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Thomas Jefferson University - Bruno Calabretta, MD, PhD
Bruno Calabretta, MD, PhD

Cancer Biology
Thomas Jefferson University
Jefferson Medical College
Department of Cancer Biology
Professor

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Mailing Address
233 South 10th St-life Sci Bld
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: (215) 503-4522
Bruno.Calabretta@mail.tju.edu
Qualifications
M.D., University of Modena, 1977

Ph.D., University of Roma, 1987
Expertise and Research Interests
The process of normal hematopoiesis requires the sequential coordination of many complex events. These include the interaction of stimulatory growth factors with their membrane receptors, generation of the appropriate signal followed by its transduction through the cell membrane and cytoplasm into the nucleus, and finally, DNA synthesis and cell division. Accordingly, it seems reasonable to assume that perturbations in any of these controlled events are likely to result in altered cell growth patterns and possibly in the emergence of cells with a leukemic phenotype, especially in the presence of cumulative alterations in these various components of the proliferative program. As a paradigm of this concept, our studies center on the investigation of the role of the oncogenic BCR/ABL protein in transformation of hematopoietic stem cells and in the role of transcription factors with hematopoietic-specific functions (c-Myb and C/EBPalpha) in normal hematopoiesis and in leukemogenesis.In particular, the studies in the BCR/ABL area will focus on the mechanisms involved in suppression of apoptosis and autophagy. The studies on c-Myb and C/EBPalpha will focus on the effects of these two transcription factors on regulation of normal and leukemic stem cells.
Keywords
Biological Signal Transduction; Cancer; Cancer Biology; Cancer Prevention; Carcinogenesis; Cell Differentiation; Cell Growth Regulation; Cellular Oncology; Colony Stimulating Factor; Gene Expression; Genetic Promoter Element; Hematopoiesis; Human Tissue; Leukemia; Molecular Cloning; Molecular Oncology; Oncogene; Transcription Factor; Transfection
Publications
  • Salomoni P, Calabretta B. Targeted therapies and autophagy: New insights from chronic myeloid leukemia. Autophagy. 14;5(7), 2009.
  • Pecorari L, Marin O, Silvestri C, Candini O, Rossi E, Guerzoni C, Cattelani S, Mariani SA, Corradini F, Ferrari-Amorotti G, Cortesi L, Bussolari R, Raschellà G, Federico MR, Calabretta B. Elongation Factor 1 alpha interacts with phospho-Akt in breast cancer cells and regulates their proliferation, survival and motility. Mol Cancer. 3;8:58, 2009.
  • Vitali R, Mancini C, Cesi V, Tanno B, Piscitelli M, Mancuso M, Sesti F, Pasquali E, Calabretta B, Dominici C, Raschellà G. Activity of tyrosine kinase inhibitor Dasatinib in neuroblastoma cells in vitro and in orthotopic mouse model. Int J Cancer. 125(11):2547-2555, 2009.
  • Bellodi, C., Lidonnici, M.R., Hamilton, A., Helgason, V., Soliera, A.R., Ronchetti, M., Galavotti, S., Young, K., Selmi, T., Van Etten, R., Dnato, N., Hunter, A., Dinsdale, D., Tirro, E., Vigneri, P., Nicotera, P., Dyer, M., Holyaoke, T., Salomoni, P., Calabretta, B. Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia positive cells including primary CML stem cells. J. Clin. Invest. 119(5):1109-23, 2009.
  • Soliera, A., Lidonnici, M., Ferrari-Amorotti, G., Prisco, M. Zhang, Y., Martinez, R., Donato, N., Calabretta, B. Transcriptional repression of c-Myb and GATA-2 is involved in the biological effects of C/EBPa in p210 BCR/ABL expressing cells (c-Myb and GATA-2 in BCR/ABL leukemogenesis). Blood, 112:1942-1950, 2008.
  • Vitali, R., Mancini, C., Cesi, V., Tanno, B., Mancuso, M., Bossi, G., Zhang, Y., Martinez, R.V., Calabretta, B., Dominici, C., Raschellà, G. Slug (SNAI2) Down-Regulation by RNA Interference Facilitates Apoptosis and Inhibits Invasive Growth in Neuroblastoma Preclinical Models. Clin. Cancer Res. 14(14):4622-30, 2008.
