Our Research: Faculty/Research Laboratories

Jay Heinecke, MD

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

Email Address: heinecke@u.washington.edu

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

Jay Heinecke, MC

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.

Focus:

The major focus of research in the Heinecke laboratory is to understand the role of HDL and macrophages in the pathogenesis of atherosclerosis, diabetes and other inflammatory diseases. Our efforts are directed towards identifying specific proteins that play key roles in cholesterol metabolism and macrophage inflammation in vivo.

Current studies include:

  • Investigation of the pathways that promote cholesterol efflux from macrophages, which is of central importance in the cardioprotective effects of HDL.
  • Translational studies to determine if altered HDL protein composition, macrophage sterol efflux, and inhibition of macrophage inflammation associate with CAD and diabetic status.
  • Human and animal studies exploring the links between the HDL proteome, insulin resistance, and susceptibility to cardiovascular disease.

Representative Publications:

Vaisar T., 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.

Green P., Vaisar T., 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.

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.

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.

Shao B, Heinecke JW. Impact of HDL oxidation by the myeloperoxidase system on sterol efflux by the ABCA1 pathway. J Proteomics. 2011 Oct 19;74(11):2289-99.

Becker L, Liu NC, Averill MM, Yuan W, Pamir N, Peng Y, Irwin AD, Fu X, Bornfeldt KE, Heinecke JW. Unique proteomic signatures distinguish macrophages and dendritic cells. PLoS One. 2012;7(3):e33297.

Shao B, Pennathur S, Heinecke JW. Myeloperoxidase targets apolipoprotein A-I, the major high density lipoprotein protein, for site-specific oxidation in human atherosclerotic lesions. J Biol Chem. 2012 Feb 24;287(9):6375-86.

Heinecke JW. The not-so-simple HDL story: A new era for quantifying HDL and cardiovascular risk? Nat Med. 2012 Sep 7;18(9):1346-7.

  • Shao B., Oda M.N., Bergt C., Fu X., Green P.S., Brot N., Oram J.F., Heinecke J.W.: Myeloperoxidase impairs ABCA1-dependent cholesterol efflux through methionine oxidation and site-specific tyrosine chlorination of apolipoprotein A-I. J. Biol. Chem. 2006;281:9001-4.

    Heinecke J.W.: Chemical knock-out of C-reactive protein. Nature Chem. Biol. 2006; 2:300-1, 2006.

    Vaisar T., Pennathur S., Green P.S., Gharib S.A., Hoofnagle A.N., Cheung M.C., Byun J., uletic S., Chait A., Zhao X.Q., 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 HDL oxidized by myeloperoxidase. Meth. Enzymol. 2008;440:33-63.

    Johansson F., Kramer F., Barnhart S., Kanter J.E., Vaisar T., Merrill R.D., Geng L., Oka K., Chan L., Chait A., Heinecke J.W., Bornfeldt K.E.: Type 1 diabetes promotes disruption of advanced atherosclerotic lesions in LDL receptor-deficient mice. Proc. Natl. Acad. Sci. 2008;105:2082-7.

    Kirk E.A., Sagawa Z.K., McDonald T.O., O’Brien K.D., Heinecke J.W.: MCP-1 deficiency fails to restrain macrophage infiltration into adipose tissue. Diabetes. 2008;57:1254-61.

    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. 2008;105:12224-9.

Current Collaborations:

Within the Diabetes and Obesity Center of Excellence and its Affiliated Members
Renee LeBoeuf, PhD
Karin Bornfeldt, PhD
Alan Chait, MD

Lab Members:

Jake Wimberger, MS
Angela Irwin, MS
Baohai Shao, PhD
Graziella Ronsein, PhD
Josh McBee, PhD
Katie Thomas, MS
Jeff Monette, PhD
Ilona Babenko, MS
Nathalie Pamir, PhD
Ning-Chun Liu, PhD
Yi He, PhD
Patrick Hutchins, PhD
Amy Wang
Phill Mayer, PhD
Zack Sagawa, MS