Interim Associate Dean for Academic Planning and Curriculum; Professor
Biology, Dean's Office for A & S
College of Arts and Sciencesalevesque@hartford.edu 860.768.5132 BC 160C
Education
PhD, Dartmouth College
BS, Providence College
Research Interests:
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.
(* Indicates undergraduate student author; + indicates graduate student author)
*Pappalardo, R. and Levesque, A. Analysis of p53 function in Neuroblastoma cell lines. The 11th Annual Undergraduate Research Symposium, William Paterson University, NJ, April 22, 2017. (resulted in first place award in the Cell and Molecular Biology division)
+Pawan, P., *Lipski, R., and Levesque, A.A. Oligomerization status of p53 serves as an indicator of sensitivity of p53 wildtype tumors to the therapeutic combination of DNA damaging agent and checkpoint inhibitor [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Research 2016;76(14 Suppl):Abstract nr 3693.
*Lipski, R., and Levesque, A.A. Analysis of p53 oligomerization and sensitivity to checkpoint inhibitors in neuroblastoma. In: Proceedings of the 104rd Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, D.C. Philadelphia (PA): AACR; 2013. Abstract nr 2220.
*Lipski, R., *Lippincott, D.J., *Durden, B.C., *Kaplan, A.R., *Keiser, H.E., *Park, J.H., and Levesque, A.A. p53 dimers associate with a head-to-tail response element to repress cyclin B transcription. PLoS One. 7: e42615, 2013.
*Lippincott, D.J., *Lipski, R., *Durden, B.C., *Kaplan, A.R., *Keiser, H.E., *Park, J.H., and Levesque, A.A. p53 dimers associate with a head-to-tail element to repress cyclin B transcription. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; 2012. Abstract nr 2220.
*Lipski, R., and Levesque, A.A. Checkpoint analysis of neuroblastoma cell lines using SN38-induced arrest followed by checkpoint inhibitor UCN-01. Northeastern Sigma Xi Research Symposium, Queens College, CUNY, April 21, 2012.
Levesque, A.A. Using classroom response systems to facilitate the development of problem solving skills. CBE-Life Sci. Ed. 10:406-417, 2011.
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.
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.
Levesque, A.A., Kohn, E.A., Bresnick, E., and Eastman, A. Distinct roles for p53 transactivation and repression in preventing UCN-01-mediated abrogation of DNA damage-induced arrest at S and G2 cell cycle checkpoints. Oncogene. 24: 3786-3796, 2005.
Levesque, A.A., Kohn, E.A., Bresnick, E., and Eastman, A.: Distinct roles for p53 transactivation and repression in preventing UCN-01-mediated abrogation of DNA damage-induced arrest at S and G2 cell cycle checkpoints. In: Proceedings of the 96th Annual Meeting of the American Association for Cancer Research; 2005 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2005. Abstract nr 1047.
Levesque, A.A., Kohn, E.A., Bresnick, E., DiRenzo, J., and Eastman, A.: Loss of p53 activation and repression functions is required for UCN-01-mediated abrogation of DNA damage-induced cell cycle arrest. In: Proceedings of the 95th Annual Meeting of the American Association for Cancer Research; 2004 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2004. Abstract nr 184.