Faculty Summaries
Alfonso Bellacosa, MD, PhD
Alfonso Bellacosa, MD, PhD
Professor
  • Adjunct Associate Professor, Department of Biochemistry, Drexel University College of Medicine
  • Adjunct Professor, College of Science and Technology, Temple University
  • Adjunct Associate Professor, Department of Microbiology and Immunology, Temple University School of Medicine
alfonso.bellacosa@fccc.edu
Office Phone: 215-728-4012
Lab Phone: 215-728-4013
Fax: 215-214-1590
Office: P3041
Lab: P3023
DNA Repair in Cancer and Development

Our research is focused on the analysis of genetic and epigenetic alterations of cancer cells in an effort to understand normal gene function and pathogenesis of disease, with the ultimate goal of identifying critical regulatory molecules/pathways as targets for innovative approaches of cancer prevention and therapy. Mutations in cancer cells are often the consequence of defective DNA repair that leads to a situation of "genomic instability." We are particularly interested in the mammalian DNA repair enzymes that protect the integrity of CpG sequences in DNA. This is important because mutations at CpG sites represent about one third of all point mutations in cancer. In addition, CpG sites are also important for regulation of gene activity by an epigenetic process called DNA methylation. We found that alterations in DNA repair can also cause altered DNA methylation patterns at the level of CpG sites resulting in a situation of "epigenomic instability" that is incompatible with normal development. Importantly, alterations of DNA methylation are also very frequent in cancer. Thus, the goal of this research is to clarify how alterations in genomic and epigenomic stability of CpG sequences lead to altered development and cancer formation.

Description of research projects
Selected Publications
  1. Cortellino S, Xu J, Sannai M, Moore R, Caretti E, Cigliano A, Le Coz M, Devarajan K, Wessels A, Soprano D, Abramowitz LK, Bartolomei MS, Rambow F, Bassi MR, Bruno T, Fanciulli M, Renner C, Klein-Szanto AJ, Matsumoto Y, Kobi D, Davidson I, Alberti C, Larue L, Bellacosa A. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell. 2011 146(1):67-79. PubMed
  2. Bellacosa A, Godwin AK, Peri S, Devarajan K, Caretti E, Vanderveer L, Bove B, Slater C, Zhou Y, Daly M, Howard S, Campbell KS, Nicolas E, Yeung AT, Clapper ML, Crowell JA, Lynch HT, Ross E, Kopelovich L, Knudson AG. Altered gene expression in morphologically normal epithelial cells from heterozygous carriers of BRCA1 or BRCA2 mutations. Cancer Prev Res. 2010 3(1):48-61. PubMed
  3. Howard JH, Frolov A, Tzeng CW, Stewart A, Midzak A, Majmundar A, Godwin AK, Heslin MJ, Bellacosa A, Arnoletti P. Epigenetic downregulation of the DNA repair gene MED1/MBD4 in colorectal and ovarian cancer. Cancer Biology & Therapy. 2009 Jan;8(1):94-100. PubMed
  4. Cortellino S, Wang C, Wang B, Bassi MR, Caretti E, Champeval D, Calmont A, Jarnik M, Burch J, Zaret KS, Larue L, Bellacosa A. Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4. Dev Biol. 2009 Jan 1;325(1):225-37. PubMed
  5. Julien S, Puig I, Caretti E, Bonaventure J, Nelles L, van Roy F, Dargemont C, de Herreros AG, Bellacosa A, Larue L. Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition. Oncogene. 2007 26(53):7445-56. PubMed
  6. Turner DP, Cortellino S, Schupp JE, Caretti E, Loh T, Kinsella TJ, Bellacosa A. The DNA N-glycosylase MED1 exhibits preference for halogenated pyrimidines and is involved in the cytotoxicity of 5-iododeoxyuridine. Cancer Res. 2006 66(15):7686-93. PubMed
All publications