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El Bachir Affar

Signalisation cellulaire via l'ubiquitination

Professeur sous octroi agrégé

Faculté de médecine - Département de médecine

el.bachir.affar@umontreal.ca

Professeur accrédité

Faculté de médecine - Département de biochimie et médecine moléculaire

el.bachir.affar@umontreal.ca

Secondary numbers: 514 252-3400 #3343 (Travail 1) 514 252-3430 (Télécopieur) 514 252-3400 #4683 (Travail 2)
Secondary email: aelbachir.hmr@ssss.gouv.qc.ca (Travail)

Profile

Research expertise

Ubiquitination of proteins is a post-translational modification required for a wide spectrum of biological functions, and defects in several processes involving ubiquitination underlie human diseases. The best characterized ubiquitination reaction involves the formation of polyubiquitin chains, leading to the degradation of target proteins by the proteasome. However, ubiquitination is a complex modification that also mediates cellular functions other than protein degradation. Protein modification by ubiquitin is a reversible reaction and specific proteases can remove the ubiquitin moiety. A vast repertoire of deubiquitinases (DUBs), including approximately 80 genes, are encoded by the human genome, and are emerging as important regulators of the ubiquitination-mediated processes. As the DUBs are largely unknown, establishing the biological functions and the molecular mechanisms of these proteases is not only a crucial step toward understanding ubiquitin-mediated signaling, but is also a fundamental aspect of cancer biology. We use functional genomics and proteomics approaches to determine the functions and mechanisms of action of DUB enzymes. Our investigations are primarily on DUB genes that are important for the expression and stability of the genome.

Biography

Le Dr El Bachir Affar est titulaire d’un doctorat en physiologie-endocrinologie du Centre hospitalier de l’Université Laval (CHUL), ainsi que de deux postdoctorats : le premier du Laboratoire de recherche sur le cancer de la peau du CHUL, et le deuxième du département de pathologie de la Harvard Medical School. Il s’intéresse principalement à la signalisation cellulaire via l’ubiquitination, aux processus associés à l’ADN et à la chromatine (transcription et réparation de l’ADN), et aux bases moléculaires du cancer.

Awards and recognitions

1999 :

  • Tableau d’honneur du doyen (Ph. D.), Université Laval
  • Chercheur-boursier - Junior 1, Fonds de recherche du Québec – Santé (FRQS)
  • Bourse Taplin, Université Harvard
  • Bourse de nouveau chercheur, Instituts de recherche en santé du Canada (IRSC)

2011 :

  • Finaliste, Prix de nouveau chercheur principal Maud Menten, Institut de génétique, IRSC

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Affiliations and responsabilities

Research affiliations

University service and activities

Activities within organizations or entities of the institution

Teaching and supervision

Student supervision

Theses and dissertation supervision (Papyrus Institutional Repository)

2018

Régulation du complexe suppresseur de tumeurs BAP1/ASXL2 par ubiquitination

Graduate : Ahmed, Oumaima
Cycle : Master's
Grade : M. Sc.
2016

Étude fonctionnelle d’un nouveau complexe multi-enzymatique régulant l’épigénome

Graduate : Daou, Salima
Cycle : Doctoral
Grade : Ph. D.
2016

Biochemical and functional characterization of the tumor suppressors BRCA1 and BAP1

Graduate : Hammond-Martel, Ian
Cycle : Doctoral
Grade : Ph. D.
2014

Regulation of BAP1 tumor suppressor complex by post-translational modifications

Graduate : Mashtalir, Nazar
Cycle : Doctoral
Grade : Ph. D.
2011

Rôle de la déubiquitinase BAP1 dans la réponse cellulaire aux dommages à l'ADN

Graduate : Ghram, Mehdi
Cycle : Master's
Grade : M. Sc.

Projects

Research projects

2015 - 2022

UNRAVELING THE FUNCTION AND THE MECHANISM OF ACTION OF THE DEUBIQUITINASE MYSM1

Lead researcher : El Bachir Affar
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
2017 - 2019

A Benchtop Cell Sorter for Accelerating the Discovery of Physiopathological Processes

Lead researcher : Éric Milot
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-(OIR) Outils et d'instruments de recherche (OIR) -1 -(de 7 001 $ à 150 000 $)
2016 - 2019

Le système ubiquitine dans la régulation des processus associés à l' ADN et le cancer

Lead researcher : El Bachir Affar
Funding sources: FRQS/Fonds de recherche du Québec - Santé (FRSQ)
Grant programs: PVXXXXXX-Bourse de chercheur-boursier : Senior
2016 - 2018

A microcalorimetry system to define the biochemical parameters of molecular interactions

Lead researcher : El Bachir Affar
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-(OIR) Outils et d'instruments de recherche (OIR) -1 -(de 7 001 $ à 150 000 $)
2011 - 2016

TRANSCRIPTIONAL REGULATION BY A NOVEL DEUBIQUITINASE MULTI-PROTEIN COMPLEX

Lead researcher : El Bachir Affar
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-(MSH) Bourses de nouveaux chercheurs
2011 - 2016

TRANSCRIPTIONAL REGULATION BY A NOVEL DEUBIQUITINASE MULTI-PROTEIN COMPLEX

Lead researcher : El Bachir Affar
2010 - 2016

ROLE OF THE DEUBIQUITINASE USP16 IN CELL CYCLE PROGRESSION

Lead researcher : El Bachir Affar
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
2011 - 2014

