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Vaisar_T_102[1]

Tomas Vaisar, Ph.D.

Metabolism, Endocrinology and Nutrition

Research Associate Professor of Medicine


Focus

Dr. Vaisar's research focuses on examining the role of inflammation in the development and progression of cardiovascular disease. Specifically, his research looks at the role lipoproteins in the development of cardiovascular disease. Dr. Vaisar applies state of the art mass spectrometric methods to characterization of HDL and multiplexed MRM based quantitative analysis of all proteins in HDL.


Summary

Tomas Vaisar received his PhD at the Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences in Prague, Czech Republic in 1992. In 2002 he joined the laboratory of Dr. Jay W. Heinecke at the University of Washington, Seattle.  He is currently a Research Associate Professor at the Diabetes and Obesity Center of Excellence at the University of Washington.


Research Interest

Current projects focus on:

• HDL as a mediator and carrier of biomarkers of cardiovascular disease. This project focuses on development and application of quantitative proteomic methods to discovery of biomarkers of cardiovascular disease.  Unlike whole plasma, HDL is a simple proteome of up to 100 proteins which is in the causal pathway of cardiovascular disease. Quantitative assessment of HDL proteome can therefore provide biomarkers for disease diagnosis as well as markers of therapeutic intervention efficacy.

• Role of inflammation in the pathogenesis of cardiovascular disease with particular focus on the role of HDL and its interactions with cells in the artherosclerotic lesions (macrophages, endothelial cells and smooth muscle cells). Inflammation is one of the hallmarks of atherosclerosis and is associated with major changes in the HDL protein composition, activation of cells in the arterial wall, and increased production of proteases in the atherosclerotic lesions. We are addressing questions of how the changes in HDL composition affect its anti-atherogenic properties and what is the role of proteolysis in the progression of atherosclerosis.

To address these questions his lab is using state of the art proteomic techniques and has developed targeted quantitative methods for HDL proteome analysis and an unbiased proteomics approach for identification of physiological proteolytic substrates.


Publications

Page ST, Krauss RM, Gross C, Ishida B, Heinecke JW, Tang C, Amory JK, Schaefer PM, Cox CJ, Kane J, Purnell JQ, Weinstein RL, Vaisar T. Impact of Mifepristone, a Glucocorticoid/Progesterone Antagonist, on HDL Cholesterol, HDL Particle Concentration, and HDL Function. J Clin Endocrinol Metab. 2012 Mar 7. [Epub ahead of print] PubMed PMID: 22399518.

Vaisar T. Proteomics Investigations of HDL: Challenges and Promise. Curr Vasc  Pharmacol. 2012 Feb 20. [Epub ahead of print] PubMed PMID: 22339300.

Hoofnagle AN, Becker JO, Oda MN, Cavigiolio G, Mayer P, Vaisar T. Multiple-Reaction Monitoring-Mass Spectrometric Assays Can Accurately Measure the Relative Protein Abundance in Complex Mixtures. Clin Chem. 2012 Feb 3. [Epub ahead of print] PubMed PMID: 22307200.

Cheung MC, Vaisar T, Han X, Heinecke JW, Albers JJ. Phospholipid transfer protein in human plasma associates with proteins linked to immunity and inflammation. Biochemistry. 2010 Aug 31;49(34):7314-22. PubMed PMID: 20666409; PubMed Central PMCID: PMC2930196.

Thorp E, Vaisar T, Subramanian M, Mautner L, Blobel C, Tabas I. Shedding of the Mer tyrosine kinase receptor is mediated by ADAM17 protein through a pathway  involving reactive oxygen species, protein kinase Cδ, and p38 mitogen-activated protein kinase (MAPK). J Biol Chem. 2011 Sep 23;286(38):33335-44. Epub 2011 Aug 2. PubMed PMID: 21828049; PubMed Central PMCID: PMC3190938.

Chiba T, Chang MY, Wang S, Wight TN, McMillen TS, Oram JF, Vaisar T, Heinecke  JW, De Beer FC, De Beer MC, Chait A. Serum amyloid A facilitates the binding of high-density lipoprotein from mice injected with lipopolysaccharide to vascular proteoglycans. Arterioscler Thromb Vasc Biol. 2011 Jun;31(6):1326-32. Epub 2011 Apr 7. PubMed PMID: 21474830; PubMed Central PMCID: PMC3129975.

Suzuki M, Pritchard DK, Becker L, Hoofnagle AN, Tanimura N, Bammler TK, Beyer  RP, Bumgarner R, Vaisar T, de Beer MC, de Beer FC, Miyake K, Oram JF, Heinecke JW. High-density lipoprotein suppresses the type I interferon response, a family  of potent antiviral immunoregulators, in macrophages challenged with lipopolysaccharide. Circulation. 2010 Nov 9;122(19):1919-27. Epub 2010 Oct 25. PubMed PMID: 20974999; PubMed Central PMCID: PMC2988582.

