Inflammation and the Host Response to
Injury
(U54-GM62119)
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; and (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.
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