Bio Chem Building 160C
PhD Dartmouth College | BS Providence College
The hereditary material of every cell is DNA, which encodes the information directing all of the normal processes of the cell. When that information is changed, or mutated, the normal functions of the cell are altered. Such mutations are a hallmark of cancer, in which defects in the normal cell division regulatory mechanisms are disrupted. The link between DNA mutations and cancer is highlighted by the fact that many inherited cancer predisposition syndromes are due to mutations in key genes that are normally involved in protecting cells from cell growth and division in the face of DNA damage.
DNA damage can occur spontaneously, or it can be induced by exposure to several different classes of carcinogens, such as UV light, various chemicals, or cigarette smoke. Therefore, DNA damage is a constant threat to the integrity of our hereditary material. To guard against this threat, our cells employ cell cycle checkpoints, which inhibit cell division to allow time for repair of the DNA damage. If the cells successfully repair the DNA damage, they recover and proceed with cell division. If the DNA damage is irreparable, the cells activate cell death pathways. In either case, the cell is prevented from dividing with damaged DNA, thus eliminating the possibility that any defects in DNA will become permanent mutations that may lead to cancer. The p53 tumor suppressor protein plays a major role in both the cell cycle arrest and cell death in response to DNA damage. The significance of its role in these processes is evident in the fact that p53 is defective in greater than 50% of all human tumors. The primary goal of my research is to increase our understanding of the mechanisms by which p53 protects cells from DNA damage.
Recent Grants, Publications, and Meeting Presentations:
Recipient of the Young Investigator’s Grant from the Breast Cancer Alliance, 2009-2010. Project title: “Mechanism of regulation of cyclin B expression by p53 in breast epithelial cells”
*Tamiso, E., and Levesque, A.A.: Tetramerization of p53 is not required for p53-dependent repression of Cyclin B expression. In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-178. (*Undergraduate author)
Levesque, A.A., Fanous, A.A., Poh, A., and Eastman, A. Defective p53 signaling in p53 wildtype tumors attenuates p21waf1 induction and cyclin B repression rendering them sensitive to Chk1 inhibitors that abrogate DNA damage-induced S and G2 arrest. Mol. Canc. Ther. 7: 252-262, 2008.
Levesque, A.A. and Eastman, A. p53-based Cancer Therapies: Is p53 the Achilles Heel of the Tumor? Carcinogenesis. 28: 13-20, 2006.