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Protein ArrayOne D GelConfocal
 
 

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

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

  

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.
     
   

Publications:

  1. Abdellatif AA, Pelt JL, Benton RL, Howard RM, Tsoulfas P, Ping P , Xu XM, Whittemore, SR. Gene delivery to the spinal cord: comparison between lentiviral, adenoviral, and retroviral vector delivery systems." J Neurosci Res 2006; 84 :553-67.

  2.  Gomes AV, Zong C, Edmondson RD, Li X, Stefani E, Zhang J, Jones RC, Thyparambil S, Wang GW, Qiao X, Bardag-Gorce F, Ping P . Mapping the murine cardiac 26S proteasome complexes. Circ Res 2006; 99 :362-71.

  3. Gomes AV, Zong C, Ping P . Protein Degradation by the 26S Proteasome System in the Normal and Stressed Myocardium. Antioxid Redox Signal 2006; 8 :1677-91.

  4. Li Q, Ping P , Jiang H, Liu K. Nerve conduit filled with GDNF gene-modified Schwann cells enhances regeneration of the peripheral nerve. Microsurgery 2006; 26 :116-21.

  5. Mayr M, Zhang J, Greene AS, Gutterman DD, Perloff JK, Ping P . Proteomic based development of biomarkers in cardiovascular disease: Mechanistic, clinical, and therapeutic insights. Mol Cell Proteomics 2006;5:1853-1864.

  6. Orchard S, Ping P . HUPO Publications Committee Meeting: 21 April 2006 , San Francisco , CA , USA . Proteomics 2006; 6 :4436-8.

  7. Zong C, Gomes AV, Drews O, Li X, Young GW, Berhane B, Qiao X, French SW, Bardag-Gorce F, Ping P . Regulation of murine cardiac 20S proteasomes: role of associating partners. Circ Res 2006; 99 :372-80.

  8. Berhane BT, Zong C, Liem DA, Huang A, Le S, Edmondson RD, Jones RC, Qiao X, Whitelegge JP, Ping P , Vondriska TM. Cardiovascular-related proteins identified in human plasma by the HUPO Plasma Proteome Project pilot phase. Proteomics 2005; 5 :3520-30.

  9. Cao Q, Xu XM, Devries WH, Enzmann GU, Ping P , Tsoulfas P, Wood PM, Bunge MB, Whittemore SR. Functional recovery in traumatic spinal cord injury after transplantation of multineurotrophin-expressing glial-restricted precursor cells. J Neurosci 2005; 25 :6947-57.

  10. Gomes AV, Zong C, Edmondson RD, Berhane BT, Wang GW, Le S, Young G, Zhang J, Vondriska TM, Whitelegge JP, Jones RC, Joshua IG, Thyparambil S, Pantaleon, D, Qiao J, Loo J, Ping P . The murine cardiac 26S proteasome: an organelle awaiting exploration. Ann N Y Acad Sci 2005; 1047 :197-207.

  11. McCarthy J, McLeod CJ, Minners J, Essop MF, Ping P , Sack MN . PKCepsilon activation augments cardiac mitochondrial respiratory post-anoxic reserve--a putative mechanism in PKCepsilon cardioprotection. J Mol Cell Cardiol 2005; 38 :697-700.

  12. Omenn GS, Ping P . HUPO 3rd annual World Congress on Proteomics. 25- 27th October, 2004 , Beijing , China . Expert Rev Proteomics 2005; 2 :9-12.

  13. Omenn GS, States DJ, Adamski M, Blackwell TW, Menon R, Hermjakob H, Apweiler R, Haab BB, Simpson RJ, Eddes JA, Kapp EA, Moritz RL, Chan DW, Rai AJ, Admon A, Aebersold R, Eng J, Hancock WS, Hefta SA, Meyer H, Paik YK, Yoo JS, Ping P , Pounds J, Adkins J, Qian X, Wang R, Wasinger V, Wu CY, Zhao X, Zeng R, Archakov A, Tsugita A, Beer I, Pandey A, Pisano M, Andrews P, Tammen H, Speicher DW, Hanash SM. Overview of the HUPO Plasma Proteome Project: results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-available database. Proteomics 2005; 5 :3226-45.

