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

2010 - present

  • 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.
  • Bruno T, Desantis A, Bossi G, Di Agostino S, Sorino C, De Nicola F, Iezzi S, Franchitto A, Benassi B, Galanti S, La Rosa F, Floridi A, Bellacosa A, Passananti C, Blandino G, Fanciulli M. Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation. Cancer Cell. 2010 Aug 9;18(2):122-34.
  • 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.

2000 - 2009

  • Catalucci D, Latronico MV, Ceci M, Rusconi F, Young HS, Gallo P, Santonastasi M, Bellacosa A, Brown JH, Condorelli G. At Increases Sarcoplasmic Reticulum Ca2+ Cycling by Direct Phosphorylation of Phospholamban at Thr(17). J Biol Chem. 2009 Oct;284(41):28180-7.
  • 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.
  • 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.
  • Fu J, Fong K, Bellacosa A, Ross E, Apostolou S, Bassi DE, Jin F, Zhang J, Cairns P, de C, Braunewell KH, Klein-Szanto AJ. VILIP-1 Downregulation in Non-Small Cell Lung Carcinomas: Mechanisms and Prediction of Survival. PLoS ONE. 2008;3(2):e1698.
  • Caretti E, Devarajan K, Coudry R, Ross E, Clapper ML, Cooper HS, Bellacosa A. Comparison of RNA amplification methods and chip platforms for microarray analysis of samples processed by laser capture microdissection. J Cell Biochem. 2008 Feb;103(2):556-63.
  • Sundermeyer M, Bellacosa A, Meropol N. Molecular Targeting of Colorectal Cancer. In: Antman K, Wadler S, editors. Molecular Targeting in Oncology . Totowa, NJ: Humana Press; 2008. p. 133-63.
  • Yeung AT, Patel BB, Li XM, Seeholzer SH, Coudry RA, Cooper HS, Bellacosa A, Boman BM, Zhang T, Litwin S, Ross EA, Conrad P, Crowell JA, Kopelovich L, Knudson A. One-hit effects in cancer: altered proteome of morphologically normal colon crypts in familial adenomatous polyposis. Cancer Res. 2008 Sep 15;68(18):7579-86.
  • Caretti E, Devarajan K, Coudry R, Ross E, Clapper ML, Cooper HS, Bellacosa A. Comparison of RNA amplification methods and chip platforms for microarray analysis of samples processed by laser capture microdissection. J Cell Biochem. 2008 Feb 1;103(2):556-63.
  • Howard JH, Frolov A, Tzeng CD, Stewart A, Shlykova S, Heslin MJ, Bellacosa A, Arnoletti JP. Epigenetic downregulation of the DNA repair gene MED1/MBD4 in colorectal and ovarian cancer. Cancer Biol Ther. 2007 Jan;8(1):94-100.
  • Julien S, Puig I, Caretti E, Bonaventure J, Nelles L, van Roy F, Dargemont C, Garcia de Herreros A, Bellacosa A, Larue L. Activation of NF-kappa B by Akt upregulates Snail expression and induces epithelium mesenchyme transition. Oncogene. 2007 Nov;26 (53):7445-56.
  • Patel BB, Li XM, Dixon MP, Blagoi EL, Seeholzer SH, Chen Y, Miller CG, He YA, Tetruashvily M, Chaudhry AH, Ke E, Xie J, Cooper H, Bellacosa A, Clapper ML, Boman BM, Zhang T, Litwin S, Ross EA, Conrad P, Crowell JA, Kopelovich L, Knudson A, Yeung AT. Searchable high-resolution 2D gel proteome of the human colon crypt. J Proteome Res. 2007 Jun;6(6):2232-8.
  • Pimkin M, Caretti E, Canutescu A, Yeung JB, Cohn H, Chen Y, Oleykowski C, Bellacosa A, Yeung AT. Recombinant nucleases CEL I from celery and SP I from spinach for mutation detection. BMC Biotechnol. 2007 Jun;7:29.
  • 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 Aug 1;66(15):7686-93.
