Discover novel functions of the polycomb group proteins ASXLs in epigenetic regulation

Subject of the thesis: Biochemical and Functional Characterization of ASXLs and interacting partners: implications for chromatin-associated processes, cell cycle control and tumor suppression.

Our research delves into the complex mechanisms of epigenetic regulation, particularly in relation to Polycomb Group proteins. Central to our study are the ASXL proteins, key players in epigenetic regulation. Despite their significance, much remains to be discovered about how ASXL proteins contribute to epigenetic regulations and how their deregulation influences cancer and other diseases. By employing advanced genomics, bioinformatics, proteomics and mouse genetics methodologies, including CRISPR/Cas technology, we aim to uncover the roles and mechanisms of ASXL proteins in epigenetic regulation. For students who become part of our team, this project is a great learning opportunity at the forefront of Proteomics, Genomics, and cell signaling.

Financing : The annual salary for a PhD student is $26,000 and the HMR research center offers competitive scholarship competition (20K to 30K)for Ph.D students with outstanding academic achievements

In our laboratory, we've cultivated an environment that is not only convivial and welcoming but also firmly committed to Excellence, Diversity, Inclusion, and Accessibility (EDIA) principles. The ambiance in the lab is friendly and supportive, fostering a sense of community and collaboration among all members. The lab has currently 6 PhD students, and 3 undergraduate students.

We provide ample resources and support to facilitate cutting-edge research. This includes access to state-of-the-art equipment, close supervision and a network of collaborators. Our lab is a place where the endeavors for extraordinary research and accomplishments are encouraged.

https://www.umontreal.ca/
https://pubmed.ncbi.nlm.nih.gov/?term=El%2C+Affar

Selected publications :

Polycomb group-mediated histone H2A monoubiquitination in epigenome regulation and nuclear processes. Barbour H, Daou S, Hendzel M and  Affar EB. Nat Commun. 2020; 11: 5947

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.

Candidates should have a training in molecular biology or biochemistry or a related discipline (cell biology), have excellent organizational skills, and a strong interest in cell signaling and molecular oncology. A strong emphasis is put towards hard work and scientific discovery.
Bilingual scientific and social environment. French or English speaking students are encouraged to apply.

The PhD duration is usually 4 to 5 years in Canada