Hoofnagle AN, Vaisar T, Mitra P, Chait A. HDL lipids and insulin resistance. Curr Diab Rep. 2010 Feb;10(1):78-86. Review. PubMed PMID: 20425071.

Heinecke NL, Pratt BS, Vaisar T, Becker L. PepC: proteomics software for identifying differentially expressed proteins based on spectral counting. Bioinformatics. 2010 Jun 15;26(12):1574-5. Epub 2010 Apr 22. PubMed PMID: 20413636; PubMed Central PMCID: PMC2881356.

Vaisar T, Mayer P, Nilsson E, Zhao XQ, Knopp R, Prazen BJ. HDL in humans with cardiovascular disease exhibits a proteomic signature. Clin Chim Acta. 2010 Jul 4;411(13-14):972-9. Epub 2010 Mar 20. PubMed PMID: 20307520; PubMed Central PMCID: PMC2862883.

Becker L, Gharib SA, Irwin AD, Wijsman E, Vaisar T, Oram JF, Heinecke JW. A macrophage sterol-responsive network linked to atherogenesis. Cell Metab. 2010 Feb 3;11(2):125-35. PubMed PMID: 20142100; PubMed Central PMCID: PMC2893224.

Wool GD, Vaisar T, Reardon CA, Getz GS. An apoA-I mimetic peptide containing  a proline residue has greater in vivo HDL binding and anti-inflammatory ability than the 4F peptide. J Lipid Res. 2009 Sep;50(9):1889-900. Epub 2009 May 11. PubMed PMID: 19433476; PubMed Central PMCID: PMC2724789.

Chiba T, Han CY, Vaisar T, Shimokado K, Kargi A, Chen MH, Wang S, McDonald TO, O’Brien KD, Heinecke JW, Chait A. Serum amyloid A3 does not contribute to circulating SAA levels. J Lipid Res. 2009 Jul;50(7):1353-62. Epub 2009 Mar 12. PubMed PMID: 19286646; PubMed Central PMCID: PMC2694334.

Vaisar T. Thematic review series: proteomics. Proteomic analysis of lipid-protein complexes. J Lipid Res. 2009 May;50(5):781-6. Epub 2009 Feb 19. Review. PubMed PMID: 19229074; PubMed Central PMCID: PMC2666164.

Vaisar T, Kassim SY, Gomez IG, Green PS, Hargarten S, Gough PJ, Parks WC, Wilson CL, Raines EW, Heinecke JW. MMP-9 sheds the beta2 integrin subunit (CD18)  from macrophages. Mol Cell Proteomics. 2009 May;8(5):1044-60. Epub 2008 Dec 30. PubMed PMID: 19116209; PubMed Central PMCID: PMC2689762.

1Green PS, Vaisar T, Pennathur S, Kulstad JJ, Moore AB, Marcovina S, Brunzell  J, Knopp RH, Zhao XQ, Heinecke JW. Combined statin and niacin therapy remodels the high-density lipoprotein proteome. Circulation. 2008 Sep 16;118(12):1259-67.  Epub 2008 Sep 2. PubMed PMID: 18765395; PubMed Central PMCID: PMC2735443.

Fu X, Gharib SA, Green PS, Aitken ML, Frazer DA, Park DR, Vaisar T, Heinecke  JW. Spectral index for assessment of differential protein expression in shotgun proteomics. J Proteome Res. 2008 Mar;7(3):845-54. Epub 2008 Jan 17. PubMed PMID:  18198819.

Vaisar T, Shao B, Green PS, Oda MN, Oram JF, Heinecke JW. Myeloperoxidase and inflammatory proteins: pathways for generating dysfunctional high-density lipoprotein in humans. Curr Atheroscler Rep. 2007 Nov;9(5):417-24. PubMed PMID: 18001626.

Vaisar T, Pennathur S, Green PS, Gharib SA, Hoofnagle AN, Cheung MC, Byun J,  Vuletic S, Kassim S, Singh P, Chea H, Knopp RH, Brunzell J, Geary R, Chait A, Zhao XQ, Elkon K, Marcovina S, Ridker P, Oram JF, Heinecke JW. Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory  properties of HDL. J Clin Invest. 2007 Mar;117(3):746-56. PubMed PMID: 17332893;  PubMed Central PMCID: PMC1804352.

Blacken GR, Volný M, Vaisar T, Sadílek M, Turecek F. In situ enrichment of phosphopeptides on MALDI plates functionalized by reactive landing of zirconium(IV)-n-propoxide ions. Anal Chem. 2007 Jul 15;79(14):5449-56. Epub 2007  Jun 15. PubMed PMID: 17569507; PubMed Central PMCID: PMC2576294.