  • Yeung A, Patel B, Li XM, Paterson M, Blagoi E, Seeholzer S, Chen Y, He A, Chaudhry A, Ke E, Coundry R, Cooper H, Bellacosa A, Clapper M, Boman B, Zhang T, Ross E, Litwin S, Conrad P, Crowell J, Kopelovich L, Knudson A. Heterozygous Adenomatous Polyposis Coli mutation in human colon crypt alters the proteome. Mol Cell Proteomics. 2006 Oct;5(10):213.
  • Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3 ' kinase/AKT pathways. Oncogene. 2005 Nov;24(50):7443-54.
  • Amoletti JP, Upson J, Babb JS, Bellacosa A, Watson JC. Differential stromal and epithelial localization of cyclooxygenase-2 (COX-2) during colorectal tumorigenesis. J Exp Clin Cancer Res. 2005 Jun;24(2):279-87.
  • Bellacosa A, Kumar CC, Di Cristofano A, Testa JR. Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res. 2005;94:29-86.
  • Cortellino S, Turner DP, Albino D, Bellacosa A. Induction of deoxyribonucleic acid damage by alkylating agents. Methods Mol Biol. 2004;285:121-5.
  • Stoyanova R, Clapper ML, Bellacosa A, Henske EP, Testa JR, Ross EA, Yeung AT, Nicolas E, Tsichlis N, Li YS, Linehan WM, Howard S, Campbell KS, Godwin AK, Boman BM, Crowell JA, Kopelovich L, Knudson AG. Altered gene expression in phenotypically normal renal cells from carriers of tumor suppressor gene mutations. Cancer Biol Ther. 2004 Dec;3(12):1313-21.
  • Stoyanova R, Upson JJ, Patriotis C, Ross EA, Henske EP, Datta K, Boman B, Clapper ML, Knudson AG, Bellacosa A. Use of RNA amplification in the optimal characterization of global gene expression using cDNA microarrays. J Cell Physiol. 2004 Dec;201(3):359-65.
  • Turner DP, Yeung AT, Bellacosa A. Ultraviolet irradiation of cells. Methods Mol Biol. 2004;285:133-7.
  • Upson JJ, Stoyanova R, Cooper HS, Patriotis C, Ross EA, Boman B, Clapper ML, Knudson AG, Bellacosa A. Optimized procedures for microarray analysis of histological specimens processed by laser capture microdissection. J Cell Physiol. 2004 Dec;201(3):366-73.
  • Bellacosa A, Testa JR, Moore R, Larue L. A portrait of AKT kinases: human cancer and animal models depict a family with strong individualities. Cancer Biol Ther. 2004 Mar;3(3):268-75.
  • Cortellino S, Turner D, Masciullo V, Schepis F, Albino D, Daniel R, Skalka AM, Meropol NJ, Alberti C, Larue L, Bellacosa A. The base excision repair enzyme MED1 mediates DNA damage response to antitumor drugs and is associated with mismatch repair system integrity. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15071-6.
  • Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, van Roy F, Lee-Kwon W, Donowitz M, Tsichlis PN, Larue L. The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 2003 May;63(9):2172-8.
  • Neri LM, Borgatti P, Tazzari PL, Bortul R, Cappellini A, Tabellini G, Bellacosa A, Capitani S, Martelli AM. The phosphoinositide 3-kinase/AKT1 pathway involvement in drug and all-trans-retinoic acid resistance of leukemia cells. Molecular Cancer Research. 2003 Jan;1(3):234-46.
  • Bellacosa A. Genetic hits and mutation rate in colorectal tumorigenesis: versatility of Knudson's theory and implications for cancer prevention. Genes Chromosomes Cancer. 2003 Dec;38(4):382-8.
  • Bellacosa A, Moss EG. RNA repair: damage control. Curr Biol. 2003 Jun 17;13(12):R482-4.
  • Borgatti P, Martelli AM, Tabellini G, Bellacosa A, Capitani S, Neri LM. Threonine 308 phosphorylated form of Akt translocates to the nucleus of PC12 cells under nerve growth factor stimulation and associates with the nuclear matrix protein nucleolin. J Cell Physiol. 2003 Jul;196(1):79-88.
