Title:   
Full Professor

Institute:
University Health Network, Toronto

Department:  
Research

Province:
Ontario

Training:  
Postdoctoral fellow, Amgen Research Institute, University of Toronto, Ontario
Postdoctoral fellow, HHMI, Washington University Medical School, Saint Louis, MO, USA
Ph.D., Immunology, University Aix-Marseille II, Marseille, France

Research interests:
DNA damage repair
Cell death mechanisms
Cancer

Career highlights:
Demonstration of the importance of Brca1 in development and the role p53 and Chk2 play in suppressing breast cancer associated with Brca1 mutations; Demonstrated the role the E3 ligases Rnf8 and Rnf168 in suppressing immunodeficiency and cancer; Other mouse models generated include caspase 3-/-, caspase 9-/-, caspase 8-/-, Mus81-/-, Lats2-/-, bclaf1-/-, caspase 8-/- and Pirh2-/- mice.

Research Projects

Project title:
Analysis of the cooperation of p53 with RNF8 and RNF168 in suppressing genomic instability and cancer

Funding period:  
2010-2012

Program:
Operating Grant (Basic Research)

Summary:
P53 is the most important protein that functions as a safeguard against tumor development. It is also the most frequently inactivated protein in human cancer. However, p53 functions with other proteins and has been shown to cooperate in cancer suppression with a number of proteins important for the signaling and repair of DNA damage. Recent studies identified RNF8 and RNF168 as essential factors for DNA damage signaling and repair. We have generated mice lacking either RNF8 or RNF168 and observed that they have elevated level of p53. These mice also carry increased level of chromosomal abberations, a hallmark of increased cancer risk. Interestingly, our data has already confirmed that RNF8 mice are highly predisposed for tumorigenesis. We will examine the effect of p53 inactivation on tumorigenesis of mice lacking either RNF8 or RNF168. We will also examine whether the expression of RNF8 and RNF168 is affected in human tumors and will evaluate the responses of human tumors deficient for RNF8 and RNF168 to radiation and chemotherapeutic drugs.

CRS publications:

Bohgaki, T., Bohgaki, M., Cardoso, R., Panier, S., Stewart, G.S., Sanchez, O., Durocher, D., Hakem, A. and Hakem, R. Genomic instability, defective spermatogenesis, immunodeficiency and cancer in a mouse model of the RIDDLE syndrome. PLoS Genet. 2011 April; 7(4): e1001381

Past CRS projects:

2007 Functional Interactions Between BRCA1 and PUMA in Apoptosis, Genomic Stability and Cancer
 
2004 Analysis of the role of Eme2 (essential meiotic endonuclease 2) in DNA repair and cancer