El Bachir Affar

Office Phone: 514-252-3400 ext. 3343
Fax: 514-252-3430
Lab Phone: 514-252-3400 ext. 4683
el.bachir.affar@umontreal.ca

Research Axis  Immunology-Oncology
Research Unit  Cellular Signaling and Cancer

TITLE

  • Associate Professor, Medicine Department, Université de Montréal. 
  • Accreditation in the Department of Biochemistry, University of Montréal.
  • Accreditation in the Biomedical Sciences Program, University of Montréal.
  • Accreditation in the Molecular Biology Program, University of Montréal.

EDUCATION

  • Ph.D., Physiology-Endocrinology, Laval University Hospital Centre (CHUL), Quebec City, 1995-1999.
  • Postdoctorate, Skin Cancer Research Laboratory, Laval University Hospital Centre (CHUL), Quebec City, 1999-2000.
  • Postdoctorate, Department of Pathology, Harvard Medical School, Boston, USA, 2000-2006.

DISTINCTIONS AND ACHIEVEMENTS

  • CIHR, New Researcher Grant.
  • Junior Investigator Grant 2, FRSQ (Le Fonds de la recherche en santé du Québec) .
  • Taplin Grant, Harvard University.
  • Institute of Genetics Maud Menten New Principal Investigator Finalist Prize, CIHR (2011).
  • Honor table of the Dean (PhD), Laval University, Canada (1999)

RESEARCH INTERESTS

  • Cellular signaling through ubiquitination;
  • DNA-dependent Processes (DNA transcription and repair);
  • Molecular basis of cancer.

Ubiquitination is a reversible, covalent post-translational modification that regulates protein function and as such plays crucial roles in a wide range of physiological processes. Importantly, gain- or loss-of-function mutations in components of the ubiquitin system have been causally linked to tumorigenesis. The reverse reaction of ubiquitination is catalyzed by deubiquitinases (DUBs), a family of enzymes that removes ubiquitin from proteins. The cellular roles of DUBs are currently very poorly understood, although these enzymes are clearly emerging as critical components of the ubiquitin system. A long-term goal of our research program is to delineate the roles of DUBs in DNA-dependent processes (e.g. transcription and DNA damage/repair) and cancer development. In this regard, the deubiquitinase BAP1 is of particular interest, as it represents the only member of its family which is predominantly localized in the nucleus. Moreover there are strong indications that BAP1 is a critical determinant in the maintenance of genomic stability and in multistage carcinogenesis, since this DUB was initially identified as a BRCA1 tumor suppressor-interacting protein, and subsequently shown to be mutated in lung and breast cancers.
To delineate the biological function and mechanism of action of BAP1 as well as other DUBs, we use a combination of techniques and approaches. These include biochemistry, molecular biology, mammalian cell culture systems and mouse genetics. We hope that new insight will be provided into the role of deubiquitination in cell signaling and neoplastic transformation.

Top 

RESEARCH TEAM

Ph.D. Students:

  • Salima Daou
  • Haithem Barbour
    • Bourse d’excellence du gouvernement  tunisien 2013-2017
    • Cole Foundation Scholarship 2014-2016
  • Nadine Sen 
    • FRSQ Scholarship 2014-2017
    • Cole Foundation Scholarship 2014-2016
    • Bourse de recutement de la faculté de médecine 2014
  • Louis Masclef

    M.Sc. Student:

    •  Oumaima Ahmed
      • Bourse de la francophonie

    Trainee:

    •  Saad Mengaad

      Technician:

      • Diana Adjaoud

      Selected papers

      Mashtalir N, Daou S, Barbour H, Sen NN, Gagnon J, Hammond-Martel I, Dar HH, Therrien M, Affar el B, Autodeubiquitination Protects the Tumor Suppressor BAP1 from Cytoplasmic Sequestration Mediated by the Atypical Ubiquitin Ligase UBE2O. Mol Cell. 2014 May 8;54(3):392-406.

      Yu H, Pak H, Hammond-Martel I, Ghram M, Rodrigue A, Daou S, Barbour H, Corbeil L, Hébert J, Drobetsky E, Masson JY, Di Noia JM, Affar el B, Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair. Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):285-90.

      S 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).

      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).

      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.

      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).

      Complete list of Dr Affar’s publications (PubMed)

      ADDITIONAL INFORMATION

      Grants

      • Canadian Institutes of Health Research (CIHR)
      • The Cancer Research Society (CRS)
      • The Natural Sciences and Engineering Research Council of Canada (NSERC)
      • The Canadian Cancer Society Research Institute (CCSRI)
      • The Leukemia & Lymphoma Society of Canada

      Top