Jay W. Heinecke, M.D.
Metabolism, Endocrinology and Nutrition
Professor of Medicine
Research in our laboratory focuses on the role of macrophages in the pathogenesis of atherosclerosis, diabetes and obesity. A central effort of the research group is the identification of mechanisms that mediate site-specific modification of proteins by activated phagocyte. There is also a strong interest in using tandem mass spectrometry to identify the shed and secreted proteome of macrophages. The research group employs a variety of techniques, including mass spectrometry, high-performance liquid chromatography and high resolution nuclear magnetic resonance spectroscopy, to identify and quantify proteins and oxidized biomolecules. Genetically engineered mice are used to establish the physiological importance of oxidative stress and macrophages in atherosclerosis and obesity. Another major effort centers on the application of proteomics techniques to translational studies of human cardiovascular disease.
Takeshita J, Byun J, Nhan TQ, Pritchard DK, Pennathur S, Schwartz SM, Chait A, Heinecke JW: Myeloperoxidase generates 5-chlorouracil in human atherosclerotic tissue: A potential pathway for somatic mutagenesis by macrophages. J Biol Chem 281:3096-104, 2006.
Shao B, Oda MN, Bergt C, Fu X, Green PS, Brot N, Oram JF, Heinecke JW: Myeloperoxidase impairs ABCA1-dependent cholesterol efflux through methionine oxidation and site-specific tyrosine chlorination of apolipoprotein A-I. J Biol Chem 281:9001-4, 2006.
Heinecke JW: Lipoprotein oxidation in cardiovascular disease: chief culprit or innocent bystander? J Exp Med 203:813-6, 2006.
Shao B, Oda MN, Oram JF, Heinecke JW: Myeloperoxidase: an inflammatory enzyme for generating dysfunctional HDL Curr Opin Cardiology 21::322-8, 2006.
Heinecke JW: Chemical knock-out of C-reactive protein. Nature Chem Biol 2:300-1, 2006.
Vaisar V, 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 X, 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 117:746-56, 2007.