ProfessorPhD, University of Aix-Marseille II
Princess Margaret Cancer Research Tower
101 College St., Rm 13-310
Toronto, Ontario M5G 1L7
Phone: (416) 634-8780
Lab Phone: (416) 634-8781
Email Dr. Razq Hakem
At A Glance:
- The focus of our research is to characterize novel genetic risk factors, cell signaling and molecular oncology mechanisms.
- We are particularly interested in studying the DNA damage response, NOTCH, WNT, and the HIPPO signaling pathways and their role in cancer.
- Cancer genetics and biochemistry are fundamental to our research.
- Our research is multidisciplinary with a long-term goal to discover better diagnosis tools and therapy for cancer patients.
Dr. Hakem is a Senior Scientist at the Princess Margaret Cancer Centre and a Professor at the Department of Medical Biophysics at the University of Toronto. He received his Ph.D degree from the University of Aix-Marseille II, France. He completed post-doctoral training at Howard Hughes Medical Institute/Washington University Medical School, Saint Louis in the US and the Amgen Research Institute in Toronto. Dr. Hakem started his faculty position in 1998 and has focused the research of his laboratory on cancer mechanisms. Using cancer genetics he has identified novel tumor suppressor genes (e.g. RNF8, MUS81 and PIRH2) and has also investigated the mechanisms of function and regulation of some major human tumor suppressor genes (e.g. BRCA1 and P53). Dr. Hakem is a world-class expert in cancer genetics, cell signaling and molecular oncology. His work has been published in leading journals including Cell, Science and The Journal of Experimental Medicine. Several of his former trainees have faculty positions or influential jobs in the private sectors.
The focus of our research is to characterize novel genetic risk factors, cell signaling and molecular oncology mechanisms that drive development and progression of human cancer. We also aim to identify novel strategies to improve cancer therapy. Deregulation of cell signaling pathways not only impairs development and differentiation; it also frequently drives the development of human cancers. Therefore, our laboratory is investigating the role in cancer of different key siganling pathways including the DNA damage response, NOTCH, WNT, and the HIPPO pathways. Cancer genetics and biochemistry are fundamental to our research. Mouse models, murine and human tumor lines that we have generated, and biopsies from cancer patients are being employed to conduct our studies. Using a multidisciplinary approach that involves scientists, clinicians, pathologists and bioinformatics experts we work towards our long-term goal of contributing to better diagnosis and therapy for cancer patients.
List of Key Publications:
Hakem, R., de la Pompa, J.L., Sirard, C., Mo, R., Woo, M., Hakem, A., Wakeham, A., Potter, J., Reitmair, A,. Billia., F., Firpo, E., Hui, C.C., Roberts, J., Rossant, J., and Mak, T.W. (1996). The tumor suppressor Brca1 is required for embryonic cellular proliferation in the mouse. Cell, 85: 1009-1023.
McPherson, J. P., Lemmers, B., Chahwan, R., Pamidi, A., Migon, E., Matysiak-Zablocki, E., Moynahan, M. E., Essers, J., Hanada, K., Poonepalli, A., Sanchez-Sweatman, O., Khokha, R., Kanaar, R., Jasin, M., Hande, M. P., and Hakem, R. (2004). Involvement of mammalian Mus81 in genome integrity and tumor suppression. Science, 304: 1822-1826.
McPherson, J. P., Lemmers, B., Hirao, A., Hakem, A., Abraham, J., Migon, E., Matysiak-Zablocki, E., Tamblyn, L., Sanchez-Sweatman, O., Khokha, R., Squire, J., Hande, M. P., Mak, T. W., and Hakem, R. (2004). Collaboration of Brca1 and Chk2 in tumorigenesis. Genes & Dev, 18: 1144-1153.
Salmena, L. and Hakem, R. (2005). Caspase-8 deficiency in T cells leads to a lethal lymphoinfiltrative immune disorder. The Journal of Experimental Medicine, 202: 727-732.
Li, L., Halaby, M. J., Hakem, A., Cardoso, R., El Ghamrasni, S., Harding, S., Chan, N., Bristow, R., Sanchez, O., Durocher, D., Hakem, R. (2010). Rnf8 deficiency impairs class switch recombination, spermatogenesis, genomic integrity and predisposes for cancer. The Journal of Experimental Medicine. 207:983-97
Bohgaki, T., Bohgaki, M., Cardoso, R., Panier, S., Stewart, G.S., Sanchez, O., Durocher, D., Hakem, A. and Hakem, R. (2011). Genomic instability, defective spermatogenesis, immunodeficiency and cancer in a mouse model of the RIDDLE syndrome. PLoS Genet. April; 7(4): e1001381
Hakem, A., Bohgaki, M., Lemmers, B., Tai, E., Leonardo Salmena, L., Elzbieta Matysiak-Zablocki, E., Bähr, W. I. L., Karaskova, J., Boutros, P, Sheng, Y., Arrowsmith, C., Chesi, M., Bergsagel P. L., Perez-Ordonez, B., Squire, J., Jurisica, I., Penn, L., Sanchez, O., Benchimol, S. & Hakem, R. (2011). Pirh2 is a critical negative regulator balancing opposing p53 and c-Myc induced oncogenic pathways. PLoS Genet. Nov;7(11): e1002360.
Bohgaki, T., Salmena, L., Matysiak-Zablocki, E., Bohgaki, M., Sanchez, O., Strasser, A., Hakem, A. and Hakem, R. (2011). Caspase-8 Inactivation in T-cells Increases Necroptosis and Suppresses Autoimmunity Associated with Bim Deficiency. The Journal of Cell Biology. 195(2):277-91.
Hakem, A., El Ghamrasni, S., Maire, G., Lemmers, B., Salmena, L., Karaskova, J., Perez-Ordonez, B., Sanchez, O., Squire, J. and Hakem, R. (2012). Role of Casp8 in Cytokinesis, Genomic Integrity and Cancer. Blood. 119, p3495.
Halaby MJ, Hakem A, Li L, El Ghamrasni S, Venkatesan S, Hande P, Sanchez O and Hakem R. Synergistic interaction of Rnf8 and p53 in the protection against genomic instability and tumorigenesis. (2013). PLoS Genet. 2013;9(1):e1003259.
Bohgaki M, Bohgaki M, Srikumar T, Maire G, Panier S, Stewart G, Raught R, Hakem A and Hakem R. RNF168 Ubiquitylates 53BP1 and Controls Its Responses to DNA Double-Strand Breaks. (2013). PNAS 110(52):20982-7.
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. Cooperation of Blm and Mus81 in development, fertility, genomic integrity and cancer suppression. (2015). Oncogene. 34(14):1780-9.
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. (2016). Rad54 and Mus81 cooperation promotes DNA damage repair and restrains chromosome missegregation. Oncogene 35(37):4836-45.
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. (2016). RNF168 and USP10 regulate topoisomerase IIα function via opposing effects on its ubiquitylation. Nat. Commun. 7:12638
- Parasvi Patel