Robert Wirka
University of North Carolina at Chapel Hill, NC·Genetics
Atherosclerosis, the buildup of plaque in artery walls, drives coronary artery disease (CAD), the most common form of heart disease. Smooth muscle cells (SMCs) in the artery wall play a key role.
- Fields
Genetics
Medicine & Clinical Research
Biology
- Topics
atherosclerosis
coronary artery disease
smooth muscle cells
- Grants
- 1 known grant, through Nov 2028
What they work on
- Track individual smooth muscle cells as they multiply and choose fates during atherosclerosis, using a barcoding mouse model compatible with single-cell RNA sequencing, with and without Twist1 knockout.
- Test whether extra Twist1 in smooth muscle cells, mimicking the human risk allele, is enough to worsen atherosclerosis, using a myc-tagged Twist1 overexpression mouse model.
- Map genome-wide Twist1 DNA binding in smooth muscle cells in living mice to identify the genes this transcription factor directly controls during atherosclerosis.
- Identify the cellular pathways and transcription factors that act on the causal genetic variant at the 7p22.1 locus to regulate TWIST1 expression.
More about the research
During disease, a small number of them multiply heavily, change their identity and move into the plaque. This process is called phenotypic modulation. This project asks how a human risk gene, TWIST1, steers this process and raises the risk for several vascular diseases.
Why it matters
Coronary artery disease, stroke, peripheral artery disease and Moyamoya disease share a genetic risk region that acts through TWIST1. By explaining how common genetic changes raise TWIST1 levels and push artery smooth muscle cells toward disease, this work could reveal new targets for treating vascular disease. It will also produce a detailed map of smooth muscle cell behavior in atherosclerosis for other researchers.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Daniel Li
Stanford University, CA·Genetics·Early-career
Determine how losing ZEB1, a transcription factor linked to coronary artery disease risk, changes gene activity, epigenetic state and plaque features in smooth muscle–derived cells, using a Zeb1 knockout mouse model of atherosclerosis.
Clint Miller
University of Virginia, VA·Genetics
Determine how FHL5, a helper protein that tunes gene activity, causes vascular dysfunction through the actin cytoskeleton, the extracellular matrix and vessel constriction. The work will use human vascular cells and arteries studied ex vivo.
Joseph Miano
Augusta University, GA·Physiology
Define the coronary artery disease that develops in mice lacking Lmod1 only in vascular smooth muscle cells, using mouse genetics, spatial gene-activity profiling and immuno-electron microscopy of artery tissue.
The school
University of North Carolina at Chapel Hill: 72 labs on PI Pages, $1.6B a year on research, 523 research doctorates a year.
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