Beth Roman
University of Pittsburgh, PA·Biology
Normally, blood flows from arteries into veins through tiny capillaries. In hereditary hemorrhagic telangiectasia (HHT), a genetic disease affecting at least 1 in 5,000 people, some arteries connect straight to veins.
- Fields
Biology
Biochemistry
Medicine & Clinical Research
- Topics
hereditary hemorrhagic telangiectasia
arteriovenous malformations
bone morphogenetic proteins
- Grants
- 1 known grant, through May 2029
What they work on
- 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.
- Solve the structures that drive pairing of BMP9 with pro-BMP10 and limit cutting of pro-BMP10, using X-ray crystallography and single-particle cryogenic electron microscopy.
- Measure the activity of pro-BMP10-containing ALK1 signals in human endothelial cells, zebrafish and mice, testing the need for the endoglin receptor, protein cutting and blood flow shear stress.
More about the research
These faulty connections, called arteriovenous malformations (AVMs), can lead to anemia, stroke or heart failure. HHT arises when a signal carried in the blood fails to reach the endothelial cells that line blood vessels. The signal comes from the plasma proteins BMP9 and BMP10. They bind the receptors endoglin (ENG) and activin receptor-like kinase 1 (ALK1), and mutations in these receptors cause HHT. The team has shown that BMP10 is the only ALK1 signal needed to prevent AVMs in zebrafish and mice.
Why it matters
People with hereditary hemorrhagic telangiectasia currently face blood vessel malformations that can cause anemia, stroke or heart failure. Defining where the key blood-borne BMP10 signal comes from, how it is built and how it becomes active could guide the design of safe, stable, targeted protein drugs that prevent arteriovenous malformations in HHT.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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.
Yucheng Yao
University of California-Los Angeles, CA·Medicine & Clinical Research
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.
Clara Kielkopf
University of Rochester, NY·Biochemistry
Compare how recurrent U2AF2 mutations found in neurodevelopmental disorders and in cancers affect RNA binding and splicing, using structural methods and pre-mRNA splicing assays in human cells.
The school
University of Pittsburgh: 83 labs on PI Pages, $1.5B a year on research, 403 research doctorates a year.
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