Perrotti, Danilo

Danilo Perrotti, Ph.D.

Assistant Professor
Primary Appointment
Department of Molecular Virology, Immunology and Medical Genetics Human Cancer Genetics Program

For More Information:
Please visit Human Cancer Genetics

Contact Information:
Lab Phone: (614)293-5944, Office Phone: (614) 293-5739,  Fax: (614) 293-5952
Address: 2001 Polaris Parkway, Lab: room 1310, office: room 205, Columbus, Ohio 43240

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:
Manzella L., Gualdi R., Perrotti D., Nicolaides N.C., Girlando G., Giuffrida M.A., Messina A. and B. Calabretta. The Interferon Regulatory Factors 1 and 2 bind to a segment of the human c-myb first    intron: possible role in the regulation of c-myb expression. Exp. Cell Res. 256(1):248-56., 2000

Venturelli D., Engelhard A., Perrotti D. and B. Calabretta. The nucleoside diphosphate kinase activity of DR-nm23 is not required for inhibition of differentiation and induction of apoptosis in 32Dcl3 myeloid precursor cells. Exp. Cell Res. 257(2):265-71, 2000.

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.  (#) corresponding author

Cirinna' M., R. Trotta, P. Salomoni, P. Kossev, M. Wasik, D. Perrotti and B. Calabretta.. Bcl-2 Expression Restores the Leukemogenic Potential of a BCR/ABL Mutant Defective in Transformation.  Blood 96(12):3915-21, 2000.

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/EBP* expression through the translation inhibitory activity of the hnRNP E2. Nature Genetics 30: 48-58, 2002 (#) corresponding author

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 and B. Calabretta. Post-transcriptional mechanisms in BCR/ABL leukemogenesis: Role of the shuttling RNA binding proteins. Oncogene 21:8577-83, 2002

Truong B-T. H., Lee Y-J, Lodie T.A., Park D. J., Perrotti D., Watanabe N., Koeffler H. P., Nakajima H., Tenen D.G. and Kogan S.C. (2002) CCAAT/Enhancer Binding Proteins Repress the Leukemic Phenotype of Acute Myeloid Leukemia. Blood 101:1141-1148. 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.  (*) Corresponding Author.

Marcucci G., D. Perrotti and Caligiuri M.A. Understanding the molecular basis of Imatinib Mesylate therapy in CML and the related mechanisms of resistance. Clin. Cancer Res. 9:1248-252, 2003.                                                                            

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

Perrotti D.*, R. Trotta and B. Calabretta. Altered Translation: Possible mechanism for CML disease progression.   Cell Cycle 2: 177-180, 2003 (*) Corresponding Author.                                                                                    

Perrotti D*, Marcucci G. and Caligiuri MA. Loss of C/EBP* and Favorable Prognosis of Acute Myeloid Leukemia: A biological paradox. Journal of Clinical Oncology 22(4), 2004. (*)Corresponding Author.

Perrotti D* and Calabretta B. Translational Regulation by the p210 BCR/ABL Oncoprotein. Oncogene 23(18):3222-9, 2004 (*): Corresponding Author.          

Calabretta B and Perrotti D. The Biology of CML Blast Crisis. Blood 103(11):4010-22, 2004.

Liu S, Shen T, Rush LJ, Klisovic MI, Ford JL, Yu J, Becknell B, Li Y, Liu C, Vukosavljevic T, Whitman SP, Chang K-S, Byrd JC, Perrotti D, Plass C and G. Marucci.  RUNX1/MTG8 Associates With DNA Methyltransferase 1 to Disrupt Gene Expression In Acute Myeloid Leukemia.  Cancer Res Feb 15;65(4):1277-84, 2005

Perrotti D.*, Turturro F. and Neviani P. BCR/ABL, mRNA Translation and Apoptosis. Cell Death Differ  6:534-40, 2005.  (*)Corresponding Author.

Marcucci G. Baldus C.D., Ruppert A.S., Radmacher M.D., Mrózek K., Whitman S.P., Klisovic M.I., Kolitz J.E., Edwards C.G., Vardiman J.W., Powell B.L., Baer M.R., Moore J.O., Perrotti D., Caligiuri M.A., Carroll A.J., Larson R.A., de la Chapelle A. and Bloomfield C.D. Overexpression of the ETS Transcription Factor ERG Predicts a Worse Outcome in Acute Myeloid Leukemia with Normal Karyotype: A Cancer and Leukemia Group B Study. Journal of Clinical Oncology 2005 in press. 

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., Caligiuri M.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.

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.

Perrotti D. and Neviani P. ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia. Br. J. Cancer, 95:775-81, 2006.

Perrotti D. and Neviani P. From mRNA metabolism to Cancer therapy: CML shows the way. Clin. Cancer Res. 13(6):1638-42, 2007.

Chang JS., Santhanam R., 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/EBP?-driven Myeloid Differentiation. . Blood. 2007 May 2; [Epub ahead of print]

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.  September  2007.