Research Programs:Tumor Biology and Progression
Associate Professor and Section Leader, University of Minnesota's Hormel Institute, Signal Transduction and Apoptosis Section

pruvolo@hi.umn.edu
507-437-9645 —office
507-437-9646 — lab
Preferred method of contact: e-mail

Dr. Ruvolo received his B.S. in Biochemistry from Columbia University in New York in 1983. He obtained his Ph.D. in Molecular Biology from Albert Einstein College of Medicine in Bronx, New York in 1989. He conducted postdoctoral training under the mentorship of Dr. Allan D. Hess in the Department of Oncology at Johns Hopkins University where he studied the molecular mechanisms regulating T cell autoimmunity in diseases such as graft-versus-host disease. Dr. Ruvolo joined Dr. W. Stratford May's group in 1996 as a research instructor at University of Texas Medical Branch in Galveston, Texas and then as a research assistant professor at the University of Florida. With the May group, he studied the signal transduction pathways that regulate the anti-apoptotic molecule, BCL2. In 2002, Dr. Ruvolo joined the Institute of Molecular Medicine at the University of Texas Health Science Center in Houston, Texas as an assistant professor. There he studied the stress signaling pathways mediated by the sphingolipid ceramide. He joined the University of Minnesota's Hormel Institute in Austin, Minnesota in 2007 as an associate professor and as section leader of the Signal Transduction and Apoptosis Section. His current research focuses on the role of ceramide-activated enzymes such as Protein Phosphatase 2A (PP2A), c-JUN N-Terminal Kinase (JNK), and dsRNA Dependent Protein Kinase (PKR) in chemoresistance in leukemia and lung cancer. Dr. Ruvolo was on the editorial board of Leukemia from 2001 until 2006. He is a member of the American Hematology Society and a member of the American Association for Cancer Research.

Research Interests

The Ruvolo laboratory studies the signaling mechanisms that regulate cell death and ultimately influence tumor development and drug resistance in cancers such as leukemia and lung cancer. A major focus of the laboratory is to characterize signal transduction pathways that are regulated by the sphingolipid ceramide. Ceramide is a potent second signal molecule and its production is a near universal feature of programmed cell death (also known as apoptosis). One major project involves the regulation of the BCL2 oncogene by phosphorylation, particularly those pathways involving ceramide activated protein phosphatase 2A (PP2A). Suppression of the PP2A isoform responsible for BCL2 dephosphorylation promotes chemoresistance to drugs such as etoposide and adriamycin in acute lymphoblastic leukemia cells. The Ruvolo laboratory is currently investigating how the PP2A isoform that acts as the BCL2 phosphatase is regulated. Another project involves the role of c-JUN N-Terminal Kinase (JNK) in apoptosis in lung cancer. Inhibition of JNK protects lung cancer cells from ceramide-mediated apoptosis. The Ruvolo laboratory is currently investigating which JNK substrates are required for ceramide-induced cell death and if this mechanism is important in apoptosis induced by anti-cancer drugs used in lung cancer.

Selected Publications

Ruvolo P, Carr BK, May WS. A functional role for protein kinase Ca in Bcl2 phosphorylation and suppression of apoptosis. J Biol Chem. 1998;273:25436-25442.

Ruvolo PP, Deng X, Ito T, Carr BK, May WS. Ceramide-induced apoptosis requires mitochondrial PP2A-mediated Bcl2 phosphorylation. J Biol Chem. 1999;274:20296-20300.

Ruvolo PP, Gao F, Blalock WL, Deng X, May WS. Ceramide regulates protein synthesis by a novel mechanism involving the cellular PKR activator RAX. J Biol Chem. 2001;276:11754-11768.

Ruvolo PP. Ceramide regulates cellular homeostasis via diverse stress signaling pathways. Leukemia 2001;15:1153-1160.

Ruvolo PP, Clark W, Mumby M, Gao F, May WS. A functional role for the B56 alpha subunit of protein phosphatase 2A in ceramide-mediated regulation of Bcl2 phosphorylation status and function. J Biol Chem. 2002;277:22847-22852.

Andreeff M, Ruvolo PP. PKC alpha-mediated chemoresistance in acute lymphoblastic leukemia derived REH cells requires Bcl2. Leukemia 2004;18: 505-512.

Kurinna SM, Tsao CC, Nica AF, Jiffar T, Ruvolo PP. Ceramide promotes apoptosis in lung cancer derived A549 cells by a mechanism involving JNK. Cancer Res. 2004;64:7852-7856.

Konopleva M, Contractor R, Kurinna SM, Chen W, Andreeff M, Ruvolo PP. The novel triterpenoid CDDO-Me promotes apoptosis in acute myeloid leukemia cells by suppression of MAPK pathways and the activation of p38. Leukemia 2005;19:1350-1354.

Kurinna SM, Konopleva M, Palla S, Chen W, Kornblau S, Contractor R, Deng X, May WS, Andreeff M, Ruvolo PP. Bcl2 phosphorylation and active PKC alpha are associated with poor survival in AML. Leukemia 2006;20:1316-131.

Alonso-Escolano D, Medina C, Cieslik K, Radomski A, Jurasz P, Santos-Martinez MJ, Jiffar T, Ruvolo P, Radomski M. PKC delta mediates platelet-induced breast cancer cell invasion. J Pharmacol Exp Ther. 2006;318:373-380.

Konopleva M, Contractor R, Tsao T, Samudio I,Ruvolo PP, Kitada S, Deng X, Zhai D, Yuexi S, Sneed T, Verhaegen M, Soengas M, Ruvolo VR, McQueen T, Schober WD, Watt JC, Jiffar T, Ling X, Marini F, Harris D, Dietrich M, Estrov Z, McCubrey J, May WS, Reed JC, Andreeff M. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 2006;10:375-388.

Tabe Y, Jin L, Contractor R, Gold D, Ruvolo P, Radke S, Xu Y, Tsutusmi-Ishii Y, Miyake K, Miyake N, Kondo S, Ohsaka A, Nagaoka I, Andreeff M, Konopleva M. Novel role of HDAC inhibitors in AML1/ETO AML cells: activation of apoptosis and phagocytosis through induction of annexin A1. Cell Death Differ. 2007;14:1443-1456.

Seminara AR, Ruvolo PP, Murad F. LPS/IFNgamma-induced RAW 264.7 apoptosis is regulated by both nitric oxide-dependent and -independent pathways involving JNK and the Bcl-2 family. Cell Cycle 2007;6:1772- 1778.

Tsao CC, Nica AF, Kurinna SM, Jiffar T, Mumby M, Ruvolo PP. Mitochondrial protein phosphatase 2A regulates cell death induced by simulated ischemia in kidney NRK-52E cells. Cell Cycle 2007;6:2377-23785.

Kong G, Wang D, Wang H, Wu J, Bielawski J, Konopleva M, Andreeff M, Ruvolo PP, Maurer BJ. Synthetic triterpenoids have cytotoxicity in pediatric acute lymphoblastic leukemia cell lines but cytotoxicity is independent of induced ceramide increase in MOLT-4 cells. Leukemia 2008, in press.