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Satya P. Kunapuli, PhDSatya P. Kunapuli, PhD

 

Professor, Physiology

Professor, Pharmacology

Director, Sol Sherry Thrombosis Research Center

Telephone:  215-707-4615

Fax:  215-707-4003

Office: Medical Research Building Room 217

Email: spk@temple.edu

 

Department of Physiology

Sol Sherry Thrombosis Research Center

Department of Pharmacology

 

Educational Background:

 

Andhra University, Kakinada, India
1972-1975, B.Sc., Chemistry

 

Andhra University, Waltair, India
1975-1977, M.Sc., Chemistry

 

Indian Institute of Science, Bangalore, India
1984, Ph.D., Biochemistr
y

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Research Interests:

 

The focus of research in my laboratory is on the molecular pharmacology and physiology of nucleotide receptors in cardiovascular system. We have active interest in the molecular mechanisms of ADP induced platelet activation. We have demonstrated three nucleotide receptors on platelets and cloned the P2Y1 receptor, coupled to activation of phospholipase C from a platelet library. We have demonstrated that the P2Y1 receptor plays an essential role in the ADP-induced platelet shape change and aggregation. Our long term goals in this project include delineation of signal transduction pathways from the three nucleotide receptors, identification of ligand binding sites on the P2Y1 receptor, cloning of the P2Y12 receptor coupled to inhibition of adenylyl cyclase, and characterization of the desensitization mechanisms of the P2Y receptors in platelets. Our lab interests in this field include the signaling events downstream of these receptors and the domains on these receptors coupling to corresponding G proteins and the ligands.

 

In the general field of platelet signaling, we are interested in the signaling events downstream of G12 and G13 proteins. We propose that signaling events downstream of G12/13 contribute to dense granule secretion, thromboxane generation, and Akt phosphorylation. We have identified interactions of G12/13 to HS-1 protein and shown that HS-1 null mice have increased bleeding times and abnormal platelet functions. Our future directions include identification of specific signaling molecules downstream of G12/13 that contribute to platelet function.

 

This work is supported by several research grants from National Institutes of Health.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

25077998. Liu L, Li J, Zhang Y, Zhang S, Ye J, Wen Z, Ding J, Kunapuli SP, Luo X, Ding Z, Salvianolic acid B inhibits platelets as a P2Y12 antagonist and PDE inhibitor: Evidence from clinic to laboratory. Thromb Res 134:4(866-76)2014 Oct

25047644. Newman TN, Liverani E, Ivanova E, Russo GL, Carpino N, Ganea D, Safadi F, Kunapuli SP, Tsygankov AY, Members of the novel UBASH3/STS/TULA family of cellular regulators suppress T-cell-driven inflammatory responses in vivo. Immunol Cell Biol :()2014 Jul 22

25029370. Teruel-Montoya R, Kong X, Abraham S, Ma L, Kunapuli SP, Holinstat M, Shaw CA, McKenzie SE, Edelstein LC, Bray PF, MicroRNA expression differences in human hematopoietic cell lineages enable regulated transgene expression. PLoS One 9:7(e102259)2014

24955517. Kostyak JC, Kunapuli SP, PKC? is dispensable for megakaryopoiesis. Platelets :(1-2)2014 Jun 23

24750049. Badolia R, Manne BK, Dangelmaier C, Kunapuli SP, IPA3 non-specifically enhances phosphorylation of several proteins in human platelets. Platelets :()2014 Apr 21

24433221. Bhavanasi D, Kostyak JC, Swindle J, Kilpatrick LE, Kunapuli SP, CGX1037 is a novel PKC isoform delta selective inhibitor in platelets. Platelets :()2014 Jan 16

24352480. Dangelmaier C, Manne BK, Liverani E, Jin J, Bray P, Kunapuli SP, PDK1 selectively phosphorylates Thr(308) on Akt and contributes to human platelet functional responses. Thromb Haemost 111:3(508-17)2014 Mar 3

24142066. Liverani E, Rico MC, Yaratha L, Tsygankov AY, Kilpatrick LE, Kunapuli SP, LPS-induced systemic inflammation is more severe in P2Y12 null mice. J Leukoc Biol 95:2(313-23)2014 Feb

