Razqallah Hakem, PhD

Senior Scientist, Princess Margaret Cancer Centre
Keywords: BRCA1, BRCA2, tumour suppressors, DNA damage and repair, cell signalling, synthetic lethality, cancer

The focus of our research is to characterize novel genetic risk factors, and to unravel mechanisms that regulate cell signaling pathways important for human cancer. In addition, a major effort of our research program is to identify novel strategies that improve cancer therapy.

Currently ongoing projects:
1. BRCA1 and BRCA2 and their role in cancer
2. Role of signaling pathways (e.g. NOTCH, WNT and Hippo) in cancer
3. Crispr screening to identify targets to kill breast, ovarian and other tumor types

Using multidisciplinary approaches and collaborating with scientists, clinicians, pathologists and bioinformatics experts, we focus on our long-term goal “to contribute to better diagnosis and therapy for cancer patients”.
Ubiquitin ligase RNF8 suppresses Notch signaling to regulate mammary development and tumorigenesis.
J Clin Invest. 2018 Sep 17;:
Li L, Guturi KKN, Gautreau B, Patel PS, Saad A, Morii M, Mateo F, Palomero L, Barbour H, Gomez A, Ng D, Kotlyar M, Pastrello C, Jackson HW, Khokha R, Jurisica I, Affar EB, Raught B, Sanchez O, Alaoui-Jamali M, Pujana MA, Hakem A, Hakem R
The pseudokinase MLKL activates PAD4-dependent NET formation in necroptotic neutrophils.
Sci Signal. 2018 Sep 04;11(546):
D'Cruz AA, Speir M, Bliss-Moreau M, Dietrich S, Wang S, Chen AA, Gavillet M, Al-Obeidi A, Lawlor KE, Vince JE, Kelliher MA, Hakem R, Pasparakis M, Williams DA, Ericsson M, Croker BA
Reducing protein oxidation reverses lung fibrosis.
Nat Med. 2018 Jul 09;:
Anathy V, Lahue KG, Chapman DG, Chia SB, Casey DT, Aboushousha R, van der Velden JLJ, Elko E, Hoffman SM, McMillan DH, Jones JT, Nolin JD, Abdalla S, Schneider R, Seward DJ, Roberson EC, Liptak MD, Cousins ME, Butnor KJ, Taatjes DJ, Budd RC, Irvin CG,...
Preclinical evaluation of the selective small-molecule UBA1 inhibitor, TAK-243, in acute myeloid leukemia.
Leukemia. 2018 Jun 08;:
Barghout SH, Patel PS, Wang X, Xu GW, Kavanagh S, Halgas O, Zarabi SF, Gronda M, Hurren R, Jeyaraju DV, MacLean N, Brennan S, Hyer ML, Berger A, Traore T, Milhollen M, Smith AC, Minden MD, Pai EF, Hakem R, Schimmer AD
RNF168 and USP10 regulate topoisomerase IIα function via opposing effects on its ubiquitylation.
Nat Commun. 2016;7:12638
Guturi KK, Bohgaki M, Bohgaki T, Srikumar T, Ng D, Kumareswaran R, El Ghamrasni S, Jeon J, Patel P, Eldin MS, Bristow R, Cheung P, Stewart GS, Raught B, Hakem A, Hakem R
The Pseudokinase MLKL and the Kinase RIPK3 Have Distinct Roles in Autoimmune Disease Caused by Loss of Death-Receptor-Induced Apoptosis.
Immunity. 2016 Aug 10;
Alvarez-Diaz S, Dillon CP, Lalaoui N, Tanzer MC, Rodriguez DA, Lin A, Lebois M, Hakem R, Josefsson EC, O'Reilly LA, Silke J, Alexander WS, Green DR, Strasser A
Rad54 and Mus81 cooperation promotes DNA damage repair and restrains chromosome missegregation.
Oncogene. 2016 Feb 15;
Ghamrasni SE, Cardoso R, Li L, Guturi KK, Bjerregaard VA, Liu Y, Venkatesan S, Hande MP, Henderson JT, Sanchez O, Hickson ID, Hakem A, Hakem R
DICER1/Alu RNA dysmetabolism induces Caspase-8-mediated cell death in age-related macular degeneration.
Proc Natl Acad Sci U S A. 2014 Oct 27;
Kim Y, Tarallo V, Kerur N, Yasuma T, Gelfand BD, Bastos-Carvalho A, Hirano Y, Yasuma R, Mizutani T, Fowler BJ, Li S, Kaneko H, Bogdanovich S, Ambati BK, Hinton DR, Hauswirth WW, Hakem R, Wright C, Ambati J
Cooperation of Blm and Mus81 in development, fertility, genomic integrity and cancer suppression.
Oncogene. 2014 May 26;0
El Ghamrasni S, Cardoso R, Halaby MJ, Zeegers D, Harding S, Kumareswaran R, Yavorska T, Chami N, Jurisicova A, Sanchez O, Hande MP, Bristow R, Hakem R, Hakem A
The role of caspase-8 in amyloid-induced beta cell death in human and mouse islets.
Diabetologia. 2014 Apr;57(4):765-75
Park YJ, Woo M, Kieffer TJ, Hakem R, Safikhan N, Yang F, Ao Z, Warnock GL, Marzban L

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Senior Scientist, Princess Margaret Cancer Centre

Professor, Department of Medical Biophysics, University of Toronto
Professor, Department of Laboratory Medicine and Pathobiology, University of Toronto