With a PhD in physiology and endocrinology, El Bachir Affar heads the Cell Signalling and Cancer Research Unit at Hôpital Maisonneuve-Rosemont. He is also a full professor in the Faculty of Medicine and an adjunct professor in the Department of Biochemistry and Molecular Medicine at Université de Montréal.
El Bachir Affar is interested in cellular signalling via ubiquitination, DNA- and chromatin-dependent processes (DNA transcription and repair), and the molecular bases of cancer. His team works in particular on the BAP1 gene, which frequently mutates in some types of cancers.
Cellular Signalling and Cancer
Ubiquitination is a post-translational modification that plays a key role in regulating a number of cellular functions. Clinically speaking, the mutations of many genes in the ubiquitin system have been causally linked to various diseases, including cancer. Ubiquitination is a reversible process due to the presence of deubiquitinating enzymes, or enzymes that specifically remove ubiquitin from target proteins. Although deubiquitinating enzymes are not well understood, they are nevertheless emerging as central regulators in the ubiquitin system.
Our goal is to characterize the biological functions and mechanisms of action of the deubiquitinating enzymes involved in DNA transcription and repair, two processes whose deregulation plays a key role in the development of cancer.
We use state-of-the-art biochemistry, molecular biology, and cell culture approaches to characterize the functions of deubiquitinating enzymes. Our work provides a better understanding of the molecular mechanisms governing the ubiquitin system. New concepts may also be developed with regard to the regulation of DNA transcription and repair.
Our work should also help identify new therapeutic targets to treat cancer with personalized medicine.
PublicationsVoir toutes les publications
Monoubiquitination of ASXLs controls the deubiquitinase activity of the tumor suppressor BAP1.Daou S, Barbour H, Ahmed O, Masclef L, Baril C, Sen Nkwe N, Tchelougou D, Uriarte M, Bonneil E, Ceccarelli D, Mashtalir N, Tanji M, Masson JY, Thibault P, Sicheri F, Yang H, Carbone M, Therrien M, Affar EB.Nat Commun. 2018 Oct 22;9(1):4385. doi: 10.1038/s41467-018-06854-2.
BAP1 regulates different mechanisms of cell death. Affar EB, Carbone M. Cell Death Dis. 2018 Nov 19;9(12):1151. doi: 10.1038/s41419-018-1206-5.
BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation. Bononi A, Giorgi C, Patergnani S, Larson D, Verbruggen K, Tanji M, Pellegrini L, Signorato V, Olivetto F, Pastorino S, Nasu M, Napolitano A, Gaudino G, Morris P, Sakamoto G, Ferris LK, Danese A, Raimondi A, Tacchetti C, Kuchay S, Pass HI, Affar EB, Yang H, Pinton P, Carbone M. Nature. 2017 Jun 22;546(7659):549-553.
The BAP1/ASXL2 Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer. Daou S, Hammond-Martel I, Mashtalir N, Barbour H, Gagnon J, Iannantuono NV, Nkwe NS, Motorina A, Pak H, Yu H, Wurtele H, Milot E, Mallette FA, Carbone M, Affar el B .J Biol Chem. 2015 Nov 27;290(48):28643-63.
Undetectable histone O-GlcNAcylation in mammalian cells. Gagnon J, Daou S, Zamorano N, Iannantuono NV, Hammond-Martel I, Mashtalir N, Bonneil E, Wurtele H, Thibault P, Affar el B. Epigenetics. 2015;10(8):677-91.
Autodeubiquitination protects the tumor suppressor BAP1 from cytoplasmic sequestration mediated by the atypical ubiquitin ligase UBE2O. Mashtalir N, Daou S, Barbour H, Sen NN, Gagnon J, Hammond-Martel I, Dar HH, Therrien M, Affar el B. Mol Cell. 2014 May 8;54(3):392-406.
Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair. 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. Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):285-90.
Roles of ubiquitin signaling in transcription regulation. Hammond-Martel I, Yu H, Affar el B. Cell Signal. 2012 Feb;24(2):410-21.
Crosstalk between O-GlcNAcylation and proteolytic cleavage regulates the host cell factor-1 maturation pathway. Daou S, Mashtalir N, Hammond-Martel I, Pak H, Yu H, Sui G, Vogel JL, Kristie TM, Affar el B. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2747-52.
The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1 and is a critical regulator of gene expression. Yu H, Mashtalir N, Daou S, Hammond-Martel I, Ross J, Sui G, Hart GW, Rauscher FJ 3rd, Drobetsky E, Milot E, Shi Y, Affar el B. Mol Cell Biol. 2010 Nov;30(21):5071-85.
Department of Pathology, Harvard Medical School, Boston
Skin Cancer Research Laboratory, Centre hospitalier de l'Université Laval (CHUL), Québec City
PhD in physiology and endocrinology
Centre hospitalier de l'Université Laval (CHUL), Québec City
- 2016 Senior Research Scholar (FRQS)
- 2011 New Investigator Award (CIHR)
- 2011 Junior 2 Research Scholar (FRQS)
- 2011 Finalist for the Maud Menten New Principal Investigator Prize (Institute of Genetics, CIHR)
- 2007 Junior 1 Research Scholar (FRQS)
- 2001 Taplin Postdoctoral Fellowship (Harvard University, Boston)
- 1999 Dean’s Honour List – PhD (Université Laval)
- 1991 Award of excellence for graduate studies (Ministry of National Education, Morocco)