UF, national experts seek genetic understanding of trauma, inflammation

University of Florida genetics researchers trying to understand the body’s response to severe 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 wound to swell or a sore throat to ache. But it is a natural defense mechanism that can often turn deadly.

Excessive inflammation and sepsis, in response to a life-threatening infection, are common effects of severe burns or traumatic injury.

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

Scientists will sample whole blood and other available tissues from severely injured and burned patients in an effort to correlate the gene expression patterns in blood leukocytes and other tissues 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 College of Medicine’s molecular genetics and microbiology and surgery departments are providing protein analyses that will be used to better characterize the patient population. Members of the 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. “They’re resuscitated at the scene, taken to the hospital, have an uneventful recovery and are successfully discharged. But there’s a certain fraction of these patients who go on to develop complications that often lead to sepsis, organ failure and death, which is the most common cause of late death following traumatic injury. So one of the goals of the program is to employ gene expression patterns as a tool to more accurately identify those patients who, after severe trauma and burn injury, will go on to manifest this multisystem organ failure. It is also an effort to better characterize the nature of the immuno-inflammatory response to trauma, and to identify new therapeutic targets. Our current tools to characterize the injured patients rely primarily on physiological measurements, and aren’t very good at describing the immuno-inflammatory response. Science has never before taken a look at the subtleties of the body’s inflammatory response to injury at a genome wide level.”

One of the important additional goals of the project is to develop standard operating procedures for the management of 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 become very good at stabilizing trauma patients and getting them to the hospital and into the intensive care unit,” said Baker, associate chairman of the UF Genetics Institute and interim chairman of molecular genetics and microbiology. “But over the past 50 years, we have been less successful at treating the critically ill patient, and current therapies are primarily supportive. The current challenge is to discover whether we can use functional genomics to better identify those patients with 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 not only to 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 School, the Massachusetts Institute of Technology, the University of Washington’s Harborview Medical Center in Seattle, the University of Texas, Washington University in St. Louis, the University of Colorado Health Sciences Center, Northwestern University, Loyola University, Pacific Northwest National Laboratory and the University of Alabama at Birmingham.