Peipei Ping, Ph.D.
Professor of Physiology and Medicine

e-mail:
peipeiping@hotmail.com peipeiping@earthlink.net

Curriculum vitae (PDF)

Research Interests:

The majority of previous investigations in cardiac cell signaling have focused on the characterization of individual proteins that may be essential for the production of a myocardial phenotype. In this regard, the e isoform of protein kinase C (PKC) has been identified as a central signaling element in the genesis of cardiac protection against ischemia. However, the cast of molecules participating in PKC-mediated cardiac protection has never been systematically characterized. In addition, the detailed infrastructure of PKC-dependent signaling system remains virtually unknown.

Our laboratory has recently designed and implemented a novel functional proteomic platform for the characterization of PKC signaling system in the heart. Rather than examining a single molecule in isolation, functional proteomic strategies enable an unbiased investigation of multiple signaling molecules and their protein-protein interactions in parallel, and thereby, provide a holistic portrait of the entire signaling system. We found that PKC forms multi-protein complexes and that these complexes are dynamically regulated in the normal myocardium and in the myocardium protected against ischemic insult. Furthermore, we have delineated several signaling modules within these PKC multi-protein complexes. Importantly, our data suggest that these signaling modules carry out discrete cellular tasks during cardiac protection.

We further hypothesize that the cardiac proteome is constructed on the basis of many integrated functional sub-proteomes, each of which is responsible for the manifestation of a unique biological function in the heart. So far, the sub-proteome defined by PKC complexes has been characterized by our laboratory to contain at least 93 proteins. The long term goal of the laboratory is to characterize the roles of all proteins within the PKC signaling system in the heart on four fundamental levels: 1) spatial localization; 2) temporal regulation; 3) expression and post-translational modification; and 4) functional importance. This will include the generation of cell culture and live animal models to verify the contribution of individual molecules in the PKC sub-proteome to the phenotypes of ischemic injury and cardiac protection. In addition, we are implementing this proteomic platform to map other signaling systems important to cardiac function in health and disease.

1.Vondriska TM, Pass JM, Ping P. Scaffold proteins and assembly of multiprotein signaling complexes. J Mol Cell Cardiol. 2004 Aug;37(2):391-7.

2.Zhang J, Ping P, Wang GW, Lu M, Pantaleon D, Tang XL, Bolli R, Vondriska TM. Bmx, a member of the Tec family of non-receptor tyrosine kinases, is a novel participant in pharmacological cardioprotection. Am J Physiol Heart Circ Physiol. 2004 Jun 10 [Epub ahead of print]

3.Ping P, Baines CP, Gu Y, Prabhu SD, Zhang J, Tsai LL, Cardwell E, Zong NC, Vondriska TM, Korge P, Bhatnagar A, Wang GW. Cardiac toxic effects of trans-2-hexenal are mediated by induction of cardiomyocyte apoptotic pathways. Cardiovasc Toxicol. 2003;3(4):341-51.

4.Doble BW, Dang X, Ping P, Fandrich RR, Nickel BE, Jin Y, Cattini PA, Kardami E. Phosphorylation of serine 262 in the gap junction protein connexin-43 regulates DNA synthesis in cell-cell contact forming cardiomyocytes. J Cell Sci. 2004 Jan 26;117(Pt 3):507-14.

5.Prabhu SD, Wang G, Luo J, Gu Y, Ping P, Chandrasekar B. Beta-adrenergic receptor blockade modulates Bcl-X(S) expression and reduces apoptosis in failing myocardium. J Mol Cell Cardiol. 2003 May;35(5):483-93.

6.Wang JF, Yang Y, Wang G, Min J, Sullivan MF, Ping P, Xiao YF, Morgan JP. Embryonic stem cells attenuate viral myocarditis in murine model. Cell Transplant. 2002;11(8):753-8.

7. Ping P. Identification of novel signaling complexes by functional proteomics. Circ Res. 2003;93:595-603.

8. Vondriska TM, Ping P. Multiprotein signaling complexes and regulation of cardiac phenotype. J Mol Cell Cardiol. 2003;35:1027-33.

