The host response to trauma andburns is a highly complex biological and pathological process that dependscritically upon the regulation of the human immuno-inflammatory response. Thislarge-scale collaborative project will apply high throughput biologicaldiscovery tools to identify important dynamic relationships, which regulate theintegration of these complex processes with the expectation that this newknowledge will ultimately impact the treatment of burn and trauma patients. Ahighly interactive group of investigators with overlapping interests and uniquetechnologies will contribute to the effort.
The specific aims are: (1)Determine the set of phenotypes seen in the immuno-inflammatory host responseto injury using a testable, consensus-derived paradigm which describes fourindependent clinical recovery trajectories of patients suffering from injury.(2) Identify gene expression patterns as a result of the immuno-inflammatoryhost response to injury in circulating peripheral leukocytes. (3) Identifyrelationships among genes, and the clustering of genes based upon temporalexpression patterns. (4) Determine the relevance and degree ofcompartmentalization in murine models of burn and severe trauma injury. Toaccomplish these overall scientific goals, there are multiple tasks proposed inthis large-scale collaborative project, and the accomplishment of these taskswill serve as milestones for the project. In addition to other milestones,these include: (1) Develop and publish SOPs for patient treatments, thehandling of patient samples, and the analytical procedures for protein andcellular studies; (2) Determine the immuno-inflammatory phenotypes of patientswith injury; (3) Determine potential relationships between genes orco-regulated genes in the host response to injury and suggest fruitful areasfor future investigation; (4) Determine the relevance of murine models to thehuman phenotypes of severe injury; (5) Determine whether there are correlationsbetween protein and genomic responses in subcellular populations versus thetotal pool of circulating peripheral leukocytes and between circulatingleukocytes and those in peripheral tissues; and (6) Determine and publish thefrequency of common SNPs in the ethnic groups who suffer from trauma. Thesemilestones will be accomplished through the development of an administrative,information dissemination and data coordination, and computational analysis andmodeling core, in addition to four scientific cores.
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