Perrotti, Danilo

Associate Professor

Department of Molecular Virology, Immunology and Medical Genetics Human Cancer Genetics Program

Contact Information:

Office:

892 Biomedical Research Tower
460 W 12th Avenue
Columbus, OH 43210
Ph. (614) 293-5739
email: danilo.perrotti@osumc.edu

Research Interest:

Chronic Myelogenous Leukemia - oncogenic tyrosine kinases, signal transduction pathways and RNA binding proteins

Research summary:

Dr. Perrotti's research is aimed at assessing the molecular mechanisms leading to leukemic transformation of hematopoietic cells. Specific areas of interest are: a) Role of RNA binding proteins in blastic transformation of Chronic Myelogenous Leukemia; b) Signal transduction in Leukemia; c) Mechanisms regulating expression and activity of oncogenic kinases.

Selected Publications:

Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, Lovat F, Fadda P, Mao C, Nuovo GJ, Zanesi N, Crawford M, Ozer GH, Wernicke D, Alder H, Caligiuri MA, Nana-Sinkam P, Perrotti D, Croce CM. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2110-6. Epub 2012 Jul 2.

Blum W, Schwind S, Tarighat SS, Geyer S, Eisfeld AK, Whitman S, Walker A, Klisovic R, Byrd JC, Santhanam R, Wang H, Curfman JP, Devine SM, Jacob S, Garr C, Kefauver C, Perrotti D, Chan KK, Bloomfield CD, Caligiuri MA, Grever MR, Garzon R, Marcucci G. Clinical and pharmacodynamic activity of bortezomib and decitabine in acute myeloid leukemia. Blood. 2012 Jun 21;119(25):6025-31. Epub 2012 May 7.

Ranganathan P, Heaphy CE, Costinean S, Stauffer N, Na C, Hamadani M, Santhanam R, Mao C, Taylor PA, Sandhu S, He G, Shana'ah A, Nuovo GJ, Lagana A, Cascione L, Obad S, Broom O, Kauppinen S, Byrd JC, Caligiuri M, Perrotti D, Hadley GA, Marcucci G, Devine SM, Blazar BR, Croce CM, Garzon R. Regulation of acute graft-versus-host disease by microRNA-155. Blood. 2012 May 17;119(20):4786-97. Epub 2012 Mar 9.

Salas A, Ponnusamy S, Senkal CE, Meyers-Needham M, Selvam SP, Saddoughi SA, Apohan E, Sentelle RD, Smith C, Gault CR, Obeid LM, El-Shewy HM, Oaks J, Santhanam R, Marcucci G, Baran Y, Mahajan S, Fernandes D, Stuart R, Perrotti D, Ogretmen B. Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A. Blood. 2011 Jun 2;117(22):5941-52. Epub 2011 Apr 28.

Veronese A, Visone R, Consiglio J, Acunzo M, Lupini L, Kim T, Ferracin M, Lovat F, Miotto E, Balatti V, D'Abundo L, Gramantieri L, Bolondi L, Pekarsky Y, Perrotti D, Negrini M, Croce CM. Mutated beta-catenin evades a microRNA-dependent regulatory loop. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4840-5. Epub 2011 Mar 7.

Perrotti D, Harb JG. BCR-ABL1 kinase-dependent alteration of mRNA metabolism: potential alternatives for therapeutic intervention. Leuk Lymphoma. 2011 Feb;52 Suppl 1:30-44. Epub 2011 Jan 11. Review.Eiring AM., Neviani P. Garton C., Spizzo R., Liu S., Oaks JJ., Hickey C., Santhanam R., Harb JG., Chandler JC., Andino R., Cortes J., Hokland P., Huettner CS, Bhatia R., Roy DC., Caligiuri MA, Marcucci G., Garzon R., Croce CM, Calin GA., and Perrotti D. A non-canonical decoy binding activity of miR-328 controls hnRNP-E2 translation inhibitory function in leukemic blasts. Cell 140(5):652-65, 2010.

Samanta AK, Chakraborty SN, Wang Y, Kantarjian H, Sun X, Hood J, Perrotti D and Arlinghaus RB. Jak2 inhibition deactivates Lyn kinase through the SET-PP2A-SHP1 pathway causing apoptosis in drug-resistant cells from chronic myelogenous leukemia patients. Oncogene28(14):1669-81, 2009.

Trotta R, Col JD, Yu J, Ciarlariello D, Thomas B, Zhang X, Allard J 2nd, Wei M, Mao H, Byrd JC, Perrotti D, Caligiuri MA. TGF-beta utilizes SMAD3 to inhibit CD16-mediated IFN-gamma production and antibody-dependent cellular cytotoxicity in human NK cells. J. Immunol.181(6):3784-92, 2008.

Eiring A., Oaks J., Neviani P., Chang JS., Notari M., Santhanam R., Willis W., Roy DC., Volinia S., Marcucci G., Caligiuri MA., Leone GW and Perrotti D*. Identification of Novel Posttranscriptional Targets of BCR/ABL Oncoprotein by Ribonomics: Role of E2F3 in BCR/ABL leukemogenesis. Blood. 2008;111(2):816-28.

Thomas EK., Cancelas JA., Chae H-D., Cox AD., Keller PJ., Perrotti D., Neviani P., Druker BJ, Setchell KDR, Zheng Y., Harris EC. and D.A Williams. Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease. Cancer Cell, 12(5):467-78, 2007.

Trotta R., Dal Col J, Allard J., Neviani P., Santhanam R., Mao H., Becknell B, Yu J, Modi A., Blaser BW, Perrotti D*. and Caligiuri MA*. The PP2A Inhibitor SET Regulates Natural Killer Cells IFN-{gamma} Production. J. Exp. Med. 204(10):2397-405, 2007. (*: equal senior contribution)

Neviani P., Santhanam R., Oaks J., Eiring A., Notari M., Blaser BW., Liu S., Trotta R., Muthusamy N., Verrills, N., Gambacorti-Passerini C., Druker BJ., Cortes J., Marcucci G., Chen CS, Roy DC., Caligiuri MA., Bloomfield CD., Byrd J and D. Perrotti*. FTY720, a new and alternative strategy for treating blast crisis CML and Ph1 ALL. J Clin. Invest., 117(9):2408-2421, 2007.

Liu Q., Zhao X., Frissora F, Ma Y., Santhanam R., Jarjoura D., Lehman A., Perrotti D, Chen C-S, Dalton JT, Muthusamy N. and Byrd JC. FTY720 Mediates Cytotoxicity in Chronic Lymphocytic Leukemia and Lymphoblastic Leukemia/Lymphoma by a PP2A dependent mechanism. Blood Aug. 2007

Galietta A., Gunby R., Stano P., Carniti C., Bach A.i, Tartar C., Tucker P., Huang C., Colombo E., Pulford K., Puttini M., Piazza R., Ruchatz H., Perrotti D., and Gambacorti-Passerini C. NPM/ALK Binds and Phosphorylates the RNA/DNA Binding Protein PSF in Anaplastic Large Cell Lymphoma. Blood  110(7): 2600-9, 2007.

Chang JS., SanthanamR., Trotta R., Neviani P., Eiring A., Briercheck E., Ronchetti M., Roy DC., Calabretta B., Caligiuri MA and D. Perrotti.  High levels of the BCR/ABL oncoprotein are required for the MAPK-hnRNP E2-dependent suppression of C/EBPa-driven Myeloid Differentiation. . Blood. 110(3):994-1003, 2007

C. Guerzoni, M. Bardini, S. Mariani, G. Ferrari-Amorotti, M.L. Panno,P. Neviani, Y. Zhang, R. Martinez, D. Perrotti, and B. Calabretta.Inducible activation of C/EBPb, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BCR/ABL-expressing cells. Blood.;107:4080-9, 2006.

Notari M., Neviani P., Santhanam R., Galietta A, Chang JS., Blaser B.W., Willis A.E., Roy D.C., Caligiuri M.A., Marcucci G. and D. Perrotti*. A MAPK/hnRNP K pathway controls BCR/ABL oncogenic potential by regulating c-myc mRNA translation. Blood,107:2507-16, 2006.

Neviani P., Santhanam R., Trotta R., Notari M., Blaser B.W., Liu S., Mao H, Chang JS, Galietta A, Uttam A, Roy D.C., Valtieri M., Bruner-Klisovic R., CaligiuriM.A., Bloomfield C.D., Marcucci G., and D. Perrotti*. The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein. Cancer Cell.;8:355-68, 2005.

Keeshan K., G. Santilli, F. Corradini, D. Perrotti* and B. Calabretta. The transcriptional activation function of C/EBPa ?is required for induction of granulocytic differentiation. Blood, 103:1267-75, 2003.

Trotta, R., T. Vignudelli, O. Candini, R. V. Intine, L. Pecorari, C. Guerzoni, G. Santilli, M.W. Byrom, S. Goldoni, L.P. Ford, M. A. Caligiuri, R.J. Maraia, D. Perrotti*, and B. Calabretta. BCR/ABL activates mdm2 mRNA translation via the La antigen. Cancer Cell,3:145-60.2003

Iervolino A., G. Santilli, R. Trotta, C. Guerzoni, V. Cesi, A. Bergamaschi, C. Gambacorti-Passerini, B. Calabretta, and D. Perrotti. hnRNP A1 nucleocytoplasmic shuttling activity is required for normal myelopoiesis and BCR/ABL leukemogenesis. Mol. Cell. Biol. 22:2255-66, 2002.

Perrotti D#, Cesi V, Trotta R., Guerzoni C, Santilli G., Campbell K., Iervolino A., Condorelli F., Gambacorti-Passerini C, Caligiuri MA. and B. Calabretta. BCR/ABL suppresses C/EBPa expression through the translation inhibitory activity of the hnRNP E2. Nature Genetics,30: 48-58, 2002.

Perrotti D#., Iervolino A., Cesi V., Cirinna’ M., Lombardini S., Grassilli E., Bonatti S., Claudio P.P and B. Calabretta. BCR/ABL prevents c-Jun-mediated and proteasome-dependent TLS/FUS proteolysis through a PKCbII-dependent pathway. Mol. Cell. Biol,20(16): 6159-69,2000.

D. Perrotti#, Bonatti S., Trotta R., Martinez R., Skorski T., Salomoni P., Grassilli E., Iozzo R.V., Cooper D.R. and B. Calabretta. 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.

Bellon T#, D. Perrotti# and B. Calabretta. Granulocytic differentiation of normal hematopoietic precursor cells induced by the transcription factor PU.1 correlates with negative regulation of the c-myb promoter. Blood,.90(5):1828-1839,1997. (#): Equal contribution