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Cardiovascular Initiative

Cardiovascular initiative

Cardiovascular diseases are the most prevalent class of diseases in the world; more individuals die from heart diseases than any other illness. Despite current and past efforts, diagnosis and treatment options are limited. The underlying molecular mechanisms that lead to the onset and progression of detrimental phenotypes in the heart remain largely elusive. The major goals of the HUPO Cardiovascular Initiative include the development and utilization of cutting-edge proteomics technologies and beyond 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. Emphasis is given to promoting the development and adoption of quantitative protein assays targeting relevant cardiovascular proteins, elucidating the complete cardiovascular proteome at single cell and proteoform resolution, and application of large-scale screening towards clinical diagnostics and prognosis of heart diseases.

Current lines of work:

Continual development of computational algorithms to prioritize popular proteins for expedited quantitative proteomics assay development.
Quantitation of cardiovascular proteins using integrated antibody and targeted MRM approaches.
Characterization of proteins relevant to the onset, progression and reversal of cardiovascular diseases including cardiac hypertrophy, aortic aneurysm, vasculopathies, and others.
Deciphering the impact of posttranslational modifications (e.g., citrullination, phosphorylation, etc.) in signalling and protein regulation under cardiovascular physiology and pathophysiology.

Links:

2015 Cardiovascular Initiative Workshop Program

Highlights of the Biology and Disease-driven Human Proteome Project, 2015-2016

Papers:

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

Lin Z, Wei L, Cai W, Zhu Y, Tucholski T, Mitchell SD, Guo W, Ford SP, Diffee GM, Ge Y. Simultaneous Quantification of Protein Expression and Modifications by Top-down Targeted Proteomics: A Case of Sarcomeric Subproteome. Mol Cell Proteomics. 2018 Dec 27. pii: mcp.TIR118.001086. doi: 10.1074/mcp.TIR118.001086. [Epub ahead of print]

Stachowski MJ, Holewinski RJ, Grote E, Venkatraman V, Van Eyk JE, Kirk JA. Phospho-Proteomic Analysis of Cardiac Dyssynchrony and Resynchronization Therapy. Proteomics. 2018 Oct;18(19):e1800079. doi: 10.1002/pmic.201800079. Epub 2018 Aug 30.

Wang J, Choi H, Chung NC, Cao Q, Ng DCM, Mirza B, Scruggs SB, Wang D, Garlid AO, Ping P. Integrated Dissection of Cysteine Oxidative Post-translational Modification Proteome During Cardiac Hypertrophy. J Proteome Res. 2018 Aug 31. Sp

DeLeon-Pennell KY, Iyer RP, Ma Y, Yabluchanskiy A, Zamilpa R, Chiao YA, Cannon PL, Kaplan A, Cates CA, Flynn ER, Halade GV, de Castro Brás LE, Lindsey ML. The Mouse Heart Attack Research Tool 1.0 database. Am J Physiol Heart Circ Physiol. 2018 Sep 1;315(3):H522-H530. Epub 2018 May 18.

Waas M, Weerasekera R, Kropp EM, Romero-Tejeda M, Poon EN, Boheler KR, Burridge PW, Gundry RL. Are These Cardiomyocytes? Protocol Development Reveals Impact of Sample Preparation on the Accuracy of Identifying Cardiomyocytes by Flow Cytometry.Stem Cell Reports. 2019 Jan 8. In press.

Wang SB, Venkatraman V, Crowgey EL, Liu T, Fu Z, Holewinski R, Ranek M, Kass DA, O'Rourke B, Van Eyk JE. Protein S-Nitrosylation Controls Glycogen Synthase Kinase 3β Function Independent of Its Phosphorylation State. Circ Res. 2018 May 25;122(11):1517-153

Papadaki M, Holewinski RJ, Previs SB, Martin TG, Stachowski MJ, Li A, Blair CA, Moravec CS, Van Eyk JE, Campbell KS, Warshaw DM, Kirk JA. Diabetes with heart failure increases methylglyoxal modifications in the sarcomere, which inhibit function. JCI Insight. 2018 Oct 18;3(20). pii: 121264. [Epub ahead of print] PMID: 30333300.

Lindsey ML, Jung M, Hall ME, DeLeon-Pennell KY. Proteomic analysis of the cardiac extracellular matrix: clinical research applications. Expert Rev Proteomics. 2018 Feb;15(2):105-112.

Joshi A, Mayr M. In Aptamers They Trust: The Caveats of the SOMAscan Biomarker Discovery Platform from SomaLogic. Circulation. 2018 Nov 27;138(22):2482-2485. Epub 2018 Nov 26

Suna G, Wojakowski W, Lynch M, Barallobre-Barreiro J, Yin X, Mayr U, Baig F, Lu R, Fava M, Hayward R, Molenaar C, White SJ, Roleder T, Milewski KP, Gasior P, Buszman PP, Buszman P, Jahangiri M, Shanahan CM, Hill J, Mayr M. Extracellular Matrix Proteomics Reveals Interplay of Aggrecan and Aggrecanases in Vascular Remodeling of Stented Coronary Arteries. Circulation. 2018 Jan 9;137(2):166-183. Epub 2017 Oct 13.

Lam MPY, Ge Y. Harnessing the Power of Proteomics to Assess Drug Safety and Guide Clinical Trials. Circulation. 2018 Mar 6;137(10):1011-1014.

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. 2018 Jan 9;9(1):120. doi: 10.1038/s41467-017-02467-3.

Ranek MJ, Kokkonen-Simon KM, Chen A, Dunkerly-Eyring BL, Vera MP, Oeing CU, Patel CH, Nakamura T, Zhu G, Bedja D, Sasaki M, Holewinski RJ, Van Eyk JE, Powell JD, Lee DIk, Kass DA. PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress. Nature volume 566, pages264–269 (2019)

Parker SJ, Venkatraman V, Van Eyk JE. Effect of peptide assay library size and composition in targeted data-independent acquisition-MS analyses. Proteomics. 2016 Aug;16(15-16):2221-37.

Lam MP, Venkatraman V, Cao Q, Wang D, Dincer TU, Lau E, Su AI, Xing Y, Ge J, Ping P, Van Eyk JE. Prioritizing Proteomics Assay Development for Clinical Translation. J Am Coll Cardiol. 2015 Jul 14;66(2):202-4.

Lam MP, Venkatraman V, Xing Y, Lau E, Cao Q, Ng DC, Su AI, Ge J, Van Eyk JE, Ping P. Data-Driven Approach To Determine Popular Proteins for Targeted Proteomics Translation of Six Organ Systems. J Proteome Res. 2016 Jul 19. [Epub ahead of print]

Semba RD, Lam M, Sun K, Zhang P, Schaumberg DA, Ferrucci L, Ping P, Van Eyk JE. Priorities and trends in the study of proteins in eye research, 1924-2014. Proteomics Clin Appl. 2015 Dec;9(11-12):1105-22. doi: 10.1002/prca.201500006.

Fert-Bober J, Giles JT, Holewinski RJ, Kirk JA, Uhrigshardt H, Crowgey EL, Andrade F, Bingham CO 3rd, Park JK, Halushka MK, Kass DA, Bathon JM, Van Eyk JE. Citrullination of myofilament proteins in heart failure. Cardiovasc Res. 2015 Nov 1;108(2):232-42.