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NEW APPROACH FOR STUDYING TRAUMATIC INJURY
Washington University School of Medicine in St. Louis is one of the primary institutions involved in the project, called “Inflammation and the Host Response”, which is supported by a five-year glue grant, a new type of funding from the National Institute of General Medical Sciences for large-scale, multidisciplinary pursuits. The NIGMS anticipates spending $37 million on the project. After severe trauma or stress, the body’s natural defense mechanisms can trigger an often-fatal cascade of cellular and physiological changes culminating in organ failure. As a result, critical illness and injury account for eight percent of deaths in the United States each year, typically taking the lives of young, otherwise healthy individuals. Until now, there has been no national agency systematically coordinating research and care for this population. “This grant gives us the first ever national agenda for injury and critical-care research,” says J. Perren Cobb, M.D., associate professor of surgery and principal investigator of the School of Medicine team. “Now we can use our resources efficiently by combining expertise to address this complex medical condition.” Though early treatment for severely injured trauma patients has improved dramatically since the introduction of advanced trauma life support in 1979, there is no evidence-based regimen of care once victims are transferred from the emergency room to the operating room and intensive care unit, according to Cobb. As a result, the mortality rate of injured patients in the ICU has barely improved in the past two decades. Without a better understanding of how the body’s cells, tissues and organs respond to injury, he doubts the situation will change. “We may actually be making things worse by trying to intervene during the body’s natural, adaptive response,” he explains. The group of 19 medical centers will compile an extensive database including demographic, genomic and physiologic information about patients with traumatic injuries. In the process, they plan to develop standard operating procedures for burn and trauma patients and to develop clinically relevant animal models. Trauma and the body’s response to injury may activate or inactivate thousands of genes. Scientists already have discovered a cluster of approximately 50 genes that regulates yeasts’ reaction to common forms of stress and injury. This new study will identify whether there is a similar list of genes that dictate the human body’s response. The problem is complex, however. Studies show that even mice with identical genes respond differently to the same type of injury. So the team also is studying how environmental factors influence the outcome. Gene activation triggers the formation of molecules called RNA. These molecules are messengers, translating the genetic code into proteins that carry out the gene’s commands. Research funded by the glue grant will investigate which elements of the genome, the transcriptome and proteome (proteins) improve survival after injury. The team also anticipates the discovery of new genes which, in turn, will help identify new targets for medical treatments. Washington University and Stanford University will lead the genomics component of the project. Key participants from the School of Medicine include Bernard Brownstein, Ph.D, research professor of molecular microbiology, Bradley D. Freeman, M.D., assistant professor of surgery, Richard S. Hotchkiss, M.D., associate professor of anesthesiology, medicine and surgery, and Gary D. Stormo, Ph.D., professor of genetics. If we can get complete information on a given individual at the genome, transcriptome and proteome level, we may be able to understand how organs interact after injury,” says Cobb. “Our ultimate goal is to understand and predict how an individual will respond to a given trauma and thereby help physicians choose the best treatment for each patient.”
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