Alfonso Bellacosa, MD, PhD

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Professor

Adjunct Professor, Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University

Adjunct Professor, College of Science and Technology, Temple University

Adjunct Associate Professor, Department of Biochemistry, Drexel University College of Medicine

Research Program

Cancer Signaling and Epigenetics

Lab Overview

The goal of our research is to clarify how alterations in genomic and epigenomic stability of CpG sequences lead to altered development and cancer formation. Mutations are often the consequence of defective DNA repair; we are particularly interested in the mammalian DNA repair enzymes that protect the integrity of CpG sequences in DNA: MBD4 and TDG. 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 discovered a role of TDG in active DNA demethylation (Cortellino et al. Cell, 2011), which is highly relevant in the context of the recently identified oxidized cytosine variants that have expanded the information content of the genome: TDG is the only enzyme that efficiently removes 5-formylcytosine and 5-carboxylcytosine produced by the TET dioxygenases.

We are also interested in innovative approaches of cancer prevention and therapy that are rationally based on the analysis of genetic and epigenetic alterations of cancer cells.

Finally, we are interested in the molecular basis of hereditary cancer syndromes.

Thymine DNA Glycosylase in Active DNA Demethylization
Demythalization pathways
Mutagenesis by deamination of 5-methylcytosine and cytosine at CpG sites
Lack of cilia in Ift122 knock-out embryos
Ingenuity Pathway Analysis

Educational Background

PhD, Genetics, University of Paris, 2001-2004
Postgraduate School of Hematology, Catholic University Medical School, Rome, 1988-1992
MD, Catholic University Medical School, Rome, 1982-1988
University of Naples Second Medical School, 1981-1982

Honors & Awards

PhD, avec la mention Très Honorable, 2004
"Sir Paul Girolami" Award for Innovative Research in Biology and Medicine, presented by Nobel Laureates Edmund Fischer and Rita Levi-Montalcini, 1993
Fellowship from the Italian Association for Cancer Research, 1992-1994
Postdoctoral Fellowship from the "Lawrence Greenwald Foundation for Research on Leukemia and Lymphoma," 1989-1991
MD, 110/110 Summa Cum Laude, 1988

People

Rossella Tricarico, PhD

Research Associate

P3023

215-728-4013

Rossella.Tricarico@fccc.edu
Gabrielle Scher, BA

Student Intern

P3023

215-728-4013

Gabrielle.Scher@fccc.edu
Carly Scher, BA (exp. 2017)

Student Intern

P3023

215-728-4013

Carly.Scher@fccc.edu

Research Interests

Role of DNA Repair in the stability of the genome and epigenome
Regulation of DNA methylation and DNA demethylation in development and cancer
Targeted epigenetic therapy
Hereditary Cancer

Selected Publications

Mancuso P., Tricarico R., Bhattacharjee V., Cosentino L., Kadariya Y., Jelinek J., Nicolas E., Einarson M., Beeharry N., Devarajan K., Katz R.A., Dorjsuren D.G., Sun H., Simeonov A., Giordano A., Testa J.R., Davidson G., Davidson I., Larue L., Sobol R.W., Yen T.J., Bellacosa A., Thymine DNA glycosylase as a novel target for melanoma. Oncogene. 38(19): 3710-3728, 2019.PMC6563616 https://www.ncbi.nlm.nih.gov/pubmed/30674989.

Sannai M., Doneddu V., Giri V., Seeholzer S., Nicolas E., Yip S.C., Bassi M.R., Mancuso P., Cortellino S., Cigliano A., Lurie R., Ding H., Chernoff J., Sobol R.W., Yen T.J., Bagella L., Bellacosa A. Modification of the base excision repair enzyme mbd4 by the small ubiquitin-like molecule sumo1. DNA Repair. 82: 102687, 2019.PMC6785017. https://www.ncbi.nlm.nih.gov/pubmed/31476572.

Turchetti D., Zuntini R., Tricarico R., Bellacosa A., Brca2 in ovarian development and function. N Engl J Med. 380(11): 1086-1087, 2019. https://www.ncbi.nlm.nih.gov/pubmed/30865813.

Xu J, Cortellino S, Tricarico R, Chang WC, Scher G, Devarajan K, Slifker M, Moore R, Bassi MR, Caretti E, Clapper M, Cooper H, Bellacosa A. Thymine DNA Glycosylase (TDG) is involved in the pathogenesis of intestinal tumors with reduced APC expression. Oncotarget, 8(52):89988-97, 2017. PMC5685726

Tricarico^,R., Cortellino, S., Riccio, A., Jagmohan-Changur^,S., van der Klift, H., Wijnen, J., Turner, D., Ventura, A., Rovella, V., Percesepe, A., Lucci-Cordisco, E., Radice, P., Bertario, L., Pedroni, M., Ponz de Leon, M., Mancuso, P., Devarajan, K., Cai, K.Q., Klein-Szanto, A.J.P., Neri, G., Møller, P., Viel, A., Genuardi, M., Fodde, R. and Bellacosa, A. Involvement of MBD4 inactivation in mismatch repair-deficient tumorigenesis. Oncotarget. 2015 Dec 15;6(40):42892-904. PubMed

Bellacosa, A. and Drohat A.C. Role of base excision repair in maintaining the genetic and epigenetic integrity of CpG sites. (Invited Review) DNA Repair, 32:33-42 (2015). PubMed

Bellacosa, A. Developmental disease and cancer: biological and clinical overlaps. (Invited Review) Am J Med Genet A, 161:2788-96 (2013). PubMed

Dalton, S.R. and Bellacosa, A. DNA Demethylation by TDG. Epigenomics 4: 459-467 (2012). PubMed

Cortellino, S., Xu, J., Sannai, M., Moore, R., Caretti, E., Cigliano, A., Le Coz, M., Devarajan, K., Wessels, A., Soprano, D., Abramowitz, L. K., Bartolomei, M.S. Rambow, F., Bassi, M.R., Bruno, T., Fanciulli, M., Renner, C., Klein-Szanto, A.J., 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 146:67-79 (2011). PubMed

Bellacosa, A., Godwin, A.K., Peri, S., Devarajan, K., Caretti, E., Vanderveer, L., Bove, B., Slater, C., Zhou, Y., Daly, M., Howard, S., Campbell, K., Nicolas, E., Yeung, A.T., Clapper, M.L., Crowell, J.A., Lynch, H.T., Ross, E., Kopelovich, L., Knudson, A.G. Altered gene expression in morphologically normal epithelial cells from heterozygous carriers of BRCA1 or BRCA2 mutations. Cancer Prev. Res. 3: 48–61 (2010). PubMed... Expand