Preventing vessel narrowing after bypass with an epigenetic drug and local nanoparticle coating
Epigenetic targeting and nanoplatform-enabled local drug delivery - a two-pronged approach to stenosis prevention after vascular surgery
This project tries to stop blood vessel narrowing after bypass or other vascular surgery by blocking a gene regulator called DOT1L and delivering its inhibitor locally with a nanoparticle 'paint'.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Virginia NIH-funded |
| Lab location | 1 site (Charlottesville, United States) |
| Project ID | NIH-11239084 on NIH RePORTER |
What this research studies
Researchers found that DOT1L, an epigenetic regulator, drives smooth muscle cells to change in ways that narrow grafted vessels. In mice and rat models, blocking DOT1L reduced this harmful change, and the team created a prototype called Epi^NanoPaint to deliver the DOT1L inhibitor Pinometostat directly at the surgery site. The grant work focuses on refining the drug targeting and the local sustained-delivery nanoparticle so the approach is safe and long-lasting for open vascular reconstructions. If these steps go well, the team aims to move the approach closer to testing in people.
Who could benefit from this research
Good fit: People scheduled for open vascular reconstruction such as vein bypass grafting who are at risk of post-surgical vessel narrowing would be the ideal candidates for this approach.
Not a fit: Patients with artery narrowing caused by non–smooth-muscle mechanisms, certain clotting disorders, or those not undergoing surgical grafting may not benefit from this treatment approach.
Why it matters
Potential benefit: If successful, this approach could lower graft failure and reduce the need for repeat procedures after vascular surgery.
How similar studies have performed: Preclinical animal studies and smooth muscle cell–specific knockout models showed DOT1L inhibition reduced neointimal hyperplasia, but the combined epigenetic targeting plus nanoparticle delivery has not yet been tested in humans.
Where this research is happening
Charlottesville, United States
- University of Virginia — Charlottesville, United States (Active)
Researchers
- Principal investigator: Guo, Lianwang — University of Virginia
- Study coordinator: Guo, Lianwang
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.