This Cell Culture and Animal Core is designed to support specific aims in each of the 4 projects in this revised Program Project Application. There are two specific aims.
The first aim i s to supply alveolar epithelial type II cells from human lungs, rat lungs, and mouse lungs to support the specific aims of Project 1 (Mostov), Project 2 (Engel), and Project 3 (Rosen). Our research group has had extensive experience in isolating, culturing, and studying pulmonary alveolar epithelial type II cells from human and rodent lungs under both normal and pathological conditions. This work has been especially productive in studying mechanisms of alveolar epithelial injury from P.aeruginosa ExoT and ExoS as well as establishing how the ADP ribosyl transferase domain of P.aeruginosa ExoT contributes to the biologic activities of the Pