This application requests continued support for our longstanding Burn Trauma Center at Massachusetts General Hospital. Since the inception of the Center, its focus has continued to be the effects of systemic inflammation upon the metabolic response of the host to burn injury. In consideration of the application, our research program has identified opportunities for improvement and innovation within our Center projects and cores. We propose to take advantage of very new genomic data and its analyses, and computational biology methods from the NIGMS-funded Glue Grant Program, """"""""Inflammation and the Host Response to Injury"""""""" to study the innate inflammatory response postburn injury and its influence upon metabolism. This will be accomplished with the addition of the Stanford Genome Technology Center and Children's Hospital- Boston as new participating sites to complement the existing rich environment of MGH and Shriners Hospitals for Children-Boston. We propose to expand our """"""""team science"""""""" relationships with the SGTC and CH that already exist to create a new blend of academic expertise for sharing genomics and computational resources and ideas across geographical campuses. The focus of the program has been dramatically altered to include the study of metabolic changes associated with burn induced alterations in gene transcription and thus all of the projects in the previous center have been changed. To complement our expanding research endeavors, we have added exciting new advanced technologies that will provide more detailed knowledge in vivo and in vitro not previously possible. Thus, 4 projects are proposed: (1) molecular mechanisms of muscle wasting;(2) therapy for the amelioration of burn induced mitochondrial dysfunction;and molecular mechanisms of burn induced insulin resistance in (3) mice and (4) in non-human primates and burn patients. These synergistic studies will interact within and be supported by 5 cores, which provide administrative, technical, and analytical services. The Administration, Human Subjects and Animal Research Cores of the current center remain essentially unchanged. In the new Burn Trauma Center, the individual PET and Mass Spectrometry Cores have been combined and a new Computational Genomics Core has been added.
It is important to develop new strategies that can reverse the consequences of injury by restoring insulin sensitivity in the treatment of hospitalized patients. t is our belief that new mechanism-based therapies to enhance skeletal muscle insulin sensitivity might promote an anabolic state, restoring nutrient flux to a level compatible with optimal recovery from burn injury.
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