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.
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.
Which lineage(s) of leukocyte you like to work with the most: Macrophages because they use metabolism in so many interesting ways
What is your most favorite lab equipment: Confocal microscope
What is your least favorite lab equipment: Messy freezers
If you were not a scientist, what other profession could you see yourself doing: Science is IT for me - has been since I was a little girl
What other language(s) do you speak, or have learned in school: Swedish (and un petit peu French)
What do you like to do to relax: Anything nature-related!
What character do you like to dress up to be this Halloween: Mary Anning
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).
Which lineage(s) of leukocyte you like to work with the most: macrophages
What is your most favorite lab equipment: dissecting microscope
What is your least favorite lab equipment: anything that constantly beeps.
If you were not a scientist, what other profession could you see yourself doing: a baker
What other language(s) do you speak, or have learned in school: Malay
What do you like to do to relax: camping and traveling with family
What character do you like to dress up to be this Halloween: It is a well-kept secret, one will only know on October 31st, it could be a character from a fairytale, a musical, a cartoon, a movie or I could even be a bride!
Jenny Kanter, PhD
Research Assistant Professor
Research Interests: My research focus is primarily on how lipids alter cells involved in diabetic kidney disease and diabetes-accelerated atherosclerosis. I have always been interested in how myeloid cells respond to lipids and how they contribute to complications of diabetes. Although I still have numerous collaborative projects together with the Bornfeldt lab, I now have my own lab
Which lineage(s) of cells do you like to work with the most: Any primary cell, but I do like macrophages.
What is your most favorite lab equipment: I love pretty images, so a good microscope is my favorite.
What is your least favorite lab equipment: This is not a piece of equipment, but any type of labeling. It is so important but oh so boring!
If you were not a scientist, what other profession could you see yourself doing: Some sort of teacher perhaps.
What other language(s) do you speak or have learned in school: I am originally from Sweden so I do speak Swedish.
What do you like to do to relax: Running is my go-to de-stressor.
What character do you like to dress up to be this Halloween: Whatever I can throw together last minute.
Ahreum Khang, MD
Visiting Scientist
Research Interests: diabetes, diabetic complications, macrophage, mitochondria
Which lineage(s) of leukocyte you like to work with the most: Macrophages
What is your most favorite lab equipment: Seahorse machine
What is your least favorite lab equipment: None
If you were not a scientist, what other profession could you see yourself doing: Hmm, teacher?
What other language(s) do you speak, or have learned in school: Korean
What do you like to do to relax: Rolling around in bed
What character do you like to dress up to be this Halloween: My daughter wants to be a cat, so I will be a cat’s mom!
Jingjing Tang, PhD
Research Scientist
Research Interests: The role of the protease ADAM17 in inflammation, macrophage proliferation, and atherosclerosis.
Which lineage(s) of leukocyte you like to work with the most: macrophages, they are doing everything; neutrophils, they can easily burst
What is your most favorite lab equipment: The Revco -80oC chest freezer. It has been working for 3 PIs over a span of 35 years, and is still going strong!
What is your least favorite lab equipment: Hemavet. It has an unpredictable temperament
If you were not a scientist, what other profession could you see yourself doing: A historian
What other language(s) do you speak, or have learned in school: Mandarin. Attempted to learn Japanese and German
What do you like to do to relax: Play with my pup and read
What character do you like to dress up to be this Halloween: A character in Star Wars
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.
Which lineage(s) of leukocyte you like to work with the most: Macrophages
What is your most favorite lab equipment: Fluorescent microscopy (you can collect beautiful color images if you have good antibodies)
What is your least favorite lab equipment: Transferring proteins to a membrane for Western blots (I often have undesired lousy marks on it)
If you were not a scientist, what other profession could you see yourself doing: Some kind of service provider for the public/community
What other language(s) do you speak, or have learned in school: Japanese
What do you like to do to relax: Ferry rides between Bainbridge Island and Seattle (only summer time), sitting with my dog and reading a book
What character do you like to dress up to be this Halloween: A naval aviator
Luz Wigzell, BS
Research Scientist
Research Interests:Histology and atherosclerosis lesion morphology.
Which lineage(s) of leukocyte you like to work with the most: NA
What is your most favorite lab equipment: Microtome
What is your least favorite lab equipment: Cryostat
If you were not a scientist, what other profession could you see yourself doing: photographer
What other language(s) do you speak, or have learned in school: Spanish
What do you like to do to relax: Gardening
What character do you like to dress up to be this Halloween: A cat
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).
