Lian-Wang Guo, PhD, a professor in the Department of Surgery, Division of Surgical Sciences, and Craig Kent, MD, a professor in the Department of Surgery and the chief executive officer of UVA Health and executive vice president for health affairs at the University of Virginia, were awarded a R01 grant for $2.8 million from the NIH to study the epigenetic “writer” DOT1L, an enzyme that marks histone proteins with methyl groups, in vascular stenotic disease.
Each year, over a million Americans receive open vascular reconstructions to restore blood flow to vital organs, such as bypass vein grafting on the heart to avoid heart failure. Unfortunately, the grafts fail at high rates, and there are no FDA-approved methods to prevent graft failure.
The investigators seek to tackle this problem using a two-pronged approach. They will determine the potential of DOT1L as a therapeutic target for treating graft stenosis or narrowing. Meanwhile, by collaborating with Shaoqin Gong, PhD, a multiple principal investigator at University of Wisconsin-Madison, they will develop an epiNanopaint strategy to deliver a DOT1L-inhibiting drug locally and sustainably by “painting” bioadhesive nanoparticles on vein grafts. This straight-forward method could be broadly applicable to other open vascular reconstructions including vascular access for renal dialysis.
Drs. Ki Ho Park, Bowen Wang, and Chengli Shen are co-investigators. Collaborators include Drs. Jianjie Ma, Amy Webb, Gary Owens, Nick Tsihlis, Melina Kibbe, Keith Ozaki (Harvard), and Colleen Brophy (Vanderbilt).
Filed Under: Research