Research Summary

Dr. Ping’s current research program focuses on the understanding of proteome biology in cardiovascular medicine, with a particular interest on alterations of subproteomes encoding signaling pathways and cellular organelles during cardiac pathogenesis. Her research group investigates specific areas in:

1. Mitochondrial Biology in the Heart:
   Cardiac mitochondria proteome and phosphoproteome: The subproteome composition and post-translational modification profiles define the functional state of the cardiac mitochondria. My group employs state-of-the-art mass spectrometry expertise to interrogate their dynamics in health and diseases. Mitochondrial proteome turnover: The body of mitochondrial proteome is continuously replaced. Such kinetics varies greatly among distinct proteins and even for the same protein under different pathophysiological states. A novel strategy to systematically characterize their perturbations has been devised in our research group. Mitochondrial permeability transition (MPT): MPT is caused by the opening of permeability transition pores in the inner mitochondrial membrane and may lead to cell death. A multi-disciplinary approach using an array of omics tools is applied to characterize MPT regulation (i.e., their interacting partners) in the healthy and diseased myocardium.
    

2. Proteasome Biology in the Heart:
   Proteasome function: Our research group has established necessary toolboxes for the investigation of ubiquitin-proteasome-dependent degradation of proteins in the heart. We combine both biochemical and proteomic technologies to investigate 20S and 26S proteasome complexes in the normal, protected, and diseased heart. Proteasome heterogeneity: A heterogenic population of proteasome complexes exists in the heart, the composition of which is subject to change upon stress. A powerful technical platform has been assembled to characterize each subpopulation individually with its native constituents, which enables us to pinpoint specific changes. Proteasome regulation by post-translational modifications: The functional dynamics of the proteasome complexes are regulated via various forms of post-translational modifications.
    

3. Cardiac Organellar Protein atlas Knowledgebase (COPaKB): We have developed a COPa knowledgebase, a specialized resource for cardiac proteome biology. It integrates orthogonal sets of proteome knowledge and biomedical insights into context, while providing bioinformatics tools and web portals to efficiently disseminate proteomics proficiencies. It bridges data-driven proteomic discoveries and hypothesis-driven investigations, facilitates synergistic research paradigm across the research community, thereby advancing cardiovascular biology and medicine.

Representative Publications

1. Deng N, Zhang J, Zong C, Wang Y, Lu H, Yang P, Wang W, Young GW, Wang Y, Korge P, Lotz C, Doran P, Liem DA, Apweiler R, Weiss JN, Duan H, Ping P. Phosphoproteome Analysis Reveals Regulatory Sites in Major pathways of Cardiac Mitochondria. Mol Cell Proteomics. 2011;10:M110.000117

2. Ping P. Getting to the Heart of Proteomics. New Eng J Med. 2009; 360: 532-534.

3. 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;99:372-380.

4. Gomes AV, Zong C, Edmondson RD, Li X, Stefani E, Zhang J, Jones RC, Thyparambil S, Ping P. Mapping the murine cardiac 26S proteasome complexes. Circ Res. 2006; 99:362-371.

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

6. Edmondson RD, Vondriska TM, Biederman KJ, Zhang J, Jones RC, Pisano MR, Ping P. PKC complexes include metabolic- and translation-related proteins. Mol Cell Proteomics. 2002;1:421-433.

7. Baines CP, Zhang J, Wang GW, Zheng YT, Xiu JX, Cardwell EM, Bolli R, Ping P. Mitochondrial PKC and MAPK form signaling modules. Circ Res. 2002;90:390-397.

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

9. Ping P, Zhang J, Pierce W, Bolli R. Functional proteomic analysis of PKCε signaling complexes in the normal heart and during cardioprotection. Circ Res. 2001;88:59-62.

10. Ping P, Takano H, Zhang J, Tang XL, Qiu Y, Li R, Banerjee S, Dawn B, Bolli R. Isoform-selective activation of PKCε by nitric oxide in the heart of conscious rabbits. Circ Res. 1999;84:587-604.

11. Ping P, Zhang J, Zheng YT, Li R, Dawn B, Takano H, Balafanova Z, Bolli R. Demonstration of PKCε-dependent activation of Src and Lck tyrosine kinases in preconditioning. Circ Res. 1999;85:542-50.

12. Ping P, Qiu Y, Zhang J, Tang XL, Manchikalapudi S, Bolli R. Direct evidence for an essential role of PKC in the development of late preconditioning in rabbits. J Clin Invest 1998;101:2182-2198.

13. Ping P, Gao M, Post S, Insel PA, Tang R, Hammond HK. Increased expression of adenylylcyclase type VI proportionately increases β-adrenergic receptor-stimulated cAMP in neonatal rat cardiac myocytes. Proc Natl Acad Sci USA 1998;95:1038-1043.

14. Ping P, Zhang J, Qiu Y, Tang XL, Cao X, Bolli R. Ischemic preconditioning induces selective translocation of PKC isoform ε and  in the heart of conscious rabbits. Circ Res 1997;81:404-414.

15. Giordano F, Ping P, Mckirnan D, Nozaki S, DeMaria A, Dillmann W, 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. Nature Medicine 1996;2:534-539.
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