Blood clots in the lungs affect up to 900,000 people in the United States every year and are the third-leading cause of cardiovascular-related deaths. But what if gene editing, made possible through ultra-small nanoparticles, could effectively treat clot-induced tissue damage?
For USC School of Medicine scientist Colin Evans, the question is no longer hypothetical.
Evans, an assistant professor in the Department of Cell Biology and Anatomy, focuses on improving outcomes for inflammatory vascular disease. He uses nanoparticle-mediated gene editing technology to treat lung tissue damage in laboratory models and in ex vivo human lung tissue. Specifically, the lab looks at damage in the endothelial cells that line the lung’s blood vessels.
“The technology for increasing or decreasing the expression of certain signaling proteins or enzymes in endothelial cells of patients with inflammatory lung injury has not yet come to fruition, but we think it will,” says Evans, who joined the School of Medicine Columbia faculty two years ago. “When that happens, our lab will be well positioned in knowing which signaling pathways can help improve outcomes.”
Some of the nanoparticles used in these types of gene editing technologies, he notes, are already approved for clinical use in humans.
Evans’ gene editing research to inhibit tissue damage stems from his longstanding focus on the fundamental mechanisms of thrombosis — the formation of blood clots. One of his recent papers, published in Circulation Research, assesses the impact of different levels of lung thrombosis that occur in inflammatory lung injury. It turns out that a mild level of thrombosis in the lungs can be beneficial for patients affected by acute respiratory distress syndrome or COVID-19.
“The technology for increasing or decreasing the expression of certain signaling proteins or enzymes in endothelial cells of patients with inflammatory lung injury has not yet come to fruition, but we think it will. When that happens, our lab will be well positioned in knowing which signaling pathways can help improve outcomes.”
“If you have no thrombosis at all or a severe level of thrombosis, we observed an increased level of vascular tissue injury in the lungs,” Evans says. “But if you have what we refer to as an intermediate or mild level of thrombosis, that can actually reduce the levels of lung injury.”
The innocuous level of thrombosis stimulates certain enzymes to produce lipids that promote survival of the lung’s endothelial cells in close proximity to the blood clots. Evans’ lab is focused on a particular enzyme called arachidonate 15 lipoxygenase, which plays an important role in regulating inflammation and producing lipids that improve endothelial cell survival in the lung.
“What we’re trying to do is build a foundation of evidence that this enzyme consistently improves outcomes with regards to endothelial cell injury or lung injury,” Evans says. “The nanoparticle-mediated gene editing we’re using can increase the levels of beneficial proteins in as little as one day and reduce the levels of genes and proteins that cause tissue injury in three or four days.”
Another vein of Evans’ research is aimed at repurposing certain drugs to enhance thrombosis resolution. For example, patients with chronic kidney disease are prescribed with drugs that increase the level of red blood cells, but these medications also increase the activity of a protein that helps break down clots in the veins.
“We think if we can deliver those drugs to the endothelial cells in and around the thrombus, we can promote an increase in blood flow through the resolving thrombus and veins,” Evans says. “So, we're aiming to achieve cell-specific drug delivery, ideally of FDA-approved drugs that are already known to be safe in humans but can be repurposed to help different conditions.”
Evans has two active research grants from the American Heart Association as well as research project funding through the South Carolina IDeA Networks of Biomedical Research Excellence, which is intended to foster success in achieving further NIH grant funding.
He earned his bachelor’s in sport and exercise sciences at the University of Birmingham
in England, where he developed an interest in vascular remodeling as a response to
exercise. His interest in thrombosis came into focus while earning a Ph.D. from King’s
College London. Before joining USC, Evans completed post-doctoral training at the
University of Cambridge, and he was on the research faculty at Northwestern University.