  • Condorelli G, Drusco A, Stassi G, Bellacosa A, Roncarati R, Iaccarino G, Russo MA, Gu YS, Dalton N, Chung C, Latronico MV, Napoli C, Sadoshima J, Croce CM, Ross J. Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice. 2002;:1125.
  • Viglietto G, Motti ML, Bruni P, Melillo RM, D'Alessio A, Califano D, Vinci F, Chiappetta G, Tsichlis P, Bellacosa A, Fusco A, Santoro M. Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. Nat Med. 2002 Oct;8(10):1136-44.
  • Arnoletti JP, Midzah A, Upson J, Majmundar A, Godwin A, Bellacosa A. Hypermethylation of the MED1 DNA repair gene promoter in ovarian cancer. Ann Surg Oncol. 2002 Jan;9(1):12.
  • Drummond JT, Bellacosa A. Human DNA mismatch repair in vitro operates independently of methylation status at CpG sites. Nucleic Acids Res. 2001 Jun;29(11):2234-43.
  • Testa JR, Bellacosa A. AKT plays a central role in tumorigenesis. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):10983-5.
  • Testa JR, Bellacosa A. Commentary - AKT plays a central role in tumorigenesis. Proc Natl Acad Sci U S A. 2001 Sep;98(20):10983-5.
  • Xiao GH, Jeffers M, Bellacosa A, Mitsuuchi Y, Vande Woude GF, Testa JR. Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):247-52.
  • Bellacosa A. Role of MED1 (MBD4) Gene in DNA repair and human cancer. J Cell Physiol. 2001 May;187(2):137-44.
  • Bellacosa A. Functional interactions and signaling properties of mammalian DNA mismatch repair proteins. Cell Death Differ. 2001 Nov;8(11):1076-92.
  • De Vita G, Berlingieri MT, Visconti R, Castellone MD, Viglietto G, Baldassarre G, Zannini M, Bellacosa A, Tsichlis PN, Fusco A, Santoro M. Akt/protein kinase B promotes survival and hormone-independent proliferation of thyroid cells in the absence of dedifferentiating and transforming effects. Cancer Res. 2000 Jul;60(14):3916-20.
  • De Vita G, Melillo RM, Carlomagno F, Visconti R, Castellone MD, Bellacosa A, Billaud M, Fusco A, Tsichlis PN, Santoro M. Tyrosine 1062 of RET-MEN2A mediates activation of Akt (protein kinase B) and mitogen-activated protein kinase pathways leading to PC12 cell survival. Cancer Res. 2000 Jul;60(14):3727-31.
  • Petronzelli F, Riccio A, Markham GD, Seeholzer SH, Genuardi M, Karbowski M, Yeung AT, Matsumoto Y, Bellacosa A. Investigation of the substrate spectrum of the human mismatch-specific DNA N-glycosylase MED1 (MBD4): fundamental role of the catalytic domain. J Cell Physiol. 2000 Dec;185(3):473-80.
  • Petronzelli F, Riccio A, Markham GD, Seeholzer SH, Stoerker J, Genuardi M, Yeung AT, Matsumoto Y, Bellacosa A. Biphasic kinetics of the human DNA repair protein MED1 (MBD4), a mismatch-specific DNA N-glycosylase. J Biol Chem. 2000 Oct 20;275(42):32422-9.
  • Bellacosa A, Petronzelli F, Riccio A, Markham GD, Seeholzer SH, Stoerker J, Genuardi M, Yeung AT, Matsumoto Y. Biochemical characterization of the mismatch repair protein MED1 (MBD4). Am J Hum Genet. 2000 Oct;67(4):492.
  • Borgatti P, Martelli AM, Bellacosa A, Casto R, Massari L, Capitani S, Neri LM. Translocation of Akt/PKB to the nucleus of osteoblast-like MC3T3-E1 cells exposed to proliferative growth factors. FEBS Lett. 2000 Jul;477(1-2):27-32.
