CARDIOVASCULAR INITIATIVE

Mission and Goals

Cardiovascular diseases are a leading cause of mortality and morbidity in the world. Despite ongoing efforts, current options for diagnosis and treatment are limited, and the underlying molecular mechanisms that lead to the manifestation of detrimental phenotypes in the heart remain largely elusive. The major goals of the HUPO Cardiovascular Initiative are to develop and apply cutting-edge proteomics and other omics technologies to map the dynamic cardiac and vascular proteomes, elucidate cardiovascular disease mechanisms, identify candidate therapeutic targets, and provide clinically useful diagnosis as well as risk prediction. 

Our Work

Emphasis is given to elucidating the complete cardiovascular proteome at single cell and proteoform resolution, and applying large-scale screening toward clinical diagnostics and prognosis of heart diseases. 

Publications:

• Cai W, Zhang J, de Lange WJ, Gregorich ZR, Karp H, Farrell ET, Mitchell SD, Tucholski T, Lin Z, Biermann M, McIlwain SJ, Ralphe JC, Kamp TJ, Ge Y. An Unbiased Proteomics Method to Assess the Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes. Circ Res. 2019 Nov 8;125(11):936-953. doi: 10.1161/CIRCRESAHA.119.315305. Epub 2019 Oct 1. PMID: 31573406; PMCID: PMC6852699.

• Herrington DM, Mao C, Parker SJ, Fu Z, Yu G, Chen L, Venkatraman V, Fu Y, Wang Y, Howard TD, Jun G, Zhao CF, Liu Y, Saylor G, Spivia WR, Athas GB, Troxclair D, Hixson JE, Vander Heide RS, Wang Y, Van Eyk JE. Proteomic Architecture of Human Coronary and Aortic Atherosclerosis. Circulation. 2018 Jun 19;137(25):2741-2756. doi: 10.1161/CIRCULATIONAHA.118.034365. PMID: 29915101; PMCID: PMC6011234.

• Lau E, Cao Q, Lam MPY, Wang J, Ng DCM, Bleakley BJ, Lee JM, Liem DA, Wang D, Hermjakob H, Ping P. Integrated omics dissection of proteome dynamics during cardiac remodeling. Nat Commun. 2018 Jan 9;9(1):120. doi: 10.1038/s41467-017-02467-3. PMID: 29317621; PMCID: PMC5760723.

• Lau E, Han Y, Williams DR, Thomas CT, Shrestha R, Wu JC, Lam MPY. Splice-Junction-Based Mapping of Alternative Isoforms in the Human Proteome. Cell Rep. 2019 Dec 10;29(11):3751-3765.e5. doi: 10.1016/j.celrep.2019.11.026. PMID: 31825849; PMCID: PMC6961840.

• Lee SH, Hadipour-Lakmehsari S, Murthy HR, Gibb N, Miyake T, Teng ACT, Cosme J, Yu JC, Moon M, Lim S, Wong V, Liu P, Billia F, Fernandez-Gonzalez R, Stagljar I, Sharma P, Kislinger T, Scott IC, Gramolini AO. REEP5 depletion causes sarco-endoplasmic reticulum vacuolization and cardiac functional defects. Nat Commun. 2020 Feb 19;11(1):965. doi: 10.1038/s41467-019-14143-9. PMID: 32075961; PMCID: PMC7031342.

• Li DK, Smith LE, Rookyard AW, Lingam SJ, Koay YC, McEwen HP, Twigg SM, Don AS, O'Sullivan JF, Cordwell SJ, White MY. Multi-omics of a pre-clinical model of diabetic cardiomyopathy reveals increased fatty acid supply impacts mitochondrial metabolic selectivity. J Mol Cell Cardiol. 2022 Mar;164:92-109. doi: 10.1016/j.yjmcc.2021.11.009. Epub 2021 Nov 24. PMID: 34826416.

• Martin TG, Myers VD, Dubey P, Dubey S, Perez E, Moravec CS, Willis MS, Feldman AM, Kirk JA. Cardiomyocyte contractile impairment in heart failure results from reduced BAG3-mediated sarcomeric protein turnover. Nat Commun. 2021 May 19;12(1):2942. doi: 10.1038/s41467-021-23272-z. PMID: 34011988; PMCID: PMC8134551.

• Papadaki M, Kampaengsri T, Barrick SK, Campbell SG, von Lewinski D, Rainer PP, Harris SP, Greenberg MJ, Kirk JA. Myofilament glycation in diabetes reduces contractility by inhibiting tropomyosin movement, is rescued by cMyBPC domains. J Mol Cell Cardiol. 2022 Jan;162:1-9. doi: 10.1016/j.yjmcc.2021.08.012. Epub 2021 Sep 3. PMID: 34487755; PMCID: PMC8766917.

• Wojtkiewicz M, Berg Luecke L, Castro C, Burkovetskaya M, Mesidor R, Gundry RL, Bottom-up proteomic analysis of human adult cardiac tissue and isolated cardiomyocytes. J Mol Cell Cardiol. 2022 Jan;162:20-31. doi: 10.1016/j.yjmcc.2021.08.008. PMID: 34437879