UTHSC secures $1.5 million for lung-healing research

Dr. Christopher Waters, Professor and Vice Chair in the Department of Physiology at the University of Tennessee Health Science Center (UTHSC), will use a four-year, $1.5 million grant to study the repair process associated with various lung injuries. The grant comes from the National Heart, Lung, and Blood Institute, a subsidiary of the National Institutes of Health.
 
"In one of our recent studies, we found that this particular receptor, CXCR4, was important in the healing of lung epithelial cells following injury," says Waters, who for more than 20 years has been interested in how the lungs heal following injury. "Based upon this new finding and our earlier work on the biochemical signaling pathways involved in this process, we developed the grant proposal that was funded."
 
Patients with severe lung injury, including from infections and exposure to toxic substances, can develop a disease called Acute Respiratory Distress Syndrome (ARDS), one of the most frequent causes of admission into the intensive care unit. A major feature of ARDS is injury to the epithelial cells that line the respiratory tract and that normally protect the lungs from harmful substances in the inhaled air.
 
"ARDS is a devastating disease with very high mortality and limited treatment options," says Waters. "The mechanisms of repair following injury are still not well understood, and this project from NIH will allow us to examine a new pathway that has not previously been studied in the lungs."
 
Patients with ARDS are currently treated with supplemental oxygen and mechanical ventilation, but unfortunately many patients do not survive. While the treatment is essential for survival, mechanical ventilation itself can contribute to additional lung injury and may affect the repair processes. It was recently discovered that a particular substance called CXCL12 is released by injured lung cells, and that CXCL12 is important for the repair of the lungs. 
 
"We will measure the level of the chemokine CXCL12 [a signaling protein indicating there is injury that needs to be repaired] in these patient samples," he explains. "In addition, we will perform studies using mice in models of lung injury and isolated lung epithelial cells. We will be using a line of mice in which we have conditionally deleted the CXCR4 receptor in lung epithelial cells so that we can study its role in recovery from lung injury."