Alfonso Bellacosa, MD, PhD
Adjunct Associate Professor, Department of Biochemistry, Drexel University College of Medicine
Adjunct Professor, College of Science and Technology, Temple University
Adjunct Professor, Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University
- 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
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
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.
Grier, J.T., Forbes, L.R., Monaco-Shawver, L., Oshinsky, J., Atkinson, T.P., Moody, C., Pandey, R., Campbell, K.S., and Orange, J.S. (2012) Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity. J. Clin. Invest., 122:3769-3780. PMCID: 3461929. - See more at: http://www.fccc.edu/research/pid/campbell/index.html#sthash.6kcGJyaq.dpu..., M., Radinsky, O., Cohen, L., Yossef, R., Shemesh, A., Braiman, A., Mandelboim, O., Campbell, K.S. and Porgador, A. (2015) Regulation of natural cytotoxicity receptors through interactions with heparin sulfate proteoglycans in -cis: a lesson from NKp44. Eur. J. Immunol., 45:1180-1191. PMCID: PMC4415513.
Purdy, A.K., Alvarez-Arias, D.A., Oshinsky, J., James, A.M., Serebriiskii, I., and Campbell, K.S. (2014) The AP-2 clathrin adaptor mediates endocytosis of an inhibitory killer cell Ig-like receptor (KIR) in human NK cells. J. Immunol., 193:4675-4683. PMCID: 4269369.
MacFarlane 4th, A.W., Jillab, M., Plimack, E.R., Hudes, G.R., Uzzo, R.G., Litwin, S., Dulaimi, E., Al-Saleem, T., and Campbell, K.S. (2014) PD-1 expression on peripheral blood cells increases with stage in renal cell carcinoma patients and is rapidly reduced after surgical tumor resection. Cancer Immunol. Res., 2:320-331. PMCID: 4007343.
Mentlik James, A., Cohen, A.D., and Campbell, K.S. (2013) Combination therapies to enhance anti-tumor responses by NK cells. Front. Immunol., 4:481, PMCID: 3870292.
Brusilovsky, M., Cordoba, M., Rosental, B., Hershkovitz, O., Andrake, M.D., Pecherskaya, A., Einarson, M.B., Zhou, Y., Braiman, A., Campbell, K.S., and Porgador, A. (2013) Genome-wide siRNA screen reveals a new cellular partner of NK cell receptor KIR2DL4: heparan sulfate directly modulates KIR2DL4-mediated responses. J. Immunol., 191:5256-5267. PMCID: 3836631.
Campbell, K.S., and Hasegawa, J. (2013) NK cell biology: an update and future directions. J. Allergy Clin. Immunol., 132:536-544, PMCID: 3775709.
Grier, J.T., Forbes, L.R., Monaco-Shawver, L., Oshinsky, J., Atkinson, T.P., Moody, C., Pandey, R., Campbell, K.S., and Orange, J.S. (2012) Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity. J. Clin. Invest., 122:3769-3780. PMCID: 3461929.
Campbell, K.S., and Purdy, A.K. (2011) Structure/Function of Human Killer Cell Ig-like Receptors: Lessons from Polymorphisms, Evolution, Crystal Structures, and Mutations. Immunology, 132:315-325, PMCID: 3044898.
Miah, S.M.S., Purdy, A.K., Rodin, N.B., MacFarlane 4th, A.W., Oshinsky, J., Alvarez-Arias, D.A., and Campbell, K.S. (2011) Ubiquitylation of an internalized killer cell Ig-like receptor by Triad3A disrupts sustained NF-kappaB signaling. J. Immunol.
Purdy, A.K. and Campbell, K.S. (2009) SHP-2 expression negatively regulates NK cell function. J. Immunol. 183:7234-7243. PMCID: 2783243.
MacFarlane 4th, A.W., Yamazaki, T., Fang, M., Sigal, L.J., Kurosaki, T., and Campbell, K.S. (2008) Enhanced NK cell development and function in BCAP-deficient mice. Blood 112:131-140. PMCID: 2435684.
Miah, S.M.S., Hughes, T.L., and Campbell, K.S. (2008) KIR2DL4 differentially signals downstream functions in human NK cells through distinct structural modules. J. Immunol. 180: 2922-2932.
Alvarez-Arias, D.A., and Campbell, K.S. (2007) Protein kinase C regulates expression and function of inhibitory killer cell Ig-like receptors in NK cells. J. Immunol. 179: 5281–5290.
Kikuchi-Maki, A., Catina, T.L., and Campbell, K.S. (2005) Cutting Edge: KIR2DL4 transduces signals into human NK cells through association with Fc receptor gamma protein. J. Immunol., 174:3859-3863.