9. Weiss JN, Korge P, Honda HM, Ping P. Role of the mitochondrial permeability transition in myocardial disease. Circ Res. 2003;93:292-301.

10. Pass JM, Zhang J, Vondriska TM, Ping P. Functional proteomic analysis of the protein kinase C signaling system. Methods Mol Biol. 2003;233:369-85.

11. Ping P. A new chapter in cardiac PKC signaling studies: searching for isoform-specific molecular targets. Focus on: "isoenzyme-selective regulation of SERCA2 gene expression by protein kinase C in neonatal rat ventricular myocytes". Am J Physiol Cell Physiol. 2003;285:C19-21

12. Baines CP, Song CX, Guo Y, Bolli R, Wang O-L, Zheng Y-T, Xiu JX, Cardwell EM, Ping P. Protein kinase C interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res. 2003 May 2;92(8):873-80.

13. Tang XL, Kodani E, Takano H, Hill M, Shinmura K, Vondriska TM, Ping P, Bolli R. Protein tyrosine kinase signaling is necessary for nitric oxide donor-induced late preconditioning against myocardial stunning. Am J Physiol Heart Circ Physiol. 2002 Dec 12.

14. Vondriska TM, Ping P. Functional proteomics to study protection of the ischaemic myocardium. Expert Opin Ther Targets. 2002;6:563-70.

15. Edmondson RD, Vondriska TM, Biederman KJ, Zhang J, Jones RC, Zheng Y, Allen DL, Xiu JX, Cardwell EM, Pisano MR, Ping P. Protein kinase C signaling complexes include metabolism- and transcription/translation-related proteins: complimentary separation techniques with LC/MS/MS. Mol Cell Proteomics. 2002;1:421-33.

16. Doble BW, Ping P, Fandrich RR, Cattini PA, Kardami E. Protein kinase C- mediates phorbol ester-induced phosphorylation of connexin-43. Cell Adhes Commun. 2001;8:253-6.


17. Cross HR, Murphy E, Bolli R, Ping P, Steenbergen C. Expression of activated PKC epsilon (PKC) protects the ischemic heart, without attenuating ischemic H(+) production. J Mol Cell Cardiol. 2002;34:361-7.


18. Baines CP, Zhang J, Wang GW, Zheng YT, Xiu JX, Cardwell EM, Bolli R, Ping P. Mitochondrial PKC and MAPK form signaling modules in the murine heart: enhanced mitochondrial PKC-MAPK interactions and differential MAPK activation in PKC-induced cardioprotection. Circ Res. 2002;90:390-7.


19. Ping P, Song C, Zhang J, Guo Y, Cao X, Li RC, Wu W, Vondriska TM, Pass JM, Tang XL, Pierce WM, Bolli R. Formation of protein kinase C-Lck signaling modules confers cardioprotection. J Clin Invest. 2002;109:499-507.

20. Balafanova Z, Bolli R, Zhang J, Zheng Y, Pass JM, Bhatnagar A, Tang XL, Wang O, Cardwell E, Ping P. Nitric oxide (NO) induces nitration of protein kinase C epsilon (PKC), facilitating PKC enhanced PKC-RACK2 interactions: a novel mechanism of no-triggered activation of PKC. J Biol Chem. 2002;277:15021-15027.

21. Song C, Vondriska TM, Wang GW, Klein JB, Cao X, Zhang J, Kang YJ, D'Souza S, Ping P. Molecular conformation dictates signaling module formation: example of PKC and Src tyrosine kinase. Am J Physiol Heart Circ Physiol. 2002;282:H1166-71.

22. Pass JM, Gao J, Jones WK, Wead WB, Wu X, Zhang J, Baines CP, Bolli R, Zheng YT, Joshua IG, Ping P. Enhanced PKC beta II translocation and PKC beta II-RACK1 interactions in PKC epsilon-induced heart failure: a role for RACK1. Am J Physiol Heart Circ Physiol. 2001;281:H2500-10.