  • Cattelani, S., Defferrari, R., Marsilio, S., Bussolari, R., Candini, O., Corradini, F., Ferrari-Amarotti, G., Guerzoni, C., Pecorari, L., Menin, C., Bertorelle, R., Altavista, P., McDowell, H., Boldrini, R., Dominici, C., Tonini, G., Raschella, G., Calabretta, B. Impact of single nucleotide polymorphism (SNP309) in the MDM2 gene on neuroblastoma development and aggressiveness: results of a pilot study on 239 patients. Clin. Cancer Res., 14(11):3248-53, 2008.
  • Lidonnici, M.R., Corradini, F., Waldron, T., Bender, T.P., Calabretta, B. Requirement of c-Myb for p210BCR/ABL dependent transformation of myeloid progenitors and leukomogenesis. Blood 111:4771-4778, 2008.
  • Schwab, R., Bussolari, R., Corvetta, D., Chayka, O., Santilli, G., Kwok, J.M., Amorotti, G.F., Tonini, G.P., Iacoviello, L., Bertorelle, R., Memin, G., Hubank, M., Calabretta, B., Sala, B. Isolation and functional assessment of common, polymorphic variants of the B-MYBproto-oncogene associated with a reduced cancer risk. Oncogene 27:2924-1933, 2008.
  • Iotti, G., Ferrari-Amorotti, G., Rosafio, C., Corradini, F., Lidonnici, M.R., Ronchetti, M., Bardini, M., Zhang, Y., Martinez, R., Blasi, F. and Calabretta, B. Expression of CCL9/MIP-1g is repressed by BCR/ABL and its restoration suppresses in vivo leukemogenesis of 32D-BCR/ABL cells. Oncogene 26:3482-3491, 2007.
  • Chang, J.S., Sauthanam, R., Trotta, R., Ering, A., Biercheck, E., Roy, D.C., Ronchetti, M., Calabretta, B., Caligiuri, M.A. and Perrotti, D. Suppression of C/EBPa-driven myeloid differentiation in blast crisis CML progenitors requires increased BCR/ABL expression and depends on the integrity of the MAPKERK1/2-hnRNPE2 inhibitory pathway. Blood 100:994-1003, 2007.
  • Bussolari, R., Candini, O., Colomer, D., Corradini, F., Guerzoni, C., Mariani, S., Catellani, S., Silvestri, C., Pecorari, L., Iacobucci, I., Soverini, S., Fasano, T., Martinelli, G., Cervantes, F. and Calabretta, B. Coding sequence and intron-exon junctions of the c-myb gene are intact in the chronic phase and blast crisis stages of chronic myeloid leukemia patients. Leukemia Res. 31:163-167, 2007.
  • Guerzoni, C., Ferrari-Amorotti, G., Bardini, M., Mariani, S. and Calabretta, B. Effects of C/EBPa and C/EBPb in BCR/ABL expressing cells: differences and similarities. Cell Cycle, 5: 1254-1257, 2006.
  • Ferrari-Amorotti, G., Keeshan, K., Zattoni, M., Guerzoni, C., Iotti, G., Cattelani, S., Donato, N.J. and Calabretta, B. Leukemogenesis induced by wild type and STI571-resistant BCR/ABL is potently suppressed by C/EBPa. Blood,108: 1353-1362, 2006.
  • Guerzoni, C., Bardini, M., Mariani, S.A., Ferrari-Amorotti, G., Neviani, P., Panno, M.L., Zhang, Y., Martinez, R., Perrotti, D. and Calabretta, B. Inducible activation of C/EBPb, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BCR/ABL-expressing cells. Blood, 107(10):4080-9, 2006.
  • Corradini, F., Cesi, V., Bartella, V., Pani, E., Bussolari, R., Candini, O., Calabretta, B. Enhanced proliferative potential of hematopoietic cells expressing degradation-resistant c-Myb mutants. J. Biol. Chem. 280(34):30254-30262, 2005
  • Cesi, V., Giuffrida, M.L., Vitali, R., Tanno, B., Mancini, C., Calabretta, B. and Raschellà, G. C/EBPa and b mimic retinoic acid activation of IGFBP-5 in neuroblastoma cells by a mechanism independent from binding to their site. Exp. Cell. Res., 305: 179-189, 2005.
  • Tanno, B., Cesi, V., Vitali, R., Sesti, F., Giuffrida, M.L., Mancini, C., Calabretta, B. and Raschellà, G. Silencing of endogenous IGFBP-5 by micro RNA interference affects proliferation, apoptosis and differentiation of neuroblastoma cells. Cell Death and Diff., 12: 213-223, 2005.
  • Prisco, M., Maiorana, A., Guerzoni, C., Calin, G., Calabretta, B., Voit, R., Grummt, I. and Baserga, R. Role of prescadillo and upstream binding factor in the proliferation and differentiation of murine myeloid cells. Mol. Cell. Biol., 24:5421-5433, 2004.
  • Calabretta, B. and Perrotti, D. The biology of the CML blast crisis. Blood, 103:4010-4022, 2004.
  • Perrotti, D. and Calabretta, B. Translational regulation by the p210 BCR/ABL oncoprotein. Oncogene, 23:3222-3229, 2004.
  • Keeshan, K., Santilli, G., Corradini, F., Perrotti, D. and Calabretta, B. The transcription activation function of C/EBPa is required for induction of granulocytic differentiation. Blood, 102:1267-1275, 2003.
  • Trotta, R., Vignudelli, T., Candini, O., Intine, R.V., Pecorari, L., Guerzoni, C., Santilli, G., Byrom, M.W., Goldoni, S., Ford, L.P., Caligiuri, M.A., Maraia, R.J., Perrotti, D. and Calabretta, B. BCR/ABL activates mdm2 mRNA transalation via the La antigen. Cancer Cell, 3:145-160, 2003.
  • Kim, B.-C., Mamura, M., Choi, K.-S., Calabretta, B. and Kim, S.-J. TGFb1-induced apoptosis in FaO hepatoma cells. Mol. Cell. Biol., 22:1368-1378, 2002.
  • Cesi, V., Tanno, B., Vitali, R., Mancini, C., Calabretta, B. and Raschellá, G. Cyclin D1-dependent regulation of B-myb activity in early stages of neuroblastoma differentiation. Cell Death and Diff., 9:1232-1239, 2002.
  • Rosen, K., Shi, W. Calabretta, B. and Filmus, J. Cell detachment triggers p38 MAP Kinase-dependent overexpression of FAS ligand: a novel mechanism of anoikis in intestinal epithelial cells. J. Biol. Chem., 277:46123-46130, 2002.
  • Perrotti, D. and Calabretta, B. Post-transcriptional mechanisms in BCR/ABL leukemogenesis: role of shuttling RNA-binding proteins. Oncogene, 21:8577-8583, 2002.
  • Perrotti, D., Cesi, V., Trotta, R., Guerzoni, C., Santilli, G., Campbell, K., Iervolino, A., Condorelli, F., Gambacorti-Passerini, C., Caligiuri, M.A. and Calabreta, B. BCR-ABL suppresses C/EBP a expression through inhibitory action of hnRNP E2. Nature Genet, Vol. 30, 48-58, 2002.
  • Iervolino, A., Santilli, G., Trotta, R., Guerzoni, C., Cesi, A.B., Gambacorti-Passerini, C., Calabretta, B. and Perrotti, D. hnRNP A1 Nucleocytoplasmic Shuttling Activity is Required for Normal Myelopoiesis and BCR/ABL Leukemogenesis. Mol. Cell Biol., 22:2255-2266, 2002.
  • Tanno, B., Negroni, A., Vitali, R., Pirozzoli, M.C., Cesi, V., Mancini, C., Calabretta, B. and Raschellá, G. Expression of IGFBP-5 in neublastoma cells is regulated at the transcriptional level by c-Myb and B-Myb via direct and indirect mechanisms. J. Biol. Chem., 277:23172-23180, 2002.
  • Condorelli, F., Salomoni, P., Cottoret, S., Srinivasula, S., Alnermi, E., and Calabretta, B.Caspase cleavage enhances the apoptosis-inducing effects of BAD. Mol. Cell. Biol., 21:3025-3036, 2001.
  • Powzaniuk, M., Trotta, R., Loza, M.J., Harth, A., Iozzo, R.V., Eisenlohr, L.C., Perussia, B., and Calabretta, B. B-Myb overexpression results in activation and increased Fas/FasL-mediated cytotoxicity of T and NK cells. J. Immunol., 167:242-249, 2001.
  • Salomoni, P., Conderelli, F., Sweeney, S.M., and Calabretta, B. Versatility of BCR/ABL-expressing leukemic cells in circumventing pro-apoptotic BAD effects. Blood, 96:676-684, 2000.
  • Perrotti, D., Iervolino, A., Cesi, V., Cirinna, M., Grassilli, E., Bonatti, S., Claudio, P.P. and Calabretta, B. BCR/ABL prevents c-Jun-mediated, proteasome-dependent and ubiquitin-independent TLS/FUS proteolysis through a PKCbll-dependent pathway. Mol. Cell. Biol., 20:6159-6169, 2000.
  • Sevignani, C., Cranston, A., Iozzo, R.V., Fishel, R., and Calabretta, B. Spontaneous and mutagen-induced transformation of primary cultures of Msh2-/- p53-/- colonocytes. Cancer Res., 59:5882-5886, 1999.
  • Perrotti, D., Bonatti, S.., Trotta, R., Martinez, R., Skorski, T., Salomoni, P., Grassilli, E., Iozzo, R.V., Cooper, D.R. and Calabretta, B.: TLS/FUS, a pro-oncogene involved in multiple chromosomal translocations, is a novel regulator of BCR/ABL-mediated leukemogenesis. EMBO J., 17(15):4442-4455, 1998.

Individual Expertise profile of Bruno Calabretta, MD, PhD, Copyright © Bruno Calabretta, MD, PhD.
Last Updated by Bruno Calabretta, MD, PhD : Wednesday, September 30, 2009 10:45:02 AM



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