Pulmonary Injury and Repair Center yields big return for UAB

Seed funding generates major UAB research projects geared toward treating lung injury from chemical attacks

sadis matalon wThe Pulmonary Injury and Repair Center at the University of Alabama at Birmingham has produced a major return on investment in its six years of existence. The Center, begun in 2008 with an initial investment of $140,000 from the UAB School of Medicine, Department of Anesthesiology and Southern Research Institute, has since received nearly $10 million in research funding from government and industry sources.

Those funds have spurred scientific research, recruited new faculty and produced new knowledge in treating lung injury, especially from chemical agents such as chlorine, ammonia and bromine.

Chlorine, ammonia and bromine are commonly used in various industrial applications and are routinely shipped across the country. Exposure to these agents could come as a result of a deliberate terror attack or from an inadvertent leak from a transportation mishap.

“Inhalation of these gases can cause extreme, possibly fatal injury to the lungs,” said Sadis Matalon, Ph.D., distinguished professor and vice chair for research in the Department of Anesthesiology, and director of the center. “Our research is geared toward finding countermeasures that could be employed to minimize pulmonary injury in the event of a chlorine, ammonia or bromine release, whatever the cause may be.”

The UAB center is part of the federal government’s CounterACT Program. Funded by the National Institutes of Health, CounterACT is a translational research program aimed at the discovery and/or identification of better therapeutic medical countermeasures and technologies against chemical threat agents. CounterACT was launched following the terror attacks on Sept. 11, 2001, as awareness grew of potential threats from chemical agents.

UAB is one of the few research institutions in the nation involved in countermeasure research against chlorine and ammonia, and it is the only site looking for agents that would be effective against bromine, according to Matalon.

“We are investigating multiple strategies to respond to lung injury in the event of exposure to these agents,” Matalon said. “We have identified compounds that in preliminary studies have been shown to prevent death after chlorine exposure, for example. Compounds such as antioxidants and nitrites also have promise in reducing or reversing the toxic effects of these agents.”

Matalon says one of the center’s strengths is its reach across the breadth of UAB. Investigators involved in the major projects come from multiple disciplines and include Victor Darley-Usmar, Ph.D., and Jianhua Zhang, Ph.D., pathology; Tim Ness, M.D., anesthesiology; Chad Steele, Ph.D., and Veena Antony, M.D., pulmonary medicine; Rakesh Patel, Ph.D., molecular and cellular pathology; Mohammad Athar, dermatology; and Anupam Agarwal, M.D., nephrology. Other prominent investigators include Edward Postlethwait, Ph.D., Michelle Fanucchi, Ph.D., and Giuseppe Squadrito, Ph.D., in the School of Public Health; as well as James and Diana Noah, Ph.D.s, with Southern Research Institute.

Matalon and Darley-Usmar received a grant to test the role of mitochondrial injury in the initiation and propagation of chlorine injury to the lungs. Matalon is also collaborating with Sven Eric Jordt, Ph.D., of Yale University, to test the effectiveness of a new class of anti-inflammatory agents to decrease chlorine injury.

Patel was recently funded by the CounterACT Program to test the efficacy of nitrites to decrease mortality and lung injury in chlorine-exposed animals. Athar is funded by CounterACT to develop therapeutic interventions of lewisite-mediated injury to the skin, which could contribute to lung injury. Ness was also funded to investigate whether local anesthetics administered post-exposure reduce pain.

“This is a critical issue because people who experience pain have decreased ability to walk away from the epicenter of a chemical attack,” Matalon said.

The center also played a role in the recruitment of prominent new faculty to UAB, says Matalon, including Victor Thannickal, M.D., chair of the Division of Pulmonary, Allergy and Critical Care Medicine, and Jean-Francois Pittet, M.D., professor of anesthesiology.

“The Pulmonary Injury and Repair Center has enhanced collaborations among basic and clinical investigators at UAB and has driven translational research in lung injury and repair,” Matalon said. “It has also strengthened existing interactions among researchers from UAB and Southern Research Institute. These interactions continue to improve our ability to attract new faculty interested in pulmonary research at UAB and to compete for extramural awards.”