Graduate Students
Cheng-Chieh (Steven) Hsu
PhD Candidate Research Interest: My research interests involve cell interactions and responses in disease settings, especially diabetes and vascular complications as a result of diabetes. I focus on the role of apolipoprotein C3-containing triglyceride-rich lipoproteins and macrophage inflammasome pathways in diabetes-associated atherosclerosis.
Which lineage(s) of leukocyte you like to work with the most: Monocytes and macrophages
What is your most favorite lab equipment: Flow cytometer
What is your least favorite lab equipment: Hemavet
If you were not a scientist, what other profession could you see yourself doing: Food or restaurant critic. Traveling around and sampling different foods sounds nice.
What other language(s) do you speak, or have learned in school: Mandarin
What do you like to do to relax: Walk around the park, read, or play video games.
What character do you like to dress up to be this Halloween: Sheet ghost
Dr. Karin Bornfeldt, awarded the George Lyman Duff Memorial Lectureship at the American Heart Association’s Scientific Sessions
Karin Bornfeldt, Edwin L. Bierman Professor of Medicine, was awarded the George Lyman Duff Memorial Lectureship at the American Heart Association’s Scientific Sessions. The lectureship was established in 1956 by the Society for the Study of Arteriosclerosis in memory of Dr. Duff, a founding member and past president of the society. Past award recipients from the UW include Edwin Bierman (1991), Russell Ross (1980) and John Glomset (1979).
Dr. Karin Bornfeldt, has received a new Program Project Grant from the National Heart, Lung, and Blood Institute. . This grant, totaling $12 million over the next five years, includes four projects and three core units at the University of Washington, New York University and Washington University.
Dr. Karin Bornfeldt, Edwin L. Bierman Professor of Medicine, and professor of Laboratory Medicine and Pathology, has received a new Program Project Grant from the National Heart, Lung, and Blood Institute. The primary focus of the new Triglycerides, Diabetes and Cardiovascular Disease Program Project is to investigate whether diabetes causes changes in remnants of triglyceride-rich lipoproteins, and whether these changes contribute to the increased cardiovascular disease risk associated with diabetes. This grant, totaling $12 million over the next five years, includes four projects and three core units at the University of Washington, New York University and Washington University. DOM project leaders are Jay Heinecke and Karin Bornfeldt and core directors are Karin Bornfeldt, Tomas Vaisar and Jenny Kanter. Baohai Shao (Metabolism, Endocrinology and Nutrition) is a Co-Investigator on the program.
Jingjing presenting at ATVB in May 2022
Dr. Karin Bornfeldt, is senior author in Circulation Research.
Karin Bornfeldt, PhD, is senior author of “Diabetes Suppresses Glucose Uptake and Glycolysis in Macrophages” in Circulation Research. DOM co-authors are Masami Shimizu-Albergine, Shelley Barnhart, Farah Kramer, Cheng-Chieh Hsu, Vishal Kothari, Jingjing Tang, Sina Gharib, Jenny Kanter, and Baohai Shao.
Dr. Karin Bornfeldt, co-authored a review in Cell Metabolism
Karin Bornfeldt, PhD, co-authored a review in Cell Metabolism, “Cardiovascular disease in diabetes, beyond glucose.”
Dr. Karin Bornfeldt, is Senior Author in Circulation
Dr. Karin Bornfeldt, has been appointed as holder of the Edwin L. Bierman Professorship in Metabolism, Endocrinology and Nutrition
Dr. Karin Bornfeldt, PhD, has been appointed as holder of the Edwin L. Bierman Professorship in Metabolism, Endocrinology and Nutrition.
Lab Alumni
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).
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
Postdoctoral Fellow
Research Interests: How diabetes affects the metabolism of macrophages.
Eyal Kedar, MD
Rheumatology Fellow
Research Interests: Effects of lupus on monocyte and macrophage activation and atherosclerosis.
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).
Which lineage(s) of leukocyte you like to work with the most: Tissue macrophages: Very important contributors in diverse physiological and pathological functions
What is your most favorite lab equipment: Microscope, RT-qPCR machine, flow cytometer (I keep myself challenged)
What is your least favorite lab equipment: Cell counter
If you were not a scientist, what other profession could you see yourself doing: Businessman or farmer
What other language(s) do you speak, or have learned in school: Hindi, Gujarati
What do you like to do to relax: Play with my son
What character do you like to dress up to be this Halloween: Avengers
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
Postdoctoral Fellow
Research Interests: Downstream effects of acyl-CoA synthetase 1 deficiency in macrophages as they relate to atherosclerosis.
Valerie Wall, PhD
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
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.
