Welcome to the Bornfeldt Laboratory

Dedicated to understanding the cellular and molecular mechanisms of diabetes-accelerated cardiovascular disease.

The Bornfeldt laboratory is dedicated to understanding the cellular and molecular mechanisms of diabetes-accelerated cardiovascular disease, so that these complications can be effectively treated or prevented.
People with type 1 or type 2 diabetes have a greater risk of developing cardiovascular disease (myocardial infarction, stroke, and peripheral cardiovascular disease, which can with time lead to the necessity to amputate limbs) caused in large part by atherosclerosis. These complications can also develop earlier in life than in people without diabetes. Risk factors for cardiovascular disease associated with diabetes include sub-optimal metabolic control, increased inflammation, and lipid abnormalities, such as increased levels of triglycerides and changed levels of HDL (“the good cholesterol”).

Stages of atherosclerosis accelerated by diabetes. A cross-section of a normal artery (upper left) shows an open lumen for unobstructed blood flow. The normal artery consists of smooth muscle cells (red) and elastin filaments (black). A single layer of endothelial cells lines the lumen. Diabetes accelerates the formation of lesions of atherosclerosis in arteries. In early stage lesions (lower left), circulating immune cells (monocytes) have invaded the arterial wall and matured into macrophages. The smooth muscle cells have started to grow and move into the developing lesion. In advanced stages of atherosclerosis that develop over time (right) the lesions can be very large and complex. There are pockets of macrophages, smooth muscle cells, cholesterol accumulation in structures called cholesterol clefts, and necrotic cores (caused by dying macrophages). Poorly controlled diabetes causes these lesions to develop and progress at a faster pace. When the lumen is occluded by a sudden blood clot, a heart attack or stroke may occur, depending on the location of the occluded artery.
We also study blood samples from human subjects with diabetes to identify new biomarkers and mechanisms for cardiovascular disease risk in combination with mechanistic mouse models to identify new targets for prevention and treatment of cardiovascular complications of diabetes.

Our work is, or has been, funded by the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, the American Diabetes Association, the Juvenile Diabetes Research Foundation, and Novo Nordisk A/S.

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Current Laboratory Members

Karin Bornfeldt, PhD
Karin Bornfeldt, PhD

Principal Investigator, Edwin L. Bierman Professor of Medicine
Professor of Laboratory Medicine and Pathology

My career has been devoted to the discovery of cellular and molecular mechanisms of cardiovascular complications associated with diabetes. After completing my PhD on the effects of insulin and insulin-like growth factor 1 in vascular cells in Sweden, I was offered a position as a Postdoctoral Fellow in the laboratory of Dr. Russell Ross. During this time, I also interacted closely with Dr. Edwin Krebs, who was awarded the Nobel Prize in 1992, in studying signal transduction pathways in vascular cells. Work in my laboratory led to the development of a transgenic mouse model of type 1 diabetes-accelerated atherosclerosis, in which T cell-mediated destruction of the beta-cell can be induced at will by viral infection. By using this model, my group has shown that diabetes accelerates initiation of atherosclerotic lesions by stimulating macrophage accumulation within the vascular wall (Renard et al. J Clin Invest. 2004) and lesion intraplaque hemorrhage (Johansson et al. PNAS. 2008). More recently, my laboratory has been interested in the role of fatty acid-derived acyl-CoAs in atherosclerosis and inflammation (Kanter et al. PNAS. 2012), the effects of glucose in vascular cells (Nishizawa et al. Cell Rep. 2014; Wall et al. JCI Insight. 2018), and the effects of diabetes on triglycerides and HDL. I have had 23 pre- and postdoc trainees in my laboratory so far, and I am heavily involved in their training and future careers. I also frequently participate in minority student teaching. My administrative duties include serving as Associate Director for Research of the UW Medicine Diabetes Institute and as Deputy Director of the Diabetes Research Center (DRC) at the University of Washington for which I also direct a core facility (the Vector and Transgenic Mouse Core), serving as PI on a Program Project Grant and as Co-Director on a T32 training grant in Nutrition, Obesity and Atherosclerosis, chairing a large number of review panels, organizing scientific meetings, and organizing a weekly research training conference. For specific examples of the types of projects we work on, please see the descriptions of student research below.

