Dr. Philippe Gros
Rosalind and Morris Goodman Cancer Research Centre
Departments of Biochemistry, Medicine and Oncology
1. James McGill Professorship from McGill University, 2003-2010
2. Fellow, Academy of Sciences, Life Science Division, Discipline of Molecular Biology and Genetics, The Royal Society of Canada, 2003
3. Queen Elizabeth II Diamond Jubilee Medal - Association of Universities and Colleges of Canada, The Governor General of Canada, 2013
Dr. Gros’ research focuses on the genetic and molecular mechanisms of pathways involved in the development of drug resistance and the genetic determinants involved in pre-disposition to cancer. His research program is divided into two main areas:
1) Multidrug resistance: Dr. Gros’ laboratory has worked for many years on the phenomenon of multidrug resistance in tumor cells, as caused by members of the P-glycoprotein (MDR) and multidrug resistance associated protein (MRP) family. More recently, his team has studied resistance to two groups of drugs that are used in the treatment of multiple myeloma, namely the nucleoside analog arabinocytosine (cytarabine), and the proteasome inhibitor Bortezomib (Valcade). They are currently studying the mechanism by which Bortezomib induces cell death via formation of stress granules, and activation of programmed cell death, and how Bortezomib resistant cell lines developed in Dr. Gros’ laboratory can survive these effects of the drug.
2) Genetic determinants involved in pre-disposition to cancer. In this new project, Dr. Gros’ team used chemical carcinogenesis with azoxymethane (AOM) to induce colorectal tumors in mice. They have screened several inbred strains of mice for differences in susceptibility to colorectal cancer induced by AOM, measured by the type, number and size of lesions detected in the colon. In this assay, A/J mice are susceptible while C57BL/6J mice are highly resistant. Using a unique set of AcB/BcA recombinant congenic mouse lines, they have determined that the genetic basis for this difference in susceptibility is caused by a single major locus, that they have named Ccs3.
The locus maps on chromosome 3, and the minimal genetic and physical interval for this region contains an estimated ~50 genes. These genes are currently being investigated for their pattern of tissue and cell-specific expression, and for the presence of mutations in either normal tissues or in DNA from tumors emerging in susceptible animals. They are also interrogating human primary tumor samples for alterations in human homologues of the mouse genes present in the Ccs3 interval.
Finally, they have developed a model of inflammation-induced colorectal cancer, induced by dextran sulfate and AOM. They are investigating the genetic basis of differential susceptibility of inbred mouse strains to colorectal tumors induced by this treatment.