Jay Heinecke, MD
Title:
Professor, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition
Email Address:
Background:
Dr. Heinecke earned his MD degree from Washington University in St. Louis in 1981 and then came to the UW for a residency in internal medicine. He was also a postdoctoral fellow in the Division of Metabolism, Endocrinology and Nutrition and then a senior fellow in the UW Department of Biochemistry from 1987 until 1990. He was a faculty member at Washington University in St. Louis from 1991 until 2002, when he was professor of medicine and professor of molecular biology and pharmacology there. In 2002, he returned to the UW to take his current position. He also directs the Mass Spectrometry Resource in the Department of Medicine and is an attending physician at UW Medical Center and a member of the Molecular and Cellular Biology Graduate Program. He holds the Karasinski Chair in Metabolic Research.
Dr. Heinecke has received numerous awards, including the American Heart Association's Jeffrey M. Hoeg Arteriosclerosis, Thrombosis and Vascular Wall Biology Award in 2001 and an Excellence in Mentoring Award from the Washington University Graduate Student Senate in 2002. He is a member of several editorial boards, including the Journal of Clinical Investigation, the Journal of Lipid Research and the Journal of Biological Chemistry.
Focus:
Dr. Heinecke's research focuses on understanding the role of macrophages and HDL in the pathogenesis of atherosclerosis, diabetes and obesity. A major effort is directed towards using proteomics and mice with genetically engineered proteins to understand macrophage activation.
Current studies include:
- Proteomics approaches to understand the cell biology of macrophages and dendritic cells –immune cells derived from circulating monocytes– that are implicated in the pathogenesis of inflammatory diseases;
- Use of animals with genetically engineered deficiencies in phagocyte oxidant generation and MMPs to understand the role of oxidants and proteases in the pathogenesis of cardiovascular disease;
- Human and animal studies exploring the links between the HDL proteome, insulin resistance, and susceptibility to cardiovascular disease.
Representative Publications:
Vaisar V., Pennathur S., Green P.S., Gharib S.A., Hoofnagle A.N., Knopp R.H., Brunzell J., Geary R., Chait A., Zhao X., Elkon K., Marcovina S., Ridker P., Oram J.F., Heinecke J.W.: Shotgun proteomics implicates protease inhibition and complement activation in the anti-inflammatory properties of HDL. J. Clin. Invest. 2007;117:746-56.
Oram J.F., Heinecke J.W.: When good cholesterol turns bad: the evolving saga of CETP inhibitors and clinical strategies to elevate high-density lipoprotein. Curr. Atheroscler. Rep. 2007;9:425-7.
Shao B., Heinecke J.W.: Using MS/MS to quantify site-specific chlorination and nitration of proteins: Model system studies with high density lipoprotein oxidized by myeloperoxidase. Meth. Enzymol. 2008;440:33-63.
Green P., Vaisar T.V., Pennathur S., Kulstad J.J., Moore A.B., Marcovina S., Brunzell J., Knopp R.H., Zhao X.Q., Heinecke J.W.: Combined statin and niacin therapy remodels the HDL proteome. Circulation. 2008;118:1259-67.
Heinecke J.W.: The HDL proteome: A marker—and perhaps mediator—of coronary artery disease. J. Lipid Res. 2009;50:S167-71.
Shao B., Cavigiolio G., Brot N., Oda M.N., Heinecke J.W.: Methionine oxidation impairs reverse cholesterol transport by apolipoprotein A-I. Proc. Natl. Acad. Sci. 2009;105:12224-9.
Vaisar T., Kassim S.Y., Gomez I.G., Green P.S., Hargarten S., Gough P.J., Parks W.C., Wilson C.L., Raines E.W., Heinecke J.W.: MMP-9 sheds the b2 integrin subunit (CD18) from macrophages. Mol. Cellular Proteomics. 2009;8:1044-60.
Shao B, Oda MN, Oram JF, Heinecke JW. Myeloperoxidase: an oxidative pathway for generating dysfunctional high-density lipoprotein. Chem Res Toxicol. 2010:15;23:447-54. PMID: 20043647; PMC2838938.
Shao B, Pennathur S, Pagani I, Oda MN, Witztum JL, Oram JF, Heinecke JW. Modifying apolipoprotein A-I by malondialdehyde, but not by an array of other reactive carbonyls, blocks cholesterol efflux by the ABCA1 pathway. J Biol Chem. 2010;285:18473-84. PMID: 20378541.
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;11:125-35. PMID: 20142100.
Current Collaborations:
Within the Diabetes and Obesity Center of Excellence and its Affiliated Members
Renee LeBoeuf, PhD
Karin Bornfeldt, PhD
Alan Chait, MD
Michael Schwartz, MD
Lab Members:
Andy Hoofnagle, MD, PhD
Jake Wimberger, MS
Angela Irwin, MS
Baohai Shao, PhD
Ilona Babenko
Lev Becker, PhD
Nathaline Pamir, PhD
Ning-Chun Liu, PhD
Phill Mayer, PhD
Tomas Vaisar, PhD
Zack Sagawa, MS