RÔLES DU SYSTÈME UBIQUITINE DANS LA TRANSCRIPTION ET LA RÉPARATION DE L'ADN

Lead researcher : El Bachir Affar
2009 - 2014

ROLE OF THE DEUBIQUITINASE USP16 IN CELL CYCLE PROGRESSION

Lead researcher : El Bachir Affar
2011

CHARACTERIZATION OF NOVEL EPIGENETIC MARKS

Lead researcher : El Bachir Affar
2010

MONITORING GENE FUNCTION AND REGULATION IN PHYSIO-PATHOLOGOCAL PROCESSES

Lead researcher : El Bachir Affar

Outreach

Autres activités et contributions

  • Membre de la Fondation du cancer du sein du Québec

Publications and presentations

Publications

Publications choisies

  • Daou, N Mashtalir, I Hammond-Martel, H Pak, H Yu, G Sui, TM. Kristie and EB Affar.  Crosstalk Between O-GlcNAcylation And Proteolytic Cleavage Regulates The HCF-1 Maturation Pathway. Proc Natl Acad Sci., 2011;108(7):2747-52
  • I Hammond-Martel, H Pak, H Yu, R Rouget, AA Horwitz, JD. Parvin, EA. Drobetsky and EB Affar. PI 3 Kinase Related Kinases-Independent Proteolysis of BRCA1 Regulates Rad51 Recruitment During Genotoxic Stress in Human Cells. PlosONE 10.1371/journal.pone.0014027 (2010).
  • H Yu, N Mashtalir, S Daou, I Hammond-Martel, J Ross, G Sui, GW. Hart, FJ Rauscher III, EA Drobetsky, E Milot, Y Shi and EB Affar. The Ubiquitin Carboxyl Hydrolase BAP1 Forms a Ternary Complex with YY1 and HCF-1 and is a Critical Regulator of Gene Expression.  Mol. Cell. Biol.30(21):5071-85, (2010). Raphael Rouget , Yannick Auclair, Martin Loignon, El Bachir Affar, Elliot Drobetsky. A sensitive flow cytometry-based nucleotide excision repair assay unexpectedly reveals that mitogen-activated protein kinase signalling does not regulate the removal of UV-induced DNA damage in human cells. Journal of Biological Chemistry, 283(9):5533-5541, (2008).
  • Andrew A. Horwitz, El Bachir Affar, George F. Heine, Yang shi, Jeffrey D. Parvin. A novel mechanism for transcriptional repression dependent on the BRCA1 E3 ubiquitin ligase. Proc. Natl. Acad. Sci., 104(16):6614-6619, (2007).
  • Yu May Ma, Emmanuel Boucrot, Judit Villen, El Bachir Affar, Steven P. Gygi, Heinrich G. Gottlinger and Tomas Kirchhausen. Targeting of AMSH to endosomes is required for EGF receptor degradation. Journal of Biological Chemistry, 282(13):9805-9812, (2007).
  • El Bachir Affar, Margaret Po-shan Luke, Frédérique Gay, Dominica Calvo, Guangchao Sui, Robert S. Weiss, En Li, and Yang Shi. Targeted Ablation of Par-4 Reveals a Cell-Type Specific Susceptibility To Apoptosis-Inducing Agents. Cancer Research, 66(7):3456-3462, (2006)
  • El Bachir Affar*, Frédérique Gay*, Yujiang Shi, Huifei Liu, Maite Huarte, Su Wu, Collins Tucker, En Li, and Yang Shi. Essential dosage-dependent functions of the transcription factor Yin Yang 1 in late embryonic development and cell cycle progression. Molecular and Cellular Biology, 26(9):3565-3581, (2006). * Equal Contribution.
  • Sang Ki Park, Minh Dang Nguyen, André Fisher, Margaret Po-Shan Luke, El Bachir Affar, Paul B. Dieffenbach, Huang-Chun Tseng, Yang Shi and Li-Huei Tsai. Par-4 links dopamine signaling and depression. Cell,122(2):275-287, (2005).
  • Guangchao Sui, El Bachir Affar*, Yujiang Shi*, Chrystelle Brignone, Nathan R. Wall, Peng Yin, Mary Donohoe, Dominica Calvo, Margaret P. Luke, Steven R. Grossman, Yang Shi. Yin Yang 1 is a negative regulator of p53. Cell, 117(7): 859-872, (2004). * Equal contribution.
  • Yujiang Shi, Jun-ichi Sawada, Guangchao Sui, El Bachir Affar, Johnathan R. Whetstine, Fei Lan, Hidesato Ogawa, Margaret Po-Shan Luke, Yoshihiro Nakatani and Yang Shi. Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature, 422(6933):735-738, (2003).
  • Guangchao Sui*, Christina Soohoo*, El Bachir Affar*, Frédérique Gay, Yujiang Shi, William Forrester and Yang Shi. A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc. Natl. Acad. Sci., 99:5515-5520, (2002). * Equal Contribution.
  • El Bachir Affar, Rashmi G. Shah, Annie K. Dallaire, Vincent Castonguay and Girish M. Shah. Role of poly(ADP-ribose) polymerase in rapid intracellular acidification induced by alkylating DNA damage. Proc. Natl. Acad. Sci., 99: 245-250, (2002).

Disciplines

  • Biochemistry
  • Immunology
  • Oncology
  • Molecular Biology

Areas of expertise

  • Cell Signaling and Cancer
  • Molecular Transportation
  • Cancer Genetics
  • Genes