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1990 - 1999

  • Riccio A, Aaltonen LA, Godwin AK, Loukola A, Percesepe A, Salovaara R, Masciullo V, Genuardi M, Paravatou-Petsotas M, Bassi DE, Ruggeri BA, Klein-Szanto AJ, Testa JR, Neri G, Bellacosa A. The DNA repair gene MBD4 (MED1) is mutated in human carcinomas with microsatellite instability. Nat Genet. 1999 Nov;23(3):266-8.
  • Bellacosa A, Cicchillitti L, Schepis F, Riccio A, Yeung AT, Matsumoto Y, Golemis EA, Genuardi M, Neri G. MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3969-74.
  • Eves EM, Xiong W, Bellacosa A, Kennedy SG, Tsichlis PN, Rosner MR, Hay N. Akt, a target of phosphatidylinositol 3-kinase, inhibits apoptosis in a differentiating neuronal cell line. Mol Cell Biol. 1998 Apr;18(4):2143-52.
  • Muise-Helmericks RC, Grimes HL, Bellacosa A, Malstrom SE, Tsichlis PN, Rosen N. Cyclin D expression is controlled post-transcriptionally via a phosphatidylinositol 3-kinase Akt-dependent pathway. J Biol Chem. 1998 Nov;273(45):29864-72.
  • Aoki M, Batista O, Bellacosa A, Tsichlis P, Vogt PK. The Akt kinase: Molecular determinants of oncogenicity. Proc Natl Acad Sci U S A. 1998 Dec;95(25):14950-5.
  • Bellacosa A, Chan TO, Ahmed NN, Datta K, Malstrom S, Stokoe D, McCormick F, Feng J, Tsichlis P. Akt activation by growth factors is a multiple-step process: the role of the PH domain. Oncogene. 1998 Jul 23;17(3):313-25.
  • Cattani P, Hohaus S, Bellacosa A, Genuardi M, Cavallo S, Rovella V, Almadori G, Cadoni G, Galli J, Maurizi M, Fadda G, Neri G. Association between cyclin D1 (CCND1) gene amplification and human papillomavirus infection in human laryngeal squamous cell carcinoma. Clin Cancer Res. 1998 Nov;4(11):2585-9.
  • Ahmed NN, Grimes HL, Bellacosa A, Chan TO, Tsichlis PN. Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase. Proc Natl Acad Sci U S A. 1997 Apr;94(8):3627-32.
  • Chang HW, Aoki M, Fruman D, Auger KR, Bellacosa A, Tsichlis PN, Cantley LC, Roberts TM, Vogt PK. Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase. Science. 1997 Jun;276(5320):1848-50.
  • Kennedy SG, Wagner AJ, Conzen SD, Jordan J, Bellacosa A, Tsichlis PN, Hay N. The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev. 1997 Mar;11(6):701-13.
  • Nieborowska-Skorska M, Bellacosa A, Martinez R, Majewski M, Choi JK, Trotta R, Wlodarski P, Perrotti D, Chan TO, Wasik MA, Tsichlis PN, Calabretta B, Skorski T. Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt-dependent pathway. Blood. 1997 Nov;90(10):795.
  • Petrukhin L, Dangel J, Vanderveer L, Costalas J, Bellacosa A, Grana G, Daly M, Godwin AK. The I1307K APC mutation does not predispose to colorectal cancer in Jewish Ashkenazi breast and breast-ovarian cancer kindreds. Cancer Res. 1997 Dec 15;57(24):5480-4.
  • Skorski T, Bellacosa A, NieborowskaSkorska M, Majewski M, Martinez R, Choi JK, Trotta R, Wlodarski P, Perrotti D, Chan TO, Wasik MA, Tsichlis PN, Calabretta B. Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt-dependent pathway. EMBO J. 1997 Oct;16(20):6151-61.
  • Testa JR, Bellacosa A. Membrane translocation and activation of the Akt kinase in growth factor-stimulated hematopoietic cells. Leuk Res. 1997 Nov-Dec;21(11-12):1027-31.
  • Datta K, Bellacosa A, Chan TO, Tsichlis PN. Akt is a direct target of the phosphatidylinositol 3-kinase. Activation by growth factors, v-src and v-Ha-ras, in Sf9 and mammalian cells. J Biol Chem. 1996 Nov 29;271(48):30835-9.
