Title: 
Research Unit Director and Research Associate Professor

Institute:
Institut de recherches cliniques de Montréal

Department: 
Molecular Virology Laboratory

Province:
Quebec

Training:
Postdoctoral Fellow, Banting and Best Department of Medical Research (BBDMR), University of Toronto, Toronto, Ontario
PhD, Molecular and Medical Genetics, University of Toronto, Toronto, Ontario
BSc, Biochemistry, Université de Montréal, Montreal, Quebec

Research interests:
Cancer/Oncology; Virology; Molecular and Cellular Biology

Career highlights:
Discovery of host factors regulating papillomavirus genome replication and transcription; Discovery of the first small molecule inhibitors of papillomavirus genome replication; Discovery of the Fcp1 (CTDPI) phosphatase that dephosphorylates RNA polymerase II.

Research Projects

Project title: 
Small molecule inhibitors of HPV E6-mediated degradation of P53

Funding period:
2011-2013

Program:
Operating Grant (Basic Research)

Summary:
Infection with human papillomaviruses (HPV) is associated with the development of several cancers, including cervical and anal cancer as well as a subset of head-and-neck cancers. Although vaccines and screening programs are available to prevent and detect pre-cancerous and cancerous lesions caused by HPV, no antiviral treatment is currently available for already infected patients. The proposed study aims to identify new avenues for treating HPV-associated cancers, by interfering with the E6 protein of the virus. E6 abrogates the function of p53, a cellular protein that prevents uncontrolled cell division, and hence, cancer. Our initial studies have suggested that this carcinogenic effect of E6 requires the cellular protein Aurora A. We propose to clarify the role of Aurora A for the function of E6 and to evaluate the effect of inhibitors/drugs that target Aurora A on the growth of HPV-containing cancer cells. It is our hope that these studies will help validate the use of upcoming drugs that target Aurora A for the treatment of HPV-associated cancers.

CRS publications:

Sénéchal, H., K. Sellin, G. G. Poirier, B. Coulombe, L. A. Laimins and J. Archambault. Amino acid substitutions that specifically impair the transcriptional activity of human papillomavirus E2 affect binding to the long isoform of Brd4, Virology, 358(1):10-17, 2007.

Fradet-Turcotte, A. and J. Archambault. Recent advances in the search for antiviral agents against human papillomaviruses, Antiviral Therapy, 12(4): 431-451, 2007. (Invited review)

Gagnon, D., S. Joubert, H. Sénéchal, A. Fradet-Turcotte, S. Torre, and J. Archambault. Proteasomal degradation of the papillomavirus E2 protein is inhibited by overexpression of bromodomain-containing protein 4 (BRD4). Journal of Virology, 83(9):4127-39, 2009.

Lehoux, M., C.M. D’Abramo and J. Archambault. 2009. Molecular mechanisms of HPV-induced carcinogenesis. Public Health Genomics, 12(5-6):268-80, 2009. (Invited review, special issue on HPV pathogenesis and vaccine)

D’Abramo, C. M. and J. Archambault. Small Molecule Inhibitors of Human Papillomavirus Protein-Protein Interactions. Open Virol J., 5:80-95, 2011. (Invited review)

D’Abramo, C. M., A. Fradet-Turcotte, and J. Archambault. Human papillomavirus DNA replication: Insights into the structure and regulation of a eukaryotic DNA replisome. In "Small DNA Tumour Viruses", Ed. Kevin Gaston, Horizon Scientific Press. Book Chapter (in press), 2011.

Past CRS projects:

2006 Transcriptional regulation of human papillomavirus oncogenes by E2 and associated factors.

2004 Mechanisms of HPV E2-induced growth arrest and senescence of cervical cancer cell lines.