The major goal of this Core is to provide the principal investigators in this SCCOR grant with a comprehensive measurement of biological markers to assess and correlate ventilator associated lung injury (VALI) in human and animal models. Additionally, this Core will utilize the newly emerging, state of the art techniques of proteomics and genomics to integrate clinical and basic research pertaining to VALI. This Core supports the SCCOR's five research projects with services related to three key areas. First the Core will provide a centralized facility to analyze, compile and correlate levels of biomarkers such as interleukin-8 nitrotyrosinated proteins, von Willebrand Factor, surfactant proteins B, C, and D, protein carbonlys and lipid peroxidation products, isoprostanes and sphingosine-l-phosphate to endothelial and epithelial injury/leakiness in VALI. This classical approach will utilize plasma, serum and bronchial alveolar lavage (BAL) from HFV vs Conventional as well as from clinical patients with sepsis presenting either no acute lung injury or acute lung injury with the ventilator. The human studies will be compared to LPS - and hyperoxia/ventilator-induced alveolar lung injury in mice and VALI in the dog. Second, the NIH funded and newly established proteomics center at the Johns Hopkins University School of Medicine facility, will provide the necessary infrastructure and expertise to initiate and develop a proteomics approach to the Biomarkers Core. Drs. Robert Cole and Gerald Hart have assembled the personnel and state-of-the-art proteomics central facility to meet the immediate and long term needs of the scientific community at Hopkins. Specific competencies provided by the proteomics facility include: consultation and training of research faculty and technical personnel to differential imaging gel electrophoresis analysis, isotope-coded affinity tag analysis and application of Mass Spectrometry in obtaining structural information, identification and expression of new proteins, determine modifications, map cleavage sites and identify binding partners. Third, the recently established human genomics facility in the Pulmonary Division at the Johns Hopkins will provide the needed infrastructure and trained personnel to compare the phenotypic changes to gene expression in the endothelial and epithelial cells from human and animal models of VALI.
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