Karin Bornfeldt
University of Washington, WA·Medicine & Clinical Research
People with type 1 or type 2 diabetes develop heart attacks and strokes earlier and more often than people without diabetes. Lowering blood sugar and LDL cholesterol does not remove this extra risk.
- Fields
Medicine & Clinical Research
Physiology
Microbiology & Immunology
- Topics
atherosclerosis
cardiovascular disease
type 1 diabetes
- Grants
- 5 known grants, through Feb 2033
What they work on
- Test whether higher plasma APOC3, a protein that controls triglyceride-rich particles, tracks with build-up of a mid-sized lipoprotein particle and worsening insulin resistance and arterial stiffness in youth with type 1 or type 2 diabetes followed over time.
- Compare the structure and function of triglyceride-rich lipoprotein (TRL) and remnant particle subtypes to find which ones promote artery plaque and blood vessel inflammation.
- Determine whether a faulty liver secretion pathway involving sortilin 1 and APOB100 explains excess APOC3 release and faster atherosclerosis, using diabetic mouse models and cell systems.
- Test whether TREM2, a lipid-sensing receptor on myeloid immune cells, protects liver cells from fat overload and APOC3-rich lipoprotein output, using type 2 diabetes mice with altered TREM2 shedding.
- Map how silencing APOC3 in the liver changes the cells inside artery plaques, using CITE-seq single-cell profiling and studies of isolated smooth muscle and endothelial cells.
- Test whether blood levels of soluble TREM2 predict heart attacks and strokes in people with type 2 diabetes, and whether this link involves APOC3.
- Find out why T cells from people with type 1 diabetes stick to and enter tissues more readily, using single-cell T-cell receptor sequencing and CITE-seq of blood cells and adhesion tests on human coronary artery cells.
- Track the build-up of CD4+ and CD8+ T-cell clones in type 1 diabetes artery plaques and kidney lesions from the CaRe-T1D biobank, using T-cell receptor sequencing and spatial proteomics.
More about the research
These grants ask what else drives it. Much of the work follows triglyceride-rich lipoproteins (TRLs), the fat-carrying particles in blood, and their partly broken-down leftovers, called remnant lipoprotein particles (RLPs). A second line looks at immune T cells in damaged arteries and kidneys. The work spans young patients, human tissue biobanks, mouse models and cultured cells.
Why it matters
Heart disease is the leading cause of death in type 1 diabetes and a major threat in type 2 diabetes, even when cholesterol is controlled. This work could give doctors new blood measures, such as APOC3 levels and lipoprotein particle types, for predicting cardiovascular risk in youth and adults with diabetes. It could also point to new prevention targets. APOC3-silencing therapies are nearing clinical trials, and these studies could support including people with type 2 diabetes in those trials.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Bo Wang
University of Illinois Urbana-Champaign, IL·Physiology
Examine how SEC16B, a scaffold protein on the endoplasmic reticulum, regulates the formation of lipid droplets (fat-storage bodies) in liver cells, using cell-culture and in vivo experiments.
Chiara Giannarelli
New York University, NY·Medicine & Clinical Research
Determine how cytotoxic γδ T cells contribute to atherosclerosis progression in type 2 diabetes, and whether the transcription factor ZEB2 drives their harmful functions, using mouse models and human plaque data.
Han Tan
University of California-Irvine, CA·Neuroscience·Early-career
Test whether BNC2 neurons, leptin-sensing cells in the hypothalamic arcuate nucleus, control the function of glucose-regulating organs through direct nerve connections.
The school
University of Washington: 81 labs on PI Pages, $1.7B a year on research, 694 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.