Ying Ge, PhD

Portrait of Ying Ge, PhD
Assistant Professor
Cell and Regenerative Biology
Email: 
Address: 
130 SMI
470 N Charter Street
Madison, WI 53706
Telephone: 
(608) 263-9212
Focus Groups: 
Signal Transduction
Education: 
PhD, Cornell University
Research Summary: 
Cardiovascular Systems Biology through High-resolution Mass Spectrometry-based Comparative Proteomics and Metabolomics
Research Detail: 

My research aims to understand the molecular and cellular mechanisms underlying cardiovascular diseases via systems biology approaches featuring cutting-edge ultra high-resolution mass spectrometry (MS)-based comparative proteomics and metabolomics in conjunction with functional studies. Cardiovascular disease is the leading cause of morbidity and mortality in developed countries and is reaching epidemic proportions. Transformative insights from a holistic approach at the systems level have great potential to elucidate disease mechanisms and to develop new therapeutic treatments. Proteins and metabolites are important molecular entities of the cell downstream of genes. Hence in the post genomic era, proteomics and metabolomics (the large-scale global analysis of proteins and metabolites in a cell, organism, tissue, and biofluid) are essential for deciphering how molecules interact as a system and for understanding the functions of cellular systems in health and disease. However, there are tremendous challenges in proteomics and metabolomics due to the extreme complexity and dynamic nature of the proteome and metabolome. To address such challenges, we are developing novel ultra high-resolution MS-based top-down comparative proteomics and metabolomics platforms for systems biology studies with high efficiency, specificity, sensitivity, and reproducibility. We globally identify, characterize, and quantify intact proteins and metabolites extracted from tissues/cells/biofluids and reveal all changes in the proteome and metabolome in response to extrinsic and intrinsic stresses. We then employ these technology platforms to study cardiovascular diseases in conjunction with biochemical and physiological functional assays.

Currently I am focused on two major directions:

  1. Cardiac myofilaments: establish a global map of myofilament protein modifications under normal and diseased conditions by top-down comparative proteomics and determine the functional consequence of novel modifications in regulating cardiac contractility;
  2. Cardiac regenerative biology: evaluate the efficacy of stem cell therapies for treatment of heart failure using integrated proteomics and metabolomics approaches and understand the paracrine signaling mechanism in cardiac regeneration.

 

My research is highly interdisciplinary within the interface of chemistry, biology, and medicine. Success in my proposed research will advance our understanding of the molecular basis of diseases and foster the development of new strategies for early diagnosis, prevention and better treatment of cardiovascular diseases.

Selected Publications: 
Monophosphorylation of cardiac troponin-I at Ser23/24 is sufficient to regulate cardiac myofibrillar Ca2+ sensitivity and calpain-induced proteolysis. Martin-Garrido A, Biesiadecki BJ, Salhi HE, Shaifta Y, Dos Remedios CG, Ayuz-GunerS, Cai W, Ge Y, Avkiran M, Kentish JC. J Biol Chem. 2018 Apr 18. pii: jbc.RA117.001292. doi: 10.1074/jbc.RA117.001292. [Epub ahead of print] PMID: 29669813
Comprehensive Characterization of Swine Cardiac Troponin T Proteoforms by Top-Down Mass Spectrometry. Lin Z, Guo F, Gregorich ZR, Sun R, Zhang H, Hu Y, Shanmuganayagam D, Ge Y. J Am Soc Mass Spectrom. 2018 Apr 9. doi: 10.1007/s13361-018-1925-y. [Epub ahead of print] PMID: 29633223
Harnessing the Power of Proteomics to Assess Drug Safety and Guide Clinical Trials. Lam MPY, Ge Y. Circulation. 2018 Mar 6;137(10):1011-1014. doi: 10.1161/CIRCULATIONAHA.117.032876. No abstract available. PMID: 29506994
The HCM-linked W792R mutation in cardiac myosin binding protein-C reduces C6 FnIII domain stability. Smelter DF, De Lange WJ, Cai W, Ge Y, Ralphe JC. Am J Physiol Heart Circ Physiol. 2018 Feb 16. doi: 10.1152/ajpheart.00686.2017. [Epub ahead of print] PMID: 29451820
How many human proteoforms are there? Aebersold R, Agar JN, Amster IJ, Baker MS, Bertozzi CR, BojaES, Costello CE, Cravatt BF, Fenselau C, Garcia BA, Ge Y, Gunawardena J, Hendrickson RC, Hergenrother PJ, Huber CG, Ivanov AR, Jensen ON, Jewett MC, Kelleher NL, Kiessling LL, Krogan NJ, Larsen MR, Loo JA, Ogorzalek Loo RR, Lundberg E, MacCoss MJ, MallickP, Mootha VK, Mrksich M, Muir TW, Patrie SM, Pesavento JJ, Pitteri SJ, Rodriguez H, Saghatelian A, Sandoval W, Schlüter H, Sechi S, Slavoff SA, Smith LM, Snyder MP, Thomas PM, Uhlén M, Van Eyk JE, Vidal M, Walt DR, White FM, Williams ER, Wohlschlager T, Wysocki VH, Yates NA, Young NL, Zhang B. Nat Chem Biol. 2018 Feb 14;14(3):206-214. doi: 10.1038/nchembio.2576. PMID: 29443976
Characterization of TTN Novex Splicing Variants across Species and the Role of RBM20 in Novex-Specific Exon Splicing. Chen Z, Song J, Chen L, Zhu C, Cai H, Sun M, Stern A, Mozdziak P, Ge Y, Means WJ, Guo W. Genes (Basel). 2018 Feb 13;9(2). pii: E86. doi: 10.3390/genes9020086. PMID: 29438341
ProForma: A Standard Proteoform Notation. LeDuc RD, Schwämmle V, Shortreed MR, Cesnik AJ, Solntsev SK, Shaw JB, Martin MJ, Vizcaino JA, Alpi E, Danis P, Kelleher NL, Smith LM, Ge Y, Agar JN, Chamot-Rooke J, Loo JA, Pasa-Tolic L, Tsybin YO. J Proteome Res. 2018 Mar 2;17(3):1321-1325. doi: 10.1021/acs.jproteome.7b00851. Epub 2018 Feb 14. PMID: 29397739
Trace derivatives of kynurenine potently activate the aryl hydrocarbon receptor (AHR). Seok SH, Ma ZX, Feltenberger JB, Chen H, Chen H, Scarlett C, Lin Z, Satyshur KA, Cortopassi M, Jefcoate CR, Ge Y, Tang W, Bradfield CA, Xing Y. J Biol Chem. 2018 Feb 9;293(6):1994-2005. doi: 10.1074/jbc.RA117.000631. Epub 2017 Dec 26. PMID: 29279331
Large Cardiac Muscle Patches Engineered From Human Induced-Pluripotent Stem Cell-Derived Cardiac Cells Improve Recovery From Myocardial Infarction in Swine. Gao L, GregorichZR, Zhu W, Mattapally S, Oduk Y, Lou X, Kannappan R, Borovjagin AV, Walcott GP, Pollard AE, Fast VG, Hu X, Lloyd SG, Ge Y, Zhang J. Circulation. 2018 Apr 17;137(16):1712-1730. doi: 10.1161/CIRCULATIONAHA.117.030785. Epub 2017 Dec 12. PMID: 29233823
Top-Down Proteomics: Ready for Prime Time? Chen B, Brown KA, Lin Z, Ge Y. Anal Chem. 2018 Jan 2;90(1):110-127. doi: 10.1021/acs.analchem.7b04747. Epub 2017 Dec 15. No abstract available. PMID: 29161012