24030758. Mao Y, Kunapuli SP, Trypsin causes platelet activation independently of known protease-activated receptors. Thromb Haemost 110:6(1241-9)2013 Dec

23861957. Garcia AE, Rico MC, Liverani E, DeLa Cadena RA, Bray PF, Kunapuli SP, Erosive arthritis and hepatic granuloma formation induced by peptidoglycan polysaccharide in rats is aggravated by prasugrel treatment. PLoS One 8:7(e69093)2013

23640884. Kim S, Cipolla L, Guidetti G, Okigaki M, Jin J, Torti M, Kunapuli SP, Distinct role of Pyk2 in mediating thromboxane generation downstream of both G12/13 and integrin aIIb▀3 in platelets. J Biol Chem 288:25(18194-203)2013 Jun 21

23571309. Getz TM, Manne BK, Buitrago L, Mao Y, Kunapuli SP, Dextran sulphate induces fibrinogen receptor activation through a novel Syk-independent PI-3 kinase-mediated tyrosine kinase pathway in platelets. Thromb Haemost 109:6(1131-40)2013 Jun

23341451. Manne BK, Getz TM, Hughes CE, Alshehri O, Dangelmaier C, Naik UP, Watson SP, Kunapuli SP, Fucoidan is a novel platelet agonist for the C-type lectin-like receptor 2 (CLEC-2). J Biol Chem 288:11(7717-26)2013 Mar 15

23104882. Zhang X, Szeto C, Gao E, Tang M, Jin J, Fu Q, Makarewich C, Ai X, Li Y, Tang A, Wang J, Gao H, Wang F, Ge XJ, Kunapuli SP, Zhou L, Zeng C, Xiang KY, Chen X, Cardiotoxic and cardioprotective features of chronic ▀-adrenergic signaling. Circ Res 112:3(498-509)2013 Feb 1

23097214. Liverani E, Rico MC, Garcia AE, Kilpatrick LE, Kunapuli SP, Prasugrel metabolites inhibit neutrophil functions. J Pharmacol Exp Ther 344:1(231-43)2013 Jan

22931288. Buitrago L, Tsygankov A, Sanjay A, Kunapuli SP, Cbl proteins in platelet activation. Platelets 24:6(419-27)2013

22362759. Bynagari-Settipalli YS, Lakhani P, Jin J, Bhavaraju K, Rico MC, Kim S, Woulfe D, Kunapuli SP, Protein kinase C isoform e negatively regulates ADP-induced calcium mobilization and thromboxane generation in platelets. Arterioscler Thromb Vasc Biol 32:5(1211-9)2012 May

22028806. Garcia AE, Mada SR, Rico MC, Dela Cadena RA, Kunapuli SP, Clopidogrel, a P2Y12 receptor antagonist, potentiates the inflammatory response in a rat model of peptidoglycan polysaccharide-induced arthritis. PLoS One 6:10(e26035)2011

21967979. Buitrago L, Langdon WY, Sanjay A, Kunapuli SP, Tyrosine phosphorylated c-Cbl regulates platelet functional responses mediated by outside-in signaling. Blood 118:20(5631-40)2011 Nov 17

21889790. Rico MC, Rough JJ, Manns JM, Del Carpio-Cano F, Safadi FF, Kunapuli SP, DeLa Cadena RA, Assembly of the prothrombinase complex on the surface of human foreskin fibroblasts: Implications for connective tissue growth factor. Thromb Res 129:6(801-6)2012 Jun

21736870. Bhavanasi D, Kim S, Goldfinger LE, Kunapuli SP, Protein kinase Cd mediates the activation of protein kinase D2 in platelets. Biochem Pharmacol 82:7(720-7)2011 Oct 1

21645497. Mayanglambam A, Bhavanasi D, Vijayan KV, Kunapuli SP, Differential dephosphorylation of the protein kinase C-zeta (PKC?) in an integrin aIIb▀3-dependent manner in platelets. Biochem Pharmacol 82:5(505-13)2011 Sep 1

