This Program of Excellence in Glycosciences (PEG) is comprised of 5 projects and 4 Cores, including a Shared Resources Core that contains 4 sub-core components. We have assembled a team of leading and rising star glycoscientists to not only elucidate the roles of glycoconjugates in cardiovascular disease and cardioprotection during ischemia, but also to be able to create a world-class lecture and hands-on course to train future leaders in glycoscience research focused on the missions of the NHLBI. This PEG will also focus the attention of some of the world's best research cardiologists on the roles of glycoconjugates in heart disease. The central theme of this PEG is the roles of both extracellular and intracellular glycoconjugates in the mechanisms protecting the heart or leading to atherosclerosis and cardiomyopathies, culminating in myocardial infarction and heart failure. Project 1 will investigate the roles of the crosstalk between O-GlcNAcylation and phosphorylation on cardiomyocyte mitochondrial and contractile proteins in diabetic cardiomyopathy. Project 1 will make extensive use of all of the sub-cores in Core C and will use Core D to evaluate roles of increased O-GlcNAc on cardiomyocyte physiology and functions. Project 2 will investigate the paradox that while chronic increases in O-GlcNAc cause disease, short-term increases in O-GlcNAc are cardioprotective. Project 2 will make use of all of Core C's subcores and Core D to evaluate physiological events associated with O-GlcNAc- mediated cardioprotection. Project 3 examines the hypothesis that the cell surface and secreted glycoconjugates made by cardiomyocytes and surrounding fibroblasts contribute to the micro-environment leading to eventual catastrophic heart failure and infarction. The cell surface and secretome for glycoproteins and glycans will be defined in hearts subjected to oxidative stress. Project 3 relies heavily on sub-core C1, interacts directly with Projects 4 and 5, and will extensively use Core D to monitor cardiac and cardiomyocyte physiology. Project 4 will elucidate the roles of cell surface and intracellular glycoproteins in pathological activation of platelets leading to ischemia, myocardial infarction and stroke. Project 4 will make use of most of Core C and will extensively interact with Project 1 on platelet intracellular glycans and signaling. Project 5 will investigate the roles of glycosphinoglipids in the progression of athersclerosis leading to Ml and heart failure. Project 5 will extensively use sub-cores C1, C3 and Core D, and will directly interact with Project 3. Not only will all of the Projects and Cores lead to a synergistic program that will greatly expand our knowledge of the roles of glycoconjugates in the molecular and cellular processes leading to heart attacks and heart failure, but also they all will synergistically help create a broad and deep training environment for developing the future leaders of glycoconjugate research into diseases targeted by NHLBI.

Public Health Relevance

Extracellular and intracellular glycoconjugates contribute directly to the etiology of atherosclerosis myocardial infarction and heart failure. This PEG brings a group of leading experts in glycosciences to not only elucidate the roles of glycoconjugates in these disease processes, but also to create a team qualified to lead a world-class training experience to create the next leaders in glycosciences focused on the mission of NHLBI.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel ()
Program Officer
Danthi, Narasimhan
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
Zhu, Guangshuo; Groneberg, Dieter; Sikka, Gautam et al. (2015) Soluble guanylate cyclase is required for systemic vasodilation but not positive inotropy induced by nitroxyl in the mouse. Hypertension 65:385-92
Bullen, John W; Balsbaugh, Jeremy L; Chanda, Dipanjan et al. (2014) Cross-talk between two essential nutrient-sensitive enzymes: O-GlcNAc transferase (OGT) and AMP-activated protein kinase (AMPK). J Biol Chem 289:10592-606
Wang, Xiangchun; Chen, Jing; Li, Qing Kay et al. (2014) Overexpression of ? (1,6) fucosyltransferase associated with aggressive prostate cancer. Glycobiology 24:935-44
Hardivillé, Stéphan; Hart, Gerald W (2014) Nutrient regulation of signaling, transcription, and cell physiology by O-GlcNAcylation. Cell Metab 20:208-13
Hascall, Vincent C; Wang, Aimin; Tammi, Markku et al. (2014) The dynamic metabolism of hyaluronan regulates the cytosolic concentration of UDP-GlcNAc. Matrix Biol 35:14-7
Aiyetan, Paul; Zhang, Bai; Chen, Lily et al. (2014) M2Lite: An Open-source, Light-weight, Pluggable and Fast Proteome Discoverer MSF to mzIdentML Tool. J Bioinform 1:40-49
Harlan, Robert; Zhang, Hui (2014) Targeted proteomics: a bridge between discovery and validation. Expert Rev Proteomics 11:657-61
Seo, Kinya; Rainer, Peter P; Lee, Dong-Ik et al. (2014) Hyperactive adverse mechanical stress responses in dystrophic heart are coupled to transient receptor potential canonical 6 and blocked by cGMP-protein kinase G modulation. Circ Res 114:823-32
Liu, Yansheng; Chen, Jing; Sethi, Atul et al. (2014) Glycoproteomic analysis of prostate cancer tissues by SWATH mass spectrometry discovers N-acylethanolamine acid amidase and protein tyrosine kinase 7 as signatures for tumor aggressiveness. Mol Cell Proteomics 13:1753-68
Sun, Shisheng; Zhou, Jian-Ying; Yang, Weiming et al. (2014) Inhibition of protein carbamylation in urea solution using ammonium-containing buffers. Anal Biochem 446:76-81

Showing the most recent 10 out of 40 publications