El Bachir Affar

TITLE

• Assistant Professor, Medicine Department, Université de 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.

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.

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RESEARCH TEAM

Ph.D. Students:

• Ian hammond-Martel
• Helen Yu
• Salima Daou
• Nazar Mashtalir

M.Sc. Student:

• Helen Pak

Technician:

• Diana Adjaoud

Selected papers

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).

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).

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)

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