Inflammation and the Host Response to Injury

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DESCRIPTION (provided by applicant): The host response to trauma and burns is a highly complex biological and pathological process that depends critically upon the regulation of the human immuno-inflammatory response. This large-scale collaborative project will apply high throughput biological discovery tools to identify important dynamic relationships, which regulate the integration of these complex processes with the expectation that this new knowledge will ultimately impact the treatment of burn and trauma patients. A highly interactive group of investigators with overlapping interests and unique technologies will contribute to the effort. The specific aims are: (1) Determine the set of phenotypes seen in the immuno-inflammatory host response to injury using a testable, consensus-derived paradigm which describes four independent clinical recovery trajectories of patients suffering from injury. (2) Identify gene expression patterns as a result of the immuno-inflammatory host response to injury in circulating peripheral leukocytes. (3) Identify relationships among genes, and the clustering of genes based upon temporal expression patterns. (4) Determine the relevance and degree of compartmentalization in murine models of burn and severe trauma injury. To accomplish these overall scientific goals, there are multiple tasks proposed in this large-scale collaborative project, and the accomplishment of these tasks will serve as milestones for the project. In addition to other milestones, these include: (1) Develop and publish SOPs for patient treatments, the handling of patient samples, and the analytical procedures for protein and cellular studies; (2) Determine the immuno-inflammatory phenotypes of patients with injury; (3) Determine potential relationships between genes or co-regulated genes in the host response to injury and suggest fruitful areas for future investigation; (4) Determine the relevance of murine models to the human phenotypes of severe injury; (5) Determine whether there are correlations between protein and genomic responses in subcellular populations versus the total pool of circulating peripheral leukocytes and between circulating leukocytes and those in peripheral tissues; and (6) Determine and publish the frequency of common SNPs in the ethnic groups who suffer from trauma. These milestones will be accomplished through the development of an administrative, information dissemination and data coordination, and computational analysis and modeling core, in addition to four scientific cores.