Alain Nepveu, PhD
Research Institute of the McGill University Health Centre
Regular Member Cancer
McGill University Health Centre (MUHC)
Departments of Oncology, Biochemistry and Medicine
My research focuses on the regulation of transcription in mammalian cells and, in particular, the roles of transcription factors in DNA repair and DNA damage responses. We combine a vast array of molecular biology and functional genomic approaches together with tissue culture and mouse models to investigate how alterations in DNA repair and DNA damage responses contribute to the initiation and progression of cancer. It is generally accepted that defects in DNA repair, whether transient or permanent, contribute to tumor development and progression. Yet, to replicate their DNA and proliferate, cancer cells need DNA repair mechanisms, perhaps even more than do normal cells. We study how defects in DNA repair can contribute to tumor initiation and how certain cancer cells become dependent on specific DNA repair pathways. The goal of our work is to use the acquired knowledge to exploit the sensitivity of cancer cells to specific radiotherapeutic and chemotherapeutic treatments.
- the role Cut repeat domains in base excision repair.
- DNA repair capability of cancer cells and resistance to chemo- and radio-therapy.
- epithelial-to mesenchymal transition of cancer cells and DNA repair properties.
- DNA repair functions of a haploinsufficient tumor suppressor.
- regulation of the spindle assembly checkpoint during mitosis and promotion of genomic instability.
Cancer, molecular biology, functional genomics, DNA repair
Sansregret, L., J. Livingstone, C. Vadnais, N. Kwiatkowski, A. Awan, C. Cadieux, L. Leduy, M. Hallett, and Alain Nepveu. CUX1 causes chromosomal instability by promoting bipolar divisions after mitotic failure. Proceedings of the National Academy of Sciences of the USA, 108(5):1949-1954. 2011.
Vadnais, C., S. Davoudi, M. Afshin, R. Harada, R. Dudley, P.-L. Clermont, E. Drobetsky and Alain Nepveu. CUX1 Transcription Factor is Required for Optimal ATM/ATR-Mediated Responses to DNA Damage. Nucleic Acids Research, Feb 8, 2012: 1-13. 2012.
Vadnais, C., A. A. Awan, L. Leduy, G. Bérubé, and Alain Nepveu. Long-Range Transcriptional Regulation by the p110 CUX1 Homeodomain Protein on the ENCODE Array. BMC Genomics. http://www.biomedcentral.com/1471-2164/14/258. 2013.
Cadieux, C., V. Kedinger, L. Yao, M. Drossos, M. Paquet, and A. Nepveu. MMTV-p75 and p110 CUX1 Transgenic Mice Develop Mammary Tumors of Various Histological Types. Cancer Research, 69: 7188-7197. 2009.
Sansregret, L., D. Gallo, M. Santaguida, L. Leduy, M. Hallett, and Alain Nepveu. Hyperphosphorylation by Cyclin B/CDK1 in Mitosis Resets CUX1 DNA Binding Clock at Each Cell Cycle. Journal of Biological Chemistry, 285(43):32834-32843. 2010.