21592972. Kim S, Kunapuli SP, Negative regulation of Gq-mediated pathways in platelets by G(12/13) pathways through Fyn kinase. J Biol Chem 286:27(24170-9)2011 Jul 8

21347357. Bhavaraju K, Lakhani PR, Dorsam RT, Jin J, Hitchcock IS, Sanjay A, Kunapuli SP, G(12/13) signaling pathways substitute for integrin aIIb▀3-signaling for thromboxane generation in platelets. PLoS One 6:2(e16586)2011 Feb 10

21261805. Nagy B Jr, Jin J, Ashby B, Reilly MP, Kunapuli SP, Contribution of the P2Y12 receptor-mediated pathway to platelet hyperreactivity in hypercholesterolemia. J Thromb Haemost 9:4(810-9)2011 Apr

21231822. Kim S, Kunapuli SP, P2Y12 receptor in platelet activation. Platelets 22:1(56-60)2011

21067313. Bhavaraju K, Georgakis A, Jin J, Gartner TK, Tomiyama Y, Nurden A, Nurden P, Kunapuli SP, Antagonism of P2Y12 reduces physiological thromboxane levels. Platelets 21:8(604-9)2010

20678065. Bynagari-Settipalli YS, Chari R, Kilpatrick L, Kunapuli SP, Protein kinase C - possible therapeutic target to treat cardiovascular diseases. Cardiovasc Hematol Disord Drug Targets 10:4(292-308)2010 Dec 1

20670370. Getz TM, Dangelmaier CA, Jin J, Daniel JL, Kunapuli SP, Differential phosphorylation of myosin light chain (Thr)18 and (Ser)19 and functional implications in platelets. J Thromb Haemost 8:10(2283-93)2010 Oct

20599922. Mao Y, Zhang L, Jin J, Ashby B, Kunapuli SP, Mutational analysis of residues important for ligand interaction with the human P2Y(12) receptor. Eur J Pharmacol 644:1-3(10-6)2010 Oct 10

20597033. Bhavaraju K, Mayanglambam A, Rao AK, Kunapuli SP, P2Y(12) antagonists as antiplatelet agents - Recent developments. Curr Opin Drug Discov Devel 13:4(497-506)2010 Jul

20585042. Thomas DH, Getz TM, Newman TN, Dangelmaier CA, Carpino N, Kunapuli SP, Tsygankov AY, Daniel JL, A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets. Blood 116:14(2570-8)2010 Oct 7

20441566. Garcia A, Kim S, Bhavaraju K, Schoenwaelder SM, Kunapuli SP, Role of phosphoinositide 3-kinase beta in platelet aggregation and thromboxane A2 generation mediated by Gi signalling pathways. Biochem J 429:2(369-77)2010 Jul 15

20400514. Daniel JL, Dangelmaier CA, Mada S, Buitrago L, Jin J, Langdon WY, Tsygankov AY, Kunapuli SP, Sanjay A, Cbl-b is a novel physiologic regulator of glycoprotein VI-dependent platelet activation. J Biol Chem 285:23(17282-91)2010 Jun 4

20158382. Mayanglambam A, Dangelmaier CA, Thomas D, Damodar Reddy C, Daniel JL, Kunapuli SP, Curcumin inhibits GPVI-mediated platelet activation by interfering with the kinase activity of Syk and the subsequent activation of PLCgamma2. Platelets 21:3(211-20)2010

20087365. Mao Y, Zhang M, Tuma RF, Kunapuli SP, Deficiency of PAR4 attenuates cerebral ischemia/reperfusion injury in mice. J Cereb Blood Flow Metab 30:5(1044-52)2010 May

19700402. Kim S, Mangin P, Dangelmaier C, Lillian R, Jackson SP, Daniel JL, Kunapuli SP, Role of phosphoinositide 3-kinase beta in glycoprotein VI-mediated Akt activation in platelets. J Biol Chem 284:49(33763-72)2009 Dec 4

19587372. Chari R, Kim S, Murugappan S, Sanjay A, Daniel JL, Kunapuli SP, Lyn, PKC-delta, SHIP-1 interactions regulate GPVI-mediated platelet-dense granule secretion. Blood 114:14(3056-63)2009 Oct 1

19485899. Rico MC, Rough JJ, Del Carpio-Cano FE, Kunapuli SP, DeLa Cadena RA, The axis of thrombospondin-1, transforming growth factor beta and connective tissue growth factor: an emerging therapeutic target in rheumatoid arthritis. Curr Vasc Pharmacol 8:3(338-43)2010 May

19437337. Mao Y, Jin J, Daniel JL, Kunapuli SP, Regulation of plasmin-induced protease-activated receptor 4 activation in platelets. Platelets 20:3(191-8)2009 May

19286657. Bynagari YS, Nagy B Jr, Tuluc F, Bhavaraju K, Kim S, Vijayan KV, Kunapuli SP, Mechanism of activation and functional role of protein kinase Ceta in human platelets. J Biol Chem 284:20(13413-21)2009 May 15

19213940. Chari R, Getz T, Nagy B Jr, Bhavaraju K, Mao Y, Bynagari YS, Murugappan S, Nakayama K, Kunapuli SP, Protein kinase C[delta] differentially regulates platelet functional responses. Arterioscler Thromb Vasc Biol 29:5(699-705)2009 May

19164598. Nagy B Jr, Bhavaraju K, Getz T, Bynagari YS, Kim S, Kunapuli SP, Impaired activation of platelets lacking protein kinase C-theta isoform. Blood 113:11(2557-67)2009 Mar 12

19073150. Jin J, Mao Y, Thomas D, Kim S, Daniel JL, Kunapuli SP, RhoA downstream of G(q) and G(12/13) pathways regulates protease-activated receptor-mediated dense granule release in platelets. Biochem Pharmacol 77:5(835-44)2009 Mar 1

19012179. Kahner BN, Dorsam RT, Kim S, Shankar H, Kitamura D, Kunapuli SP, Hematopoietic lineage cell-specific protein-1 (HS1) regulates PAR-mediated ERK activation and thromboxane generation in platelets. Platelets 19:8(614-23)2008 Dec

18674744. Rico MC, Manns JM, Driban JB, Uknis AB, Kunapuli SP, Dela Cadena RA, Thrombospondin-1 and transforming growth factor beta are pro-inflammatory molecules in rheumatoid arthritis. Transl Res 152:2(95-8)2008 Aug

18652571. Murugappan S, Chari R, Palli VM, Jin J, Kunapuli SP, Differential regulation of threonine and tyrosine phosphorylations on protein kinase Cdelta by G-protein-mediated pathways in platelets. Biochem J 417:1(113-20)2009 Jan 1

18404520. Tuluc F, Bredetean O, Brailoiu E, Meshki J, Garcia A, Dun NJ, Kunapuli SP, The priming effect of extracellular UTP on human neutrophils: Role of calcium released from thapsigargin-sensitive intracellular stores. Purinergic Signal 1:4(359-68)2005 Dec

18404491. Meshki J, Tuluc F, Bredetean O, Garcia A, Kunapuli SP, Signaling pathways downstream of P2 receptors in human neutrophils. Purinergic Signal 2:3(537-44)2006 Sep

18068154. Bhavaraju K, Kim S, Daniel JL, Kunapuli SP, Evaluation of [3-(1-methyl-1H-indol-3-yl-methylene)-2-oxo-2, 3-dihydro-1H-indole-5-sulfonamide] (OXSI-2), as a Syk-selective inhibitor in platelets. Eur J Pharmacol 580:3(285-90)2008 Feb 12

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trainees:

 

Postdoctoral Fellows:

Yingying Mao

Elisabetta Liverani

Beatrice Blanchard-Fillion

John Kostyak

Graduate Students:

Dheeraj Bhavanasi

Lorena Butriago

Bhanukanth Manne

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laboratory personnel:

 

Jianguo Jin, MD, Associate Scientist

T: 215-707-8339

Email: jjin@temple.edu


Carol Dangelmaier, Senior Laboratory Manager

T: 215-707-4334

Email: carol.dangelmaier@temple.edu

 

Monica Dupon, Research Technician

T: 215-707-8339

Email: monica.dupon@temple.edu

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