Welcome to the Bornfeldt Laboratory
Dedicated to understanding the cellular and molecular mechanisms of
diabetes-accelerated cardiovascular disease
General Research Description
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 lead to the necessity to amputate limbs) caused by atherosclerosis. These complications also develop earlier in life than in people without diabetes. Risk factors for cardiovascular disease associated with diabetes include sub-optimal metabolic control and lipid abnormalities, such as increased levels of triglycerides and decreased HDL.
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 (right) that develop over time the lesions can be very large and almost occlude the lumen. There are pockets of macrophages, smooth muscle cells, cholesterol accumulation in structures called cholesterol clefts, and necrotic cores (caused by dying macrophages). Diabetes causes these lesions to develop and progress at a faster pace. When the lumen is occluded, a heart attack or stroke may occur, depending on the location of the occluded artery.
We have demonstrated, using a mouse model of type 1 diabetes-accelerated atherosclerosis (Renard et al. 2004; Johansson et al. 2008) that diabetes stimulates both initiation of lesions of atherosclerosis and progression to advanced lesions, and that this is in large part due to an increased inflammatory state of monocytes and macrophages (Kanter et al. 2012). We have recently shown that by blocking an enzyme (acyl-CoA synthetase 1) involved in fatty acid utilization by these cells, it is possible to prevent development of early lesions of diabetes in diabetic mice, without affecting lesions in non-diabetic mice (Kanter et al. 2012). This suggests that there are specific targets for treatment or prevention of diabetes-accelerated atherosclerosis. Our current research is focused on identifying additional targets.
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.
Jenny Kanter’s research highlighted in Nature
Jenny Kanter’s research highlighted in Circulation Research
Current and Recent Members of the Bornfeldt Laboratory
Karin Bornfeldt, PhD, Principal Investigator
Professor of Medicine and PathologyMy 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.I established my laboratory in at the University of Washington in 1997. 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 macrophages and endothelial cells, and the role of S100A9 in insulin resistance and atherosclerosis in mice (Averill et al. Circulation 2011).I currently hold two R01s, an R01-sized project on a Program Project Grant, and a grant from Novo Nordisk A/S in the area of cardiovascular complications of diabetes. I collaborate with many groups in the US and Europe. I have had 19 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 of the Diabetes and Obesity Center of Excellence and as Deputy Director of the Diabetes Research Center (DRC) at the University of Washington for which I also direct a core facility (the Viral 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, including as a member of the NHLBI Program Project Grant Parent Committee (HLBP), 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. Click here for publication list..
Michelle Averill, PhD
Acting Assistant Professor, Nutritional Sciences Program andDepartment of Environmental and Occupational Health Sciences
Shelley Barnhart, BS
Research Scientist 2
Research interests: Molecular biology, macrophage function, S100 proteins.
Oscar Gonzalez, MD
Cardiology Fellow, University of Washington
Research interests: The role of acyl-CoA synthetase 1 in endothelial cells. Dr. Gonzalez has moved on to the clinical part of his fellowship.Recent publications: Li, Gonzalez et al. 2013
Jenny Kanter, PhD
Senior Postdoctoral Fellow
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.
Eyal Kedar, MD
Research interest: Effects of lupus on monocyte and macrophage activation and atherosclerosis.
Farah Kramer, BS
Research Scientist 2, Lab Manager
Research Interests: Developing and maintaining transgenic mouse models of diabetes-accelerated atherosclerosis, immunohistological evaluation of atherosclerotic lesions.
Tomohiro Nishizawa, PhD
Visiting Scientist from Daiichi-Sankyo Co., Japan 2009-2011
Research Interests: Effects of glucose in macrophages and atherosclerosis.
Recent publications: Nishizawa & Bornfeldt 2012
Xia (Clare) Shen, PhD
Research Scientist 2
Research Interests: Effects induced in human endothelial cells by increased acyl-CoA synthesis.
Recent publications: Li et al. 2013
Ricky Rualo, BS
Assistant Research Scientist
Research Interests: Mouse colony management, genotyping and various projects in the lab.
Katya Rubinow, MD
Acting Instructor, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition
Research Interests: Regulation and function of acyl-CoA synthetase 1 in macrophages. Dr. Rubinow is currently developing her independent research program.
Sara Vallerie, PhD
Research Interests: Downstream effects of acyl-CoA synthetase 1 deficiency in macrophages as they relate to atherosclerosis.
Valerie Wall, BS
Graduate Student (Pathology Graduate Program)
Research interests: Acyl-CoA thioesterases in macrophage biology.
Diabetes and Obesity Center of Excellence
Department of Pathology
University of Washington School of Medicine
South Lake Union Campus
850 Republican Street
Seattle, WA 98109-8055
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Fax: (206) 543-3567
Karin Bornfeldt: (206) 543-1681
Lab: (206) 616-3551
Michelle Averill: firstname.lastname@example.org
Karin Bornfeldt: email@example.com
Shelley Barnhart: firstname.lastname@example.org
Jenny Kanter: email@example.com
Eyal Kedar: firstname.lastname@example.org
Sara Valerie: email@example.com
Valerie Wall: firstname.lastname@example.org
To inquire about Postdoctoral and Graduate Student Openings click on: email@example.com