  • Hohaus S, Cavallo S, Bellacosa A, Genuardi M, Galli J, Cadoni G, Almadori G, Lauriola L, Litwin S, Maurizi M, Neri G. Telomerase activity in human laryngeal squamous cell carcinomas. Clin Cancer Res. 1996 Nov;2(11):1895-900.
  • Lissy NA, Bellacosa A, Sonoda G, Miller PD, Jhanwar SC, Testa JR. Isolation, characterization, and mapping to human chromosome 11q24-25 of a cDNA encoding a highly conserved putative transmembrane protein, TMC. Biochim Biophys Acta. 1996 May 2;1306(2-3):137-41.
  • Bellacosa A, Defeo D, Godwin AK, Bell DW, Cheng JQ, Altomare DA, Wan MH, Dubeau L, Scambia G, Masciullo V, Ferrandina G, Panici PB, Mancuso S, Neri G, Testa JR. Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int J Cancer. 1995 Aug;64(4):280-5.
  • Bellacosa A, Datta K, Bear SE, Patriotis C, Lazo PA, Copeland NG, Jenkins NA, Tsichlis PN. Effects of provirus integration in the Tpl-1/Ets-1 locus in Moloney murine leukemia virus-induced rat T-cell lymphomas: levels of expression, polyadenylation, transcriptional initiation, and differential splicing of the Ets-1 mRNA. J Virol. 1994 Apr;68(4):2320-30.
  • Taguchi T, Bellacosa A, Zhou JY, Gilbert DJ, Lazo PA, Copeland NG, Jenkins NA, Tsichlis PN, Testa JR. Chromosomal localization of the Ox-44 (CD53) leukocyte antigen gene in man and rodents. Cytogenet Cell Genet. 1993;64(3-4):217-21.
  • Ahmed NN, Franke TF, Bellacosa A, Datta K, Gonzalez-Portal ME, Taguchi T, Testa JR, Tsichlis PN. The proteins encoded by c-akt and v-akt differ in post-translational modification, subcellular localization and oncogenic potential. Oncogene. 1993 Jul;8(7):1957-63.
  • Bellacosa A, Franke TF, Gonzalezportal ME, Datta K, Taguchi T, Gardner J, Cheng JQ, Testa JR, Tsichlis PN. Structure, expression and chromosomal mapping of C-AKT - relationship to V-AKT and its implications. Oncogene. 1993 Mar;8(3):745-54.
  • Cheng JQ, Godwin AK, Bellacosa A, Taguchi T, Franke TF, Hamilton TC, Tsichlis PN, Testa JR. AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9267-71.
  • Taguchi T, Bellacosa A, Zhou J, Lazo PA, Tsichlis PN, Testa JR. Mapping of the OX44 human-leukocyte antigen gene to 1p12-p13 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1991;58(3-4):1863.
  • Bellacosa A, Lazo PA, Bear SE, Tsichlis PN. The rat leukocyte antigen MRC OX-44 is a member of a new family of cell surface proteins which appear to be involved in growth regulation. Mol Cell Biol. 1991 May;11(5):2864-72.
  • Bellacosa A, Testa JR, Staal SP, Tsichlis PN. A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region. Science. 1991 Oct 11;254(5029):274-7.
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1980 - 1989

  • Bear SE, Bellacosa A, Lazo PA, Jenkins NA, Copeland NG, Hanson C, Levan G, Tsichlis PN. Provirus insertion in Tpl-1, an Ets-1-related oncogene, is associated with tumor progression in Moloney murine leukemia virus-induced rat thymic lymphomas. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7495-9.
  • Bellacosa A, Lazo PA, Bear SE, Shinton S, Tsichlis PN. Induction of multiple independent T-cell lymphomas in rats inoculated with MOloney murine leukemia virus. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4269-72.
  • Bellacosa A, Bear SE, Shinton S, Tsichlis PN. Moloney leukemia-virus induced multicentric lymphomas. Clin Res. 1988 Apr;36(3):A494-A494.
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