Clinical Translational Core (Core B): Abstract The acute respiratory distress syndrome (ARDS) affects 100-200K people in the U.S. yearly leading to death in approximately 35% of patients. Rather than the result of respiratory failure, mortality in ARDS patients typically results from multisystem organ failure or from hospital acquired infections. Recently, studies demonstrate that many patients with ARDS will experience a period of immune suppression or immunoparalysis following the early hyperinflammatory phase of the illness, the mechanistic and phenotypic basis of which is unclear. Therefore, this Program Project Proposal (P01) focuses on elucidating the molecular mechanisms underlying immune suppression in ARDS in order to identify novel pathways for therapeutic targeting. The Clinical Translational Core (Core B) is designed to optimize the translational exploration of the mechanisms identified in the P01 Projects by providing: 1) de-identified human tissue and fluid samples (collected via a prospective IRB approved Registry and Biospecimen Repository) to project investigators for verification of human relevance of novel findings from the bench or from murine models, 2) a novel platform for translational investigation in the ex-vivo lung perfusion system whereby mechanistic pathways and potential therapeutic interventions demonstrating promise in murine models can be tested in a human system before administration to patients, and 3) expert statistical support and data management for Project Investigators. All four primary projects detailed within the proposal will utilize Core B to focus on discovery of novel immune suppressing pathways in key cell types involved in the pathogenesis of ARDS: type II alveolar pneumocytes (Projects 1 and 2) and inflammatory cells including the macrophages, myeloid cells, and host-protective lymphocytes (Projects 3 and 4). In providing these services, Core B integrates tightly and interacts closely with all projects comprising the P01 proposal.
Clinical Translational Core (Core B): Narrative The ultimate goal of the studies proposed in this Program Project Proposal (P01) is to identify new molecular targets for the treatment of acute respiratory distress syndrome (ARDS) by elucidating the molecular mechanisms underlying the development of immunosuppression or immune paralysis. The Clinical Translational Core is designed to provide project investigators with access to clinical data, tissue, and bodily fluid samples from prospectively phenotyped subjects with ARDS or control subjects with non-pulmonary critical illness in order to support translation of basic and animal discoveries into human relevance.
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