Samuel Benchimol

PhD (Toronto)
Professor, Department of Biology
Research Interests:   p53 Tumour Suppressor Gene, Apoptosis, Senescence, Cancer and Progeria

Research Focus

The p53 tumour suppressor gene represents the most common target for mutational inactivation in human cancer. At the cellular level, p53 protein regulates cell cycle progression, senescence, apoptosis and various metabolic processes. p53 is a sequence-specific DNA-binding transcription factor. In response to abnormal proliferative signals and many stress signals including DNA damage, p53 protein is stabilized and activated through a succession of post-translational modifications including phosphorylation and acetylation. Once activated, p53 regulates the expression of a number of target coding genes and non-coding RNAs that collectively contribute to p53-dependent cellular responses. p53 protein can induce cells to undergo a transient arrest in the G1 phase of the cell cycle that is believed to allow time for repair of damaged DNA before the initiation of S phase. Activated p53 can also eliminate cells through mechanisms that involve prolonged arrest in G1 (senescence) or apoptosis. The elimination of damaged, stressed or abnormally proliferating cells by p53 is considered to be the principal means by which p53 mediates tumour suppression. My research program is directed at understanding how the p53 protein regulates cell growth and suppresses tumorigenesis. There are 3 ongoing projects: (i) Understanding how cytokines block p53-dependent apoptosis; (ii) evaluating the role of p53 as a determinant of chemosensitivity in cancer cells; and (iii) investigating the pathway that leads to p53 activation in replicative senescence and premature senescence.

Representative  Publications:

Wheaton K, Campuzano D, Ma W, Sheinis M, Ho B, Brown G and Benchimol S. (2016). Premature senescence in Hutchinson Gilford Progeria Syndrome (HGPS) cells results from p53 activation in response to replication stress. Submitted

Kim SS and Benchimol S. (2013). HDAC5 – A critical player in the p53 acetylation network. Mol. Cell 52: 289-290.

Begashev A, Fan S, Mukerjee R, Claudio PP, Chabrashvili T, Leng RP, Benchimol S and Sawaya BE. (2013). Cdk9 phosphorylates Pirh2 protein and prevents degradation of p53 protein. Cell Cycle 12: 1569-1577.

Nuaaman MM*, Benchimol S. (2013). Proteasome-independent p53 protein degradation. Cell Research 23: 597-598.

Ma W, Lin Y, Xuan W, Iversen PL, Smith LJ, Benchimol S. (2012). Inhibition of p53 expression by peptide-conjugated phosphorodiamidate morpholino oligomers sensitizes human cancer cells to chemotherapeutic drugs. Oncogene 21: 1024-1033.

Assaily W, Rubinger DA, Wheaton K, Lin Y, Ma W, Xuan W, Brown-Endres L, Tsuchihara K, Mak TW and Benchimol S. (2011). ROS-mediated p53 induction of Lpin1 regulates fatty acid oxidation in response to nutritional stress. Mol. Cell 44: 491-501.

Hakem A, Bohgaki M, Lemmers B, Tai E, Salmena L, Matysiak-Zablocki E, Jung YS, Karaskova J, Kaustov L, Duan S, Madore J, Boutros P, Sheng Y, Chesi M, Bergsagel PL, Perez-Ordonez B, Mes-Masson AM, Penn L, Squire J, Chen X, Jurisica I, Arrowsmith C, Sanchez O, Benchimol S and Hakem R. (2011). Role of Pirh2 in mediating the regulation of p53 and c-Myc. PLoS Genet. November 7(11): e1002360.

Wheaton K, Muir J, Ma W and Benchimol S. (2010). BTG2 antagonizes Pin1 in response to mitogens and telomere disruption during replicative senescence. Aging Cell 9: 747-760.