  14. Ping P , Vondriska TM, Creighton CJ, Gandhi TK, Yang Z, Menon R, Kwon, MS, Cho SY, Drwal G, Kellmann M, Peri S, Suresh S, Gronborg M, Molina H, Chaerkady R, Rekha B, Shet AS, Gerszten RE, Wu H, Raftery M, Wasinger V, Schulz-Knappe P, Hanash SM, Paik YK, Hancock WS, States DJ, Omenn GS, Pandey A. A functional annotation of subproteomes in human plasma. Proteomics 2005; 5 :3506-19.

  15. W, Chen X, Jing X. Poly(epsilon-caprolactone) polyurethane and its shape-memory property. Biomacromolecules 2005; 6 :587-92.

  16. Wang G, Liem DA, Vondriska TM, Honda HM, Korge P, Pantaleon DM, Qiao X, Wang Y, Weiss JN, Ping P . Nitric oxide donors protect murine myocardium against infarction via modulation of mitochondrial permeability transition. Am J Physiol Heart Circ Physiol 2005; 288 :H1290-5.

  17. Zhang J, Baines CP, Zong C, Cardwell EM, Wang G, Vondriska TM, Ping P . Functional proteomic analysis of a three-tier PKCepsilon-Akt-eNOS signaling module in cardiac protection. Am J Physiol Heart Circ Physiol 2005; 288 :H954-61.

  18. 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; 117 :507-14.

  19. MacLellan WR, Ping P , Vondriska T. Heart disease leaves its mark: proteomics-based biosignatures in acute coronary syndromes. J Am Coll Cardiol 2004; 44 :1584-6.

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

  21. Zhang J, Ping P , Wang GW, Lu M, Pantaleon D, Tang XL, Bolli R, Vondriska TM. Bmx, a member of the Tec family of nonreceptor tyrosine kinases, is a novel participant in pharmacological cardioprotection. Am J Physiol Heart Circ Physiol 2004; 287 :H2364-6.

  22. Baines CP, Song CX, Zheng YT, Wang GW, Zhang J, Wang OL, Guo Y, Bolli R, Cardwell EM, Ping P . Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res 2003; 92 :873-80.

  23. 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.

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

  25. 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.

  26. Ping P , Baines CP, Gu Y, Prabhu SD, Zhang J, Tsai LL, Cardwell E, Zong C, 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 :341-51.

  27. 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; 35 :483-93.

  28. Tang XL, Kodani E, Takano H, Hill M, Shinmura K, Vondriska TM, Ping P , Bolli R. Protein tyrosine kinase signaling is necessary for NO donor-induced late preconditioning against myocardial stunning. Am J Physiol Heart Circ Physiol 2003; 284 :H1441-8.

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

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

  31. Zhang J, Ping P , Vondriska TM, Tang XL, Wang GW, Cardwell EM, Bolli R. Cardioprotection involves activation of NF-kappa B via PKC-dependent tyrosine and serine phosphorylation of I kappa B-alpha. Am J Physiol Heart Circ Physiol 2003; 285 :H1753-8.

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

  33. 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 Cepsilon (PKCepsilon ), facilitating PKCepsilon translocation via enhanced PKCepsilon -RACK2 interactions: a novel mechanism of no-triggered activation of PKCepsilon. J Biol Chem 2002; 277 :15021-7.

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

  35. 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 epsilon signaling complexes include metabolism- and transcription/translation-related proteins: complimentary separation techniques with LC/MS/MS. Mol Cell Proteomics 2002; 1 :421-33.

  36. 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(epsilon)-Lck signaling modules confers cardioprotection. J Clin Invest 2002; 109 :499-507.

  37. 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 PKCepsilon and Src tyrosine kinase. Am J Physiol Heart Circ Physiol 2002; 282 :H1166-71.

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

  39. 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 :753-8.

  40. 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.

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

  42. Pass JM , Gao J, Jones WK , Wead WB , Wu, X., Zhang, J., Baines, C. P., Bolli, R., Zheng, Y. T., Joshua, I. G. and Ping, P . (2001). "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 281 (6): H2500-10.

  43. Pass, J. M., Zheng, Y., Wead, W. B., Zhang, J., Li, R. C., Bolli, R. and Ping, P . (2001). "PKCepsilon activation induces dichotomous cardiac phenotypes and modulates PKCepsilon-RACK interactions and RACK expression." Am J Physiol Heart Circ Physiol 280 (3): H946-55.

