Researchers at the University of Illinois at Chicago College of Medicine have been awarded more than $11.7 million to study the pathology of severe lung injury.
The study, part of a multi-pronged investigation into acute lung injury, or ALI, is funded by the National Heart, Lung and Blood Institute, one of the National Institutes of Health.
ALI and its even more severe form, acute respiratory distress syndrome, result from pulmonary edema -- leaky blood vessels -- and inflammation. Direct lung injury from infection or indirect injury from trauma, sepsis, pancreatitis, transfusions, radiation or drug overdose can trigger ALI. It is fatal almost 40 percent of the time.
"We are now ready to address the very important, clinically relevant aspects of the pathobiology of ALI and investigate novel therapeutic approaches," said Natarajan, program director and professor of pharmacology and medicine at UIC, who has been studying ALI for 20 years. Natarajan also co-directs the Institute for Personalized Respiratory Medicine at UIC with Dr. Joe G.N. "Skip" Garcia, University of Illinois vice president for health affairs, UIC vice chancellor for research and Earl M. Bane Professor of Medicine.
The NIH Program Project Grant is an interdisciplinary investigation of a bio-active lipid called sphingosine-1-phosophate, or S1P, and its receptors and their role in lung cell signaling, inflammation and injury caused by sepsis or radiation.
One project, led by Natarajan, will use animal and cell-culture models to investigate how S1P is generated inside cells and how it exerts a protective effect in ALI -- an effect which Garcia, Natarajan and their collaborators had demonstrated previously in animal models of ALI.
A second project, headed by Garcia, will investigate the role of S1P receptors in ALI.
"Dr. Garcia brings cutting-edge expertise in genomics, genetics and clinical medicine to the project," Natarajan said, "and will address the very important question of modulating the S1P receptors to thwart ALI."
Dr. Steve Dudek, associate professor in pulmonary, critical care and sleep medicine at UIC, will lead a third project, working with researchers at the City University of New York to develop analogues of S1P and another molecule to increase their therapeutic potential.
"Our goal ultimately is drug development, working through the Institute for Personalized Respiratory Medicine to actually test some of these analogues in the clinical setting," said Natarajan.
The final project, led by Dr. Jeffrey Jacobson, associate professor in pulmonary, critical care and sleep medicine, and Dr. Ralph Weichselbaum, chief of services in radiation oncology at UIC and chairman of radiation and cellular oncology at the University of Chicago, will investigate ALI using the radiation-induced lung injury animal model.
"Radiation also can cause ALI in people," said Natarajan. "This study is likely to facilitate the development of tailor-made S1P analogues alone or in combination with statins to combat different forms of ALI."
Natarajan said the team "wants to quickly move from bench to bedside, finding ways to minimize the lung injury, and propel the patients on a path of rapid recovery."