Publication by Pharmacy Professor Zhao Elucidates Mechanisms of Lung Repair in Acute Lung Injury

09/03/2014
Zhao

Research at The Ohio State University College of Pharmacy suggests that the expression of a gene can assist in cell repair in acute lung injury. A team led by Xiaoli Zhao­, assistant professor of pharmacology at Ohio State, conducted the study that published its first research paper with funding from a five-year, $1.9 million National Institutes of Health Heart, Lung, and Blood Institute grant. Zhao’s resulting findings, “TRIM72 is Required for Effective Repair of Alveolar Epithelial Cell Wounding,” were published in the latest issue of the American Journal of Physiology – Lung Cellular and Molecular Physiology.

TRIM72, a tripartite motif protein, assists in the repair of alveolar epithelial cells in acute lung injury (ALI), a lung injury syndrome characterized by a life-threating low level of oxygen in the blood. Dr. Zhao started to develop this project in collaboration with Rolf D. Hubmayr at Mayo Clinic Rochester, a leading expert in critical care medicine and acute lung injury.

“We are excited about our finding that TRIM72 works to repair alveolar epithelial cells, and overexpression of the TRIM72 gene shows a protective effect following over-ventilation insults,” said Zhao. “This finding provides novel insights for the pathogenesis of ALI.”  

ALI, or acute respiratory distress syndrome (ARDS), is a complex syndrome seen in critical care departments and has an estimated mortality rate of 24 – 41 percent. The cause and pathology of ALI are diverse and wide spreading and currently no bio-therapies targeting any particular signaling pathway have proven clinical efficacy.

Mechanical ventilation, which is often required to sustain the life of ALI patients, has the potential risk to aggravate injuries in cases of ALI. Zhao’s team and collaborators will continue to investigate their proposed, novel therapeutic method to target the membrane repair pathway in in vivo models to evaluate and optimize this treatment strategy for ALI.

“Our next step is to further investigate time course and molecular partners for TRIM72 to repair lung cells, which is critical for identification of the best treatment window and avoiding contradictions for the treatment of ALI,” said Zhao. “We believe that our results are very promising in moving towards better therapy options for patients.” 

Zhao’s other collaborators on the project included Miyuki Nishi and Hiroshi Takeshima (Kyoto University), Beiyun Zhou and Per Flodby (University of Southern California), Konstantin Shilo (Pulmonary Pathology, OSU) and Samir N. Ghadiali (Bioengineering, OSU). Seong Chul Kim, a postdoctoral researcher in Zhao’s lab, and Tom Kellett, a second-year PhD student in the pharmaceutical science program of the College of Pharmacy, are co-first authors on the paper. College of Pharmacy professors Lane Wallace and Jack Yalowich edited the manuscript.

“The environment in the division of pharmacology at the College of Pharmacy is very supportive and played a major role in our team’s success,” said Zhao.