Professor

Razq Hakem

PhD, University of Aix-Marseille II

Location
Princess Margaret Cancer Research Tower
Address
MaRS Centre , 101 College St., Rm 13-310, Toronto, Ontario Canada M5G 1L7
Research Interests
Cancer Diagnosis and Therapy, Cancer Mechanisms and Models

At a Glance

  • Identification of novel cancer genetic risk factors and diagnosis markers.
  • Dissect the cancer cell signaling mechanisms.
  • Multidisciplinary approach to cancer research.
  • Integration of multiomics, CRISPR-Cas9 screening, biochemistry, and molecular biology
  • Focus on discovering novel therapeutic options for patients with high-risk cancers

Short Bio

Dr. Hakem is a Professor at the Department of Medical Biophysics at the University of Toronto. He is also a Senior Scientist at the Princess Margaret Cancer Centre. He received his Ph.D from the University of Aix-Marseille II, France. He completed his post-doctoral training at the 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 his research program on identification of cancer mechanisms and discovering better therapeutic strategies for cancer.

Dr. Hakem’s laboratory has identified several novel tumor suppressor genes and extensively investigated their functions and how their loss or mutations promote cancer development. 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, Nature Genetics, Nature Communications, and The Journal of Clinical Investigation.

Dr. Hakem is well funded, and he is committed to providing excellent supervision and training to his students to allow them to be the next generation of Scientists. Several former trainees in the Hakem lab are now faculty members in top universities or have influential positions in the private sector.

Dr. Hakem is interested in supervising students who are highly self-motivated, interested in making discoveries, and committed to cancer research to help patients.


Research Synopsis

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

Currently ongoing projects investigate

1- BRCA1 and BRCA2 and their role in cancer

2- Signaling pathways including NOTCH, WNT and the Hippo pathways

3- CRISPR screening to identify synthetic lethal targets to kill breast, ovarian, and other tumor types

Using multidisciplinary approaches and collaborating with scientists, clinicians, pathologists and bioinformaticians, we focus on our long-term goal to contribute to better diagnosis and therapy for cancer patients.


Recent Publications

  • Patel, P., Abraham, K.J., Guturi, K.N., Khan, Z., Ho, B., Mateo, F., Palomero, L., Halaby, M.J., El Ghamransi, S., Barbour, H., Pujana, M.A., Brown, G., Affar, E.B., Mekhail, K., Hakem, A. and Hakem, R. (2021). RNF168 loss confers synthetic lethality in BRCA-deficient tumors through impairment of R-loop resolution. Journal of Clinical Investigation. doi: doi.org/10.1172/JCI140105
  • 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. (2018). Ubiquitin ligase RNF8 suppresses Notch signaling to regulate mammary development and tumorigenesis. Journal of Clinical Investigation. doi.org/10.1172/JCI120401
  • 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 IIa function via opposing effects on its ubiquitylation. Nature Communications. DOI: doi.org/10.1038/ncomms12638
  • Bohgaki M, Bohgaki M, Srikumar T, Maire G, Panier S, Stewart G, Raught R, Hakem A and Hakem R. (2013). RNF168 Ubiquitylates 53BP1 and Controls Its Responses to DNA Double-Strand Breaks. Proceedings of the National Academy of Sciences of the United States of America. DOI: doi.org/10.1073/pnas.1320302111
  • 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.
  • 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.
  • 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.
  • Hakem, R., Hakem, A., Duncan, G. S., Henderson, J. T., Woo, M., Soengas, M. S., Elia, A., de la Pompa, et al. (1998). Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell, 94: 339-352.
  • Hakem, R., de la Pompa, J.L., Sirard, C., et al. (1996). The tumor suppressor Brca1 is required for embryonic cellular proliferation in the mouse. Cell, 85: 1009-1023.

Honours and Awards

  • Dr. Hakem’s research is supported by the Lee K. and Margaret Lau Chair in Breast Cancer Research, a joint project between the University of Toronto and the Princess Margaret Hospital
  • Dr. Hakem is also a recipient of the prestigious Foundation Scheme grant/award from the Canadian Institutes for Health Research