  44. Ping, P ., Zhang, J., Pierce, W. M., Jr. and Bolli, R. (2001). "Functional proteomic analysis of protein kinase C epsilon signaling complexes in the normal heart and during cardioprotection." Circ Res 88 (1): 59-62.

  45. Rane, M. J., Coxon, P. Y., Powell, D. W., Webster, R., Klein, J. B., Pierce, W., Ping, P . and McLeish, K. R. (2001). "p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils." J Biol Chem 276 (5): 3517-23.

  46. Vondriska, T. M., Klein, J. B. and Ping, P . (2001). "Use of functional proteomics to investigate PKC epsilon-mediated cardioprotection: the signaling module hypothesis." Am J Physiol Heart Circ Physiol 280 (4): H1434-41.

  47. Vondriska, T. M., Zhang, J., Song, C., Tang, X. L., Cao, X., Baines, C. P., Pass, J. M., Wang, S., Bolli, R. and Ping, P . (2001). "Protein kinase C epsilon-Src modules direct signal transduction in nitric oxide-induced cardioprotection: complex formation as a means for cardioprotective signaling." Circ Res 88 (12): 1306-13.

  48. Doble, B. W., Ping, P . and Kardami, E. (2000). "The epsilon subtype of protein kinase C is required for cardiomyocyte connexin-43 phosphorylation." Circ Res 86 (3): 293-301.

  49. Li, R. C., Ping, P ., Zhang, J., Wead, W. B., Cao, X., Gao, J., Zheng, Y., Huang, S., Han, J. and Bolli, R. (2000). "PKCepsilon modulates NF-kappaB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes." Am J Physiol Heart Circ Physiol 279 (4): H1679-89.

  50. Ping, P ., Li, Q. F. and Gan, J. L. (2000). "[Neurobiological effect of nerve regeneration conditioned fluid on motoneuron]." Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 14 (6): 325-7.

  51. Ping, P . and Murphy, E. (2000). "Role of p38 mitogen-activated protein kinases in preconditioning: a detrimental factor or a protective kinase?" Circ Res 86 (9): 921-2.

  52. Takeishi, Y., Ping, P ., Bolli, R., Kirkpatrick, D. L., Hoit, B. D. and Walsh, R. A. (2000). "Transgenic overexpression of constitutively active protein kinase C epsilon causes concentric cardiac hypertrophy." Circ Res 86 (12): 1218-23.

  53. Dawn, B., Xuan, Y. T., Qiu, Y., Takano, H., Tang, X. L., Ping, P ., Banerjee, S., Hill, M. and Bolli, R. (1999). "Bifunctional role of protein tyrosine kinases in late preconditioning against myocardial stunning in conscious rabbits." Circ Res 85 (12): 1154-63.

  54. Guo, Y., Jones, W. K., Xuan, Y. T., Tang, X. L., Bao, W., Wu, W. J., Han, H., Laubach, V. E., Ping, P ., Yang, Z., Qiu, Y. and Bolli, R. (1999). "The late phase of ischemic preconditioning is abrogated by targeted disruption of the inducible NO synthase gene." Proc Natl Acad Sci U S A 96 (20): 11507-12.

  55. Ping, P ., Takano, H., Zhang, J., Tang, X. L., Qiu, Y., Li, R. C., Banerjee, S., Dawn, B., Balafonova, Z. and Bolli, R. (1999). "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 84 (5): 587-604.

  56. Ping, P ., Zhang, J., Cao, X., Li, R. C., Kong, D., Tang, X. L., Qiu, Y., Manchikalapudi, S., Auchampach, J. A., Black, R. G. and Bolli, R. (1999). "PKC-dependent activation of p44/p42 MAPKs during myocardial ischemia-reperfusion in conscious rabbits." Am J Physiol 276 (5 Pt 2): H1468-81.

  57. Ping, P ., Zhang, J., Huang, S., Cao, X., Tang, X. L., Li, R. C., Zheng, Y. T., Qiu, Y., Clerk, A., Sugden, P., Han, J. and Bolli, R. (1999). "PKC-dependent activation of p46/p54 JNKs during ischemic preconditioning in conscious rabbits." Am J Physiol 277 (5 Pt 2): H1771-85.

