Rewriting the Rules of Lung Repair: Inside Penn Vet’s Quest to Prevent Lasting Lung Damage
Why do some lungs bounce back after severe infection while others are left with permanent, life-altering damage? That’s the question driving the work of Andrew Vaughan, PhD, associate professor of biomedical sciences at the University of Pennsylvania School of Veterinary Medicine.
A molecular and cellular biologist, Vaughan is focused on understanding how lungs heal—and why the repair process sometimes goes wrong. His research aims to uncover the biological signals that determine whether a patient fully recovers from respiratory injury or develops chronic inflammation and scarring that can impair breathing for life.
“The lung sits in the middle ground of tissue repair,” Vaughan explains. “It’s much more regenerative than the brain or the heart, but much less regenerative than the liver.”
This delicate balance makes the lung especially vulnerable after major insults like viral infections. Some patients, including those recovering from COVID-19, regain normal lung function. Others experience long-term complications caused by fibrosis, where damaged tissue is replaced with stiff scar tissue that limits the lungs’ ability to expand and exchange oxygen.
Vaughan’s lab is working to understand what separates these two outcomes.
At the center of their research is the idea that recovery can be derailed by cellular miscommunication. When lung tissue is injured, cells must coordinate a complex repair response. But in some cases, that process becomes dysregulated, leading to chronic inflammation and progressive scarring.
A key area of focus is how damaged lung epithelial cells, the cells lining the airways, interact with fibroblasts, the cells responsible for forming connective tissue. Under normal conditions, fibroblasts help repair injured areas. But when signals go wrong, they can drive excessive scar formation.
Vaughan points to the work of graduate student Nick Holcomb as a major step forward in understanding this process. Holcomb investigated how viral injury to epithelial cells affects nearby fibroblasts during recovery.
His findings suggest that after infection, epithelial cells can become dysfunctional and begin releasing signals that push fibroblasts into overdrive. These activated fibroblasts then recruit additional immune cells, fueling ongoing inflammation. Over time, this creates a feedback loop that promotes fibrosis rather than healing.
The result: lungs that never fully recover.
By mapping these cellular interactions, Vaughan’s team hopes to identify targets for therapies that could interrupt this harmful cycle. The long-term goal is not just to treat lung damage, but to prevent it—or even reverse it—by guiding the body back toward healthy regeneration.
This work comes at a critical time, as researchers continue to confront the long-term respiratory effects of viral infections and other lung injuries. Despite the promise of these discoveries, Vaughan and his colleagues are navigating a challenging research landscape shaped by shrinking federal funding for biomedical science.
Even so, the mission remains clear: understand why some lungs heal and others scar, and use that knowledge to change outcomes for both human and animal patients.
As regenerative medicine continues to evolve, research like Vaughan’s is helping rewrite the rules of recovery, bringing science one step closer to therapies that can restore damaged lungs and improve quality of life long after the initial injury has passed.
Original article here: https://penntoday.upenn.edu/news/penn-vet-rewriting-rules-lung-repair
