Our Research: Faculty/Research Laboratories

Tomas Vaisar, PhD

Research Associate Professor, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition

Email Address: tvaisar@u.washington.edu

Division of Metabolism, Endocrinology and Nutrition Website:  http://depts.washington.edu/metab/

Tomas Vaisar, PhD

Background:

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 and is currently a Research Assistant Professor at the Diabetes and Obesity Center of Excellence at the University of Washington.

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.

Current projects focus on:

• HDL as a 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.

Representative Publications:

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. 49:7314-7322, 2010. PMCID: PMC2930196.

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. 411:972-979, 2010. PMCID: PMC2862883.

Vaisar T. Thematic review series: proteomics. Proteomic analysis of lipid-protein complexes. J Lipid Res. 50:781-786, 2009. PMCID: PMC2666164.

Vaisar T, Kassim SY, Gomez IG, Green PS, Hargarten SA, Gough PJ, Parks WC, Wilson CL, Raines EW, Heinecke JW.  MMP-9 sheds the beta 2 integrin subunit (CD18) from macrophages.  Mol Cell Proteomics. 8:1044-1060, 2009.  PMCID:  PMC2689762.

Green 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. 118:1259-1267, 2008.  PMID: 18765395.

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. 7:845-854, 2008.  PMID: 18198819.

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 anti-inflammatory properties of HDL. J Clin Invest. 117:746-756, 2007.  PMID: 17332893.

  • Hoofnagle AN, Vaisar T, Mitra P, Chait A. HDL lipids and insulin resistance. Curr Diab Rep.10:78-86, 2010. Review.

    Heinecke NL, Pratt BS, Vaisar T, Becker L. PepC: proteomics software for identifying differentially expressed proteins based on spectral counting. Bioinformatics. 26:1574-1575, 2010. 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. 411:972-979, 2010. 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. 11:125-135, 2010. 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. 50:1889-1900, 2009. PMCID: PMC2724789.

    Gharib SA, Vaisar T, Aitken ML, Park DR, Heinecke JW, Fu X. Mapping the lung proteome in cystic fibrosis. J Proteome Res. 8:3020-3028, 2009. PMID: 19354268.

    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. 50:1353-1362, 2009. PMCID: PMC2694334.

    Vaisar T. Thematic review series: proteomics. Proteomic analysis of lipid-protein complexes. J Lipid Res. 50:781-786, 2009. Review. PMCID: PMC2666164.

    Vaisar T, Kassim SY, Gomez IG, Green PS, Hargarten SA, Gough PJ, Parks WC, Wilson CL, Raines EW, Heinecke JW:  MMP-9 sheds the beta 2 integrin subunit (CD18) from macrophages.  Mol Cell Proteomics. 8:1044-1060, 2009.  PMCID:  PMC2689762.

    Chang DW, Hayashi S, Gharib SA, Vaisar T, King ST, Tsuchiya M, Ruzinski JT, Park DR, Matute-Bello G, Wurfel MM, Bumgarner R, Heinecke JW, Martin TR.  Proteomic and computational analysis of bronchoalveolar proteins during the course of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 178:701-709, 2008.

    Green 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. 118:1259-1267, 2008.  PMID: 18765395.

    Xiao C, Watanabe T, Zhang Y, Trigatti B, Szeto L, Connelly PW, Marcovina S, Vaisar T, Heinecke JW, Lewis GF.  Enhanced cellular uptake of remnant high-density lipoprotein particles: a mechanism for high-density lipoprotein lowering in insulin resistance and hypertriglyceridemia. Circ Res. 103:159-166, 2008.

    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 shotgunproteomics. J Proteome Res. 7:845-854, 2008.

    Johansson F, Kramer F, Barnhart S, Kanter JE, Vaisar T, Merrill RD, Geng L, Oka K, Chan L, Chait A, Heinecke JW, Bornfeldt KE.  Type 1 diabetes promotes disruption of advanced atherosclerotic lesions in LDL receptor-deficient mice. Proc Natl Acad Sci USA. 105:2082-2087, 2008.

    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. 9:417-424, 2007.

    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. 79:5449-5456, 2007.

    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. 117:746-756, 2007.

    Shao B, Oda MN, Vaisar T, Oram JF, Heinecke JW.  Pathways for oxidation of high-density lipoprotein in human cardiovascular disease. Curr Opin Mol Ther. 8:198-205, 2006.

    Vaisar T, Heinecke JW, Seymour JL, Turecek F.  Copper-mediated intra-ligand oxygen transfer in gas-phase complexes with 3-nitrotyrosine.  J Mass Spectrom. 40:608-614, 2005.

    Woltjer RL, Nghiem W, Maezawa I, Milatovic D, Vaisar T, Montine KS, Montine TJ.  Role of glutathione in intracellular amyloid-alpha precursor protein/carboxy-terminal fragment aggregation and associated cytotoxicity. J Neurochem. 93:1047-1056, 2005.

Current Collaborations:

Within the Diabetes and Obesity Center of Excellence and its Affiliated Members
Jay Heinecke, MD
John Albers, PhD
Marian Cheung, PhD
Alan Chait, MD
William Parks, PhD

Outside the Diabetes and Obesity Center of Excellence
Elaine Raines, University of Washington
Kevin O’Brien, MD, University of Washington
Jonathan Purnell, MD, Oregon Health & Science University
Frank Turecek, PhD, University of Washington
Clem Furlong, PhD, University of Washington
Gary Lewis, FRCPC, MD, University of Toronto
Godfrey Getz, MD, University of Chicago
Frederick C. de Beer, MD, University of Kentucky
Olivier Meihlac, PhD, INSERM, Paris, France
John Kane, MD, PhD, UCSF
Bryan Prazen, PhD, Insilicos Inc.

Lab Members:

Ilona Babenko, MS