Severe traumatic injury results in biochemical and physiological changes that often lead to the development of nosocomial infection (pneumonia, wound infections, etc.) and remote organ (lung, kidney, liver) failure. Excluding those patients who succumb to their injuries and die in the immediate (≤ 1 hour) or early (≤ 24 hours) post-injury period, infection and organ failure (MODS; multiple organ dysfunction syndrome) are leading causes of death. Furthermore, infection and organ failure contribute to prolonged and resource intensive hospital stays. However, if these complications are not lethal, they do not appear to result in major long-term disabilities.
There have been considerable recent advances in characterizing the human genome, and we have now progressed from the notion of knowing the structure (the initial goal of the Human Genome Project was to sequence the entire human genome) to now understanding the function of our genetic material. Second, failure to consider individual variability, in the form of gene polymorphisms, may have reduced our ability to detect beneficial effects of novel therapies.
We are interested in both of these related phenomena and our research program aims to characterize genetic influences on the risk of and outcome from injury-related nosocomial infection and organ failure and to better characterize the nature of the inflammatory response to tissue injury. Our research program is directed at understanding the genetic basis for human variation in inflammatory responses and how these differences influence the clinical course of sepsis. We are also focusing on pathways that have traditionally been not considered “inflammation-related,” but appear to have important influences on how the inflammatory and innate immune responses are regulated in humans.