Christopher Waters, PhD, of UTHSC Receives $1.7 Million Grant to Study Mechanisms Related to Ventilator-Induced Lung Injury

Dr. Christopher Waters has received a $1.7 million grant to examine the therapies associated with ventilator-induced lung injury specifically looking at the protein ASK1, in the hopes of reducing lung injury during treatment. (Photo by Thurman Hobson, UTHSC)

The University of Tennessee Health Science Center’s Christopher Waters, PhD, professor and interim chair of the Department of Physiology in the College of Medicine, has received a $1.7 million award from the National Institutes of Health for his project titled “ASK1 and Ventilator-Induced Lung Injury.” The study will examine the therapies associated with ventilator-induced lung injury (VILI), specifically looking at the protein ASK1, in the hopes of reducing lung injury during treatment.

Acute Respiratory Distress Syndrome (ARDS) is a devastating disease that is commonly caused by infection or injury to the lungs. According to the American Lung Association, there are approximately 200,000 cases of ARDS each year in the United States and very few therapeutic options are currently available. The treatment of these patients with supplemental oxygen and mechanical ventilation is necessary to sustain them. However, research has shown that while both mechanical ventilation and hyperoxia can contribute to injury independently, the combination of these two factors can accelerate and cause more extensive lung injury to patients than either condition alone.

“We have been studying the mechanisms behind how this additional injury occurs,” Dr. Waters said. “The goal is to reduce the injury that is caused by either the mechanical ventilation, the oxygen, and the combination of the two. We want to understand how the injury occurs and how we can minimize it.”

This project developed from earlier studies done in collaboration with Scott Sinclair, MD, associate professor in the Department of Medicine in the College of Medicine and director of the Intensive Care Unit at Regional One Health, along with Patrudu S. Makena, PhD, a former postdoctoral fellow at UTHSC. Those studies showed that a particular protein, apoptosis signal regulating kinase-1 (ASK1), can be activated by both hyperoxia and mechanical stretching of the lungs in mice. The ASK1 protein has long been known to be involved in several processes in the body causing inflammation and cell death. Dr. Waters’ team is focusing on this particular protein and what pathways are being activated downstream from it in the hopes that lung injury can be reduced by blocking ASK1-related pathways.

“We’re trying to understand which of these pathways are being activated in this combined hyperoxia and mechanical ventilation environment, and whether or not blocking ASK1 might reduce further injury,” Dr. Waters said. “We know that ARDS patients require oxygen and mechanical ventilation in order for them to survive. However, with a mortality rate of almost 40 percent in the United States, we want to understand the therapy and its contribution to mortality.”

Dr. Waters is hopeful that this four-year study will help to identify which pathways are being activated and the mechanisms leading to additional injury in the hopes of minimizing it and thus improving ARDS patient survival.