Yucheng Yao
University of California-Los Angeles, CA·Medicine & Clinical Research
Endothelial cells (ECs), the cells lining blood vessels, normally keep a stable identity. When they drift into the wrong identity, vessels can become tangled or hardened.
- Fields
Medicine & Clinical Research
Biology
Genetics
- Topics
arteriovenous malformations
cerebral AVM
hemorrhagic stroke
- Grants
- 3 known grants, through Apr 2030
What they work on
- Determine how loss of the receptor ALK1 raises MDM2 in artery endothelial cells, giving them lymphatic-like features that cause arteriovenous malformations, using endothelial ALK1-deficient mice.
- Assess MDM2's contribution to human hereditary hemorrhagic telangiectasia type 2, and test whether limiting MDM2 with an identified compound reduces AVMs in ALK1-deficient mice.
- Test whether a drug that blocks BIM, a cell-death-related protein, steers endothelial-derived bone-forming cells back to endothelial identity and reduces vascular calcification in diabetic mouse models.
- Test whether BIM gene deletion limits the shift of endothelial cells to bone-forming cells, and define how these cells push smooth muscle cells and fibroblasts toward bone formation, including in patients with diabetes.
- Determine how crosstalk between BMP and Notch signaling induces HDAC2, a histone-modifying enzyme, to shift brain endothelial cells toward mesenchymal-like cells that form cerebral AVMs.
- Evaluate HDAC2 induction in human cerebral AVMs, and test whether endothelial HDAC2 deletion or HDAC2 inhibition improves cerebral AVMs in mouse models.
More about the research
This research asks what pushes ECs into these harmful states and whether drugs or gene changes can push them back. Three projects address arteriovenous malformations (AVMs), abnormal direct connections between arteries and veins that can bleed, and vascular calcification, a bone-like hardening of arteries common in diabetes. All three use mouse genetic models alongside human tissue.
Why it matters
There is no medical treatment to prevent or shrink AVMs in HHT patients, and no effective therapy limits vascular calcification in diabetes. This work could identify drug targets, namely MDM2, BIM and HDAC2, for patients with HHT, brain AVMs that cause hemorrhagic stroke, and diabetes-related artery hardening that drives cardiovascular disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Beth Roman
University of Pittsburgh, PA·Biology
Determine why BMP9 and BMP10 are processed differently, using cell biology and biochemistry, and test in mouse models whether BMP10 made by hepatic stellate cells is required to prevent AVMs.
Edda Spiekerkoetter
Stanford University, CA·Medicine & Clinical Research
Build a mouse model of pulmonary arteriovenous malformations (PAVMs) by deleting HHT-causing genes (ENG, ALK1, SMAD4) in specific endothelial cell subgroups, and map PAVM origin using spatial transcriptomics and 3-D lung imaging.
Yujun Cai
Yale University, CT·Pharmacology
Investigate how PDE10A drives vascular smooth muscle cells exposed to high phosphate to turn into bone-like cells and calcify, using PDE10A knockdown and inhibition in cultured cells and PDE10A-deficient animals.
The school
University of California-Los Angeles: 84 labs on PI Pages, $1.9B a year on research, 803 research doctorates a year.
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