Discovering the Cure for an Incurable Disease

By Aastha Dubal, majoring in Nutrition Science and Research

October 25, 2021

The human body can be an overachiever when it comes to repairing itself. For the most part, it does a great job at fixing both internal and external injuries, but when they become a little too good at this job, the effects can be detrimental.

Dr. James Hagood, Professor of Pediatrics, Division of Pulmonology, UNC School of Medicine, Director, Program for Rare and Interstitial Lung Disease, Children’s Research Institute and Marsico Lung Institute. Image courtesy of Dr. Hagood.

In the lungs, this occurs in a condition called idiopathic pulmonary fibrosis (IPF) and the pathology of this disease may be better understood through an analogy. Imagine a handyman arrives to fix a hole in the wall. The handyman first comes and patches up the wall, solving the problem, yet he returns the next day and applies another layer of plaster. He does the same thing every day until the room is ultimately unusable ¹.

Dr. James Hagood from the UNC School of Medicine uses this analogy to describe IPF, a disease that affects more than 100,000 people in the United States ¹. Fibroblast cells in the lungs (the handymen) normally respond to lung injuries by becoming active and producing scar tissue (the plaster). The process occurs in the lungs fairly often because humans are constantly accumulating microinjuries by inhaling toxic substances, fighting infections, and developing inflammation ¹. In healthy lungs, fibroblasts come to the rescue, restore our lung’s function, and deactivate. However, in patients with IPF, fibroblasts are perpetually active and continuously produce scar tissue. In most cases, this leads to lung failure and death ¹.

Dr. Hagood’s interest in interstitial lung disease research extends to his early days as a physician. As a resident at Vanderbilt University, he cared for several premature infants who had received artificial surfactant, a relatively new therapy for underdeveloped lungs at the time. His firsthand experience of seeing new research in practice was fascinating for Dr. Hagood. This inspired him to begin his own lab and start searching for answers himself¹. He states, “Lung development and scarring and how they might be related to each other is the thing that got into my head and started waking me up at night.¹”

Dr. Hagood’s research lab discovered that a molecule called Thy-1 is responsible for regulating fibroblast activity ². By using a mouse model for IPF, he and his team were able to halt the progression of the disease and even reverse it by administering a solution of Thy-1 to the mice. The cell-surface molecule was able to deactivate the fibroblasts and stop them from overproducing scar tissue. Through further testing, Dr. Hagood found that Thy-1 is absent on the surface of fibroblasts in mice with IPF but present in mice with normal lung tissue ². The root cause of this difference in Thy-1 expression is yet unkown. Currently, the Hagood Lab is working with Dr. Ronit Freeman at UNC’s Dept. of Applied Physical Sciences to develop a molecule that mimics Thy-1 and can be used as a potential drug therapy ¹. This breakthrough discovery was the first step in developing a cure for a disease that has thus far been uncurable.

Seeing patients fighting pulmonary fibrosis continues to fuel Dr. Hagood’s drive for finding cures to rare lung diseases such as IPF1. He says, “Even if you are working on a disease that affects just a handful of people, to them, it’s really important. Everybody should have the same opportunity to be healthy and take advantage of what life has to offer.

Figure 1: Activated myofibroblasts in the lungs are shown in green. Muscle protein is shown in red. Image courtesy of Dr. Hagood.

References:

1.     Interview with Dr. James Hagood, MD. 9/8/21.

2.     Tan, C.; Jiang, M.; Wong, S.; Espinoza, C.; Kim, C.; Li, X.; Conners, E.; Hagood, J. JCI Insight. 2019. doi:10.1172/jci.insight.131152