  58. Ping, P ., Zhang, J., Zheng, Y. T., Li, R. C., Dawn, B., Tang, X. L., Takano, H., Balafanova, Z. and Bolli, R. (1999). "Demonstration of selective protein kinase C-dependent activation of Src and Lck tyrosine kinases during ischemic preconditioning in conscious rabbits." Circ Res 85 (6): 542-50.

  59. Bolli, R., Dawn, B., Tang, X. L., Qiu, Y., Ping, P ., Xuan, Y. T., Jones, W. K., Takano, H., Guo, Y. and Zhang, J. (1998). "The nitric oxide hypothesis of late preconditioning." Basic Res Cardiol 93 (5): 325-38.

  60. Gao, M., Ping, P ., Post, S., Insel, P. A., Tang, R. and Hammond, H. K. (1998). "Increased expression of adenylylcyclase type VI proportionately increases beta-adrenergic receptor-stimulated production of cAMP in neonatal rat cardiac myocytes." Proc Natl Acad Sci U S A 95 (3): 1038-43.

  61. Hammond, H. K., Ping, P . and Insel, P. A. (1998). "Cardiac G-protein receptor kinase activity: effect of a beta-adrenergic receptor antagonist." Adv Pharmacol 42 : 507-10.

  62. Pal, M., Toth, A., Ping, P . and Johnson, P. C. (1998). "Capillary blood flow and tissue metabolism in skeletal muscle during sympathetic trunk stimulation." Am J Physiol 274 (2 Pt 2): H430-40.

  63. Qiu, Y., Ping, P ., Tang, X. L., Manchikalapudi, S., Rizvi, A., Zhang, J., Takano, H., Wu, W. J., Teschner, S. and Bolli, R. (1998). "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 101 (10): 2182-98.

  64. Ping, P ., Anzai, T., Gao, M. and Hammond, H. K. (1997). "Adenylyl cyclase and G protein receptor kinase expression during development of heart failure." Am J Physiol 273 (2 Pt 2): H707-17.

  65. Ping, P ., Zhang, J., Qiu, Y., Tang, X. L., Manchikalapudi, S., Cao, X. and Bolli, R. (1997). "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 81 (3): 404-14.

  66. Giordano, F. J., Ping, P ., McKirnan, M. D., Nozaki, S., DeMaria, A. N., Dillmann, W. H., Mathieu-Costello, O. and Hammond, H. K. (1996). "Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart." Nat Med 2 (5): 534-9.

  67. Ping, P ., Yang, Q. and Hammond, H. K. (1996). "Altered beta-adrenergic receptor signaling in heart failure, in vivo gene transfer via adeno and adeno-associated virus." Microcirculation 3 (2): 225-8.

  68. Ping, P ., Gelzer-Bell, R., Roth, D. A., Kiel, D., Insel, P. A. and Hammond, H. K. (1995). "Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart." J Clin Invest 95 (3): 1271-80.

  69. Ping, P . and Hammond, H. K. (1994). "Diverse G protein and beta-adrenergic receptor mRNA expression in normal and failing porcine hearts." Am J Physiol 267 (5 Pt 2): H2079-85.

  70. Ping, P . and Johnson, P. C. (1994). "Arteriolar network response to pressure reduction during sympathetic nerve stimulation in cat skeletal muscle." Am J Physiol 266 (3 Pt 2): H1251-9.

  71. Hammond, H. K., Roth, D. A., McKirnan, M. D. and Ping, P . (1993). "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 92 (6): 2644-52.

  72. Ping, P . and Faber, J. E. (1993). "Characterization of alpha-adrenoceptor gene expression in arterial and venous smooth muscle." Am J Physiol 265 (5 Pt 2): H1501-9.

  73. Ping, P . and Johnson, P. C. (1992). "Mechanism of enhanced myogenic response in arterioles during sympathetic nerve stimulation." Am J Physiol 263 (4 Pt 2): H1185-9.

  74. Ping, P . and Johnson, P. C. (1992). "Role of myogenic response in enhancing autoregulation of flow during sympathetic nerve stimulation." Am J Physiol 263 (4 Pt 2): H1177-84.
 
 
 
       
     
 
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