208.

Disciplines

  • Molecular Biology

Areas of expertise

  • Cellular Division
  • Gene Regulation and Expression
  • Apoptosis and Cancer
  • Macromolecules