Daniel Greif
Yale University, CT·Medicine & Clinical Research
Smooth muscle cells (SMCs) form the muscular layer of artery walls. They keep blood vessels strong, but in many vascular diseases they multiply too much, end up in the wrong places, or change behavior in harmful ways.
- Fields
Medicine & Clinical Research
Biology
Genetics
- Topics
vascular smooth muscle cells
atherosclerosis
pulmonary hypertension
- Grants
- 3 known grants, through Apr 2028
What they work on
- Test whether brief reprogramming with the OSKM pluripotency factors resets aged smooth muscle cells to a younger epigenetic age while keeping their identity, using SMC-specific DNA methylation clocks in cells and mice.
- Determine whether transient OSKM reprogramming reduces arterial stiffness and atherosclerotic plaque buildup in aged mice, using vascular function assays, disease models and single-cell RNA sequencing.
- Identify how loss of elastin lowers the epigenetic enzymes DNMT1 and HDAC1 in human and mouse smooth muscle cells, using genome-wide epigenetic and gene expression profiling and human tissue samples.
- Test whether elastin deficiency switches on JAG1–NOTCH3 signaling through chromatin changes, and whether blocking histone acetyltransferases reduces aortic narrowing in mouse models of supravalvular aortic stenosis.
- Find and characterize smooth muscle progenitor cells in the aorta and lung arterioles, tracing their origins and their role in forming the vessel's muscle layer in mouse models.
- Uncover how PDGF-B and KLF4 drive single progenitors to expand in pulmonary hypertension and atherosclerosis, and how bone marrow-derived cells such as macrophages control their recruitment into plaques.
More about the research
This narrows or stiffens arteries. Heart and blood vessel disease is the leading cause of death worldwide. A central question across these projects is what controls SMC growth, identity and aging, and whether those controls can be targeted to treat disease. The projects cover a rare inherited artery narrowing, the progenitor cells that supply new SMCs in common diseases such as atherosclerosis and pulmonary hypertension, and how aging changes SMCs.
Why it matters
Supravalvular aortic stenosis can lead to heart failure and sudden death, and surgery is its only treatment. Identifying Notch and epigenetic enzymes as drivers could point to the first drug-based options for affected children, including those with Williams-Beuren syndrome. Understanding SMC progenitors and SMC aging may also suggest new treatment strategies for pulmonary hypertension, atherosclerosis and age-related arterial stiffening, which affect large numbers of older adults.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Robert Wirka
University of North Carolina at Chapel Hill, NC·Genetics
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.
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.
Zhen Yue Jiang
Boston University, MA·Physiology
Test whether neutrophil elastase (NE) drives vascular leakage, inflammation and fibrosis by activating PAR2 and ENaC signaling in vascular endothelial and smooth muscle cells, using cell culture and mouse studies.
The school
Yale University: 73 labs on PI Pages, $1.5B a year on research, 438 research doctorates a year.
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