Farah Kramer, BS
Farah Kramer, BS

Research Scientist II, Lab Manager

Research Interests: Developing and maintaining mouse models of diabetes-accelerated atherosclerosis (Bornfeldt et al. Am J Pathol. 2018).

Shelley Barnhart, BS
Shelley Barnhart, BS

Research Scientist II

Research Interests: The role of the enzyme acyl-CoA synthetase 1 in myeloid cells in diabetes and other autoinflammatory diseases, and analysis of atherosclerotic lesion morphology (Basu et al. Circ Res. 2018).

Jenny Kanter, PhD
Jenny Kanter, PhD

Research Assistant Professor

Research Interests: Effects of diabetes and insulin resistance on monocytes and macrophages in mouse models of diabetes-accelerated atherosclerosis, and mechanisms of diabetes-accelerated atherosclerosis (Kanter et al. 2018)

Brian Van Yserloo, BS
Brian Van Yserloo, BS

Research Scientist II

Research Interests: Research Scientist Research Interests: CRISPR/Cas9-mediated genome editing in cells and mice (Shimizu-Albergine et al. Proc Natl Acad Sci USA. 2016).

Jingjing Tang, PhD
Jingjing Tang, PhD

Research Scientist

Research Interests: The role of the protease ADAM17 in inflammation, macrophage proliferation, and atherosclerosis.

Luz Wigzell, BS
Luz Wigzell, BS

Research Scientist

Research Interests: Histology and atherosclerosis lesion morphology.

Masami Shimizu-Albergine, PhD
Masami Shimizu-Albergine, PhD

Research Scientist

Research Interests: Cholesterol sensing through SCAP (Shimizu-Albergine et al. Proc Natl Acad Sci USA. 2016) and effects of triglyceride-lowering on atherosclerosis in the presence of diabetes.

Vishal Kothari, PhD
Vishal Kothari, PhD

Postdoctoral Fellow

Research Interests:Analysis of HDL function and dysfunction in the setting of diabetes (He et al. Arterioscler Thromb Vasc Biol. 2018).

Lab Alumni

Hye Seung Jung, MD
Hye Seung Jung, MD

Visiting Scientist from Seoul National University Hospital, Korea

Research Interests: The role of the acyl-CoA synthetase 3 in human endothelial cells.

Yunosuke Matsuura, MD, PhD
Yunosuke Matsuura, MD, PhD

Postdoctoral Fellow

Research Interests: How diabetes affects the metabolism of macrophages.

Eyal Kedar, MD
Eyal Kedar, MD

Rheumatology Fellow

Research Interests: Effects of lupus on monocyte and macrophage activation and atherosclerosis.

Tomohiro Nishizawa, PhD
Tomohiro Nishizawa, PhD

Visiting Scientist from Daiichi-Sankyo Co., Japan

Research Interests: Effects of glucose in myeloid cells and atherosclerosis. Recent publications: Nishizawa & Bornfeldt 2012; Nishizawa et al. 2014

Sara Vallerie, PhD
Sara Vallerie, PhD

Postdoctoral Fellow

Research Interests: Downstream effects of acyl-CoA synthetase 1 deficiency in macrophages as they relate to atherosclerosis.

Valerie Wall, BS
Valerie Wall, BS

Graduate Student (Pathology Graduate Program

Research Interests: Acyl-CoA thioesterases in macrophage biology and atherosclerosis, glucose effects in smooth muscle cells.

Contact Us

UW Medicine Diabetes Institute
750 Republican Street, Box 358062
Seattle, WA 98109

 

Karin Bornfeldt: (206) 543-1681
Lab Main Line: (206) 616-3551
Fax: (206) 543-3567

Careers
To inquire about Postdoctoral and Graduate Student Openings click on: bornf@u.washington.edu