23. Vondriska TM, Zhang J, Song C, Tang XL, Cao X, Baines CP, Pass JM, Wang S, Bolli R, Ping P. Protein kinase C epsilon-Src modules direct signal transduction in nitric oxide-induced cardioprotection: complex formation as a means for cardioprotective signaling. Circ Res. 2001;88:1306-13.

24. Baines CP, Pass JM, Ping P. Protein kinases and kinase-modulated effectors in the late phase of ischemic preconditioning. Basic Res Cardiol. 2001;96:207-18.

25. Vondriska TM, Klein JB, Ping P. Use of functional proteomics to investigate PKC epsilon-mediated cardioprotection: the signaling module hypothesis. Am J Physiol Heart Circ Physiol. 2001;280:H1434-41.

26. Pass JM, Zheng Y, Wead WB, Zhang J, Li RC, Bolli R, Ping P. PKCepsilon activation induces dichotomous cardiac phenotypes and modulates PKCepsilon-RACK interactions and RACK expression. Am J Physiol Heart Circ Physiol. 2001;280:H946-55.

27. Ping P, Zhang J, Pierce WM Jr, Bolli R. Functional proteomic analysis of protein kinase C epsilon signaling complexes in the normal heart and during cardioprotection. Circ Res. 2001;88:59-62.

28. Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, Ping P, McLeish KR. p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils. J Biol Chem. 2001;276:3517-23.

29. Li RC, Ping P, Zhang J, Wead WB, Cao X, Gao J, Zheng Y, Huang S, Han J, Bolli R. PKCepsilon modulates NF-kappaB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes. Am J Physiol Heart Circ Physiol. 2000;279:H1679-89.

30. Takeishi Y, Ping P, Bolli R, Kirkpatrick DL, Hoit BD, Walsh RA. Transgenic overexpression of constitutively active protein kinase C epsilon causes concentric cardiac hypertrophy. Circ Res. 2000;86:1218-23.

31. Ping P, Murphy E. Role of p38 mitogen-activated protein kinases in preconditioning: a detrimental factor or a protective kinase? Circ Res. 2000;86:921-2.

32. Doble BW, Ping P, Kardami E The epsilon subtype of protein kinase C is required for cardiomyocyte connexin-43 phosphorylation. Circ Res. 2000;86:293-301.

33. Dawn B, Xuan YT, Qiu Y, Takano H, Tang XL, Ping P, Banerjee S, Hill M, Bolli R. Bifunctional role of protein tyrosine kinases in late preconditioning against myocardial stunning in conscious rabbits. Circ Res. 1999;85:1154-63.

34. Ping P, Zhang J, Huang S, Cao X, Tang XL, Li RC, Zheng YT, Qiu Y, Clerk A, Sugden P, Han J, Bolli R. PKC-dependent activation of p46/p54 JNKs during ischemic preconditioning in conscious rabbits. Am J Physiol. 1999;277:H1771-85.

35. Guo Y, Jones WK, Xuan YT, Tang XL, Bao W, Wu WJ, Han H, Laubach VE, Ping P, Yang Z, Qiu Y, Bolli R. The late phase of ischemic preconditioning is abrogated by targeted disruption of the inducible NO synthase gene. Proc Natl Acad Sci USA. 1999;96:11507-12.

36. Ping P, Zhang J, Zheng YT, Li RC, Dawn B, Tang XL, Takano H, Balafanova Z, Bolli R.Demonstration of selective protein kinase C-dependent activation of Src and Lck tyrosine kinases during ischemic preconditioning in conscious rabbits. Circ Res. 1999;85:542-50.

37. Ping P, Zhang J, Cao X, Li RC, Kong D, Tang XL, Qiu Y, Manchikalapudi S, Auchampach JA, Black RG, Bolli R. PKC-dependent activation of p44/p42 MAPKs during myocardial ischemia-reperfusion in conscious rabbits. Am J Physiol. 1999;276:H1468-81.

38. Ping P, Takano H, Zhang J, Tang XL, Qiu Y, Li RC, Banerjee S, Dawn B, Balafonova Z, Bolli R. Isoform-selective activation of protein kinase C by nitric oxide in the heart of conscious rabbits: a signaling mechanism for both nitric oxide-induced and ischemia-induced preconditioning. Circ Res. 1999;84:587-604.

39. Bolli R, Dawn B, Tang XL, Qiu Y, Ping P, Xuan YT, Jones WK, Takano H, Guo Y, Zhang J. The nitric oxide hypothesis of late preconditioning. Basic Res Cardiol. 1998;93:325-38.

40. Qiu Y, Ping P, Tang XL, Manchikalapudi S, Rizvi A, Zhang J, Takano H, Wu WJ, Teschner S, Bolli R. Direct evidence that protein kinase C plays an essential role in the development of late preconditioning against myocardial stunning in conscious rabbits and that epsilon is the isoform involved. J Clin Invest. 1998;101:2182-98.

41. Gao M, Ping P, Post S, Insel PA, Tang R, Hammond HK. Increased expression of adenylylcyclase type VI proportionately increases beta-adrenergic receptor-stimulated production of cAMP in neonatal rat cardiac myocytes. Proc Natl Acad Sci USA. 1998;95:1038-43.

42. Pal M, Toth A, Ping P, Johnson PC. Capillary blood flow and tissue metabolism in skeletal muscle during sympathetic trunk stimulation. Am J Physiol. 1998;274:H430-40.

43. Hammond HK, Ping P, Insel PA. Cardiac G-protein receptor kinase activity: effect of a beta-adrenergic receptor antagonist. Adv Pharmacol. 1998;42:507-10.

44. Ping P, Zhang J, Qiu Y, Tang XL, Manchikalapudi S, Cao X, Bolli R. Ischemic preconditioning induces selective translocation of protein kinase C isoforms epsilon and eta in the heart of conscious rabbits without subcellular redistribution of total protein kinase C activity. Circ Res. 1997;81:404-14.

45. Ping P, Anzai T, Gao M, Hammond HK. Adenylyl cyclase and G protein receptor kinase expression during development of heart failure. Am J Physiol. 1997;273:H707-17.

46. Ping P, Yang Q, Hammond HK. Altered beta-adrenergic receptor signaling in heart failure, in vivo gene transfer via adeno and adeno-associated virus. Microcirculation. 1996;3:225-8.

47. Giordano FJ, Ping P, McKirnan MD, Nozaki S, DeMaria AN, Dillmann WH, Mathieu-Costello O, Hammond HK. Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart. Nat Med. 1996;2:534-9.

48. Ping P, Gelzer-Bell R, Roth DA, Kiel D, Insel PA, Hammond HK. Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart. J Clin Invest. 1995;95:1271-80.

49. Ping P, Hammond HK. Diverse G protein and beta-adrenergic receptor mRNA expression in normal and failing porcine hearts. Am J Physiol. 1994;267:H2079-85.

50. Ping P, Johnson PC. Arteriolar network response to pressure reduction during sympathetic nerve stimulation in cat skeletal muscle. Am J Physiol. 1994;266:H1251-9.

51. Hammond HK, Roth DA, McKirnan MD, Ping P. Regional myocardial downregulation of the inhibitory guanosine triphosphate-binding protein (Gi alpha 2) and beta-adrenergic receptors in a porcine model of chronic episodic myocardial ischemia. J Clin Invest. 1993;92:2644-52.

52. Ping P, Faber JE. Characterization of alpha-adrenoceptor gene expression in arterial and venous smooth muscle. Am J Physiol. 1993;265:H1501-9.

53. Ping P, Johnson PC. Role of myogenic response in enhancing autoregulation of flow during sympathetic nerve stimulation. Am J Physiol. 1992;263:H1177-84.

54. Ping P, Johnson PC. Mechanism of enhanced myogenic response in arterioles during sympathetic nerve stimulation. Am J Physiol. 1992;263:H1185-9.