UF, national experts seek genetic understanding of trauma, inflammation

 

GAINESVILLE, Fla. (Oct. 13, 2003) — University of Florida genetics researchers trying to understand the body’s response to burns and trauma are part of a national consortium of scientists united by a five-year, $37 million grant from the National Institute of General Medical Sciences.

            A common reaction to injury is inflammation, a necessary defense mechanism that causes a mosquito bite to itch or a sore throat to ache. But it is a mechanism that can turn deadly. Excessive inflammation and sepsis, a life-threatening infection, are common reactions to severe burns or traumatic injury.

            Researchers want to understand the genetic features that enhance a patient’s recovery, as well as the elements that cause people to die, sometimes weeks after the injury occurred. Identifying those factors could help physicians choose the best treatment, a decision that could be the difference between life and death.

Scientists will sample whole blood and other available tissues from trauma patients in an effort to correlate molecular markers with white blood cell behavior, and ultimately, with patient outcome. Clinical researchers from about 13 hospitals participating nationwide will collect samples from burn patients, trauma patients and normal volunteers.

The project brings together a large group of scientists from leading academic medical centers across the country, including the University of Florida, where the laboratory of Henry Baker, Ph.D., serves as one of three analytical genomics research cores. Further, scientists in the molecular genetics and microbiology department and the surgery department are providing the projectwide protein analyses that will be used to characterize the patient population. Members of the College of Medicine’s surgery department are responsible for collecting, storing and processing all blood and tissue samples.

In addition to Baker’s lab, genomic labs at Washington University in St. Louis and Stanford University will handle project data for the consortium.

            “The vast majority of patients who experience severe trauma or burn injury actually do well,” said Lyle Moldawer, Ph.D., a surgery professor in the College of Medicine. “They’re resuscitated at the scene, taken to the hospital, have an uneventful recovery and they’re discharged. But there’s a certain fraction who go on to develop complications that lead to organ failure and death, which is the most common cause of death after traumatic injury — sepsis and multisystem organ failure. So the goal of the grant is to use functional genomics as a tool to identify those patients who, after severe trauma and burn injury, will go on to manifest this multisystem organ failure. It’s a way to better characterize the nature of the immuno-inflammatory response to trauma. Our current tools aren’t very good.”

            Science has never before taken a look at the subtleties of the body’s response to injury at a genomewide level, Moldawer said. One of the important goals of the project is to develop standard operating procedures for burn and trauma patients. Currently, physicians have a limited number of standards to follow in the immediate care of burn and trauma patients.

            “In general, medicine has gotten very good at stabilizing trauma patients and getting them to the intensive care unit,” said Baker, associate chairman of the UF Genetics Institute and interim chair of molecular genetics and microbiology. “But really over the last 50 years, once patients are in the unit, the challenge for the physicians is to just support the patient, and the patient will either get better or succumb to the problem. The issue is to discover whether we can use functional genomics to identify patients who experience severe trauma and burn injury who will go on to develop multisystem organ failure, sepsis and death.”

            Ronald G. Tompkins, M.D., a surgeon and biomedical engineer at Massachusetts General Hospital, is leading the project.

            “Hundreds of thousands of Americans die from injury and millions more are hospitalized each year, at societal costs of more than $200 billion annually,” Tompkins said. “Traditional research approaches have not yielded the medical breakthroughs needed for further significant medical advances in this area.”

            According to Tompkins, the collaboration provides a unique opportunity to understand the body’s molecular reactions to injury, including inflammation.

            “From this understanding of how the body controls inflammation, we expect to be able to not only increase the likelihood of survival, but also to favorably impact length of hospitalization and cost of treatment, as well as quality of life,” Tompkins said.

            The consortium includes burn and trauma surgeons, critical care physicians, geneticists, cell biologists, physiologists, biostatisticians, mathematicians, bioinformatics specialists and biomedical engineers.

The National Institute of General Medical Sciences originally conceived of such large-scale grants after leaders in the scientific community emphasized the importance of confronting intractable biological problems with the expertise and input of large, multifaceted groups of scientists.

            Also joining in the effort are researchers from Harvard Medical Center, the Massachusetts Institute of Technology, the University of Washington’s Harborview Medical Center in Seattle, the University of Texas, the University of Colorado Health Sciences Center, Northwestern University, Loyola University, Pacific Northwest National Laboratory and the University of Alabama at Birmingham.

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Contact: John Pastor at 352-392-3845 or jpastor at vpha.health.ufl.edu