The proteomics core will provide state-of-the-art protein characterization and quantitation in support of all four of the projects in this Acute Lung Injury SCCOR program, including the two clinical projects (projects 1 and 2) and the two experimental projects (project 3 and 4). In addition, the core will develop a comprehensive human lung proteomics database, initially using alveolar epithelial type II cells and then alveolar epithelial type I cells. This comprehensive database will provide knowledge that is essential for the interpretation of the bronchoalveolar lavage (BAL) and pulmonary edema fluid proteomic studies in the clinical projects. The mouse studies will be used to carry out profiling in the BAL fluid with each of the manipulations to assess if some of the same proteins are being altered by TGF-beta and IL-1beta (project 4) as are altered by EPCR, PAR1, or APC (project 3). The results in the APC mouse studies in project 4 would have direct relevance to the APC studies in the clinical project 1. We anticipate a large number of proteins to either increase or decrease in their expression levels in response to disease processes. However, therapeutic interventions that modulate disease progression are likely to alter expression of only a subset of these proteins. By comparing the response with and without treatment, it is likely that a relatively small number of candidate proteins can be identified that are likely to be critically important in the pathogesis of acute lung injury. For human studies, it is important to obtain this data now before any new therapy becomes standard and the comparative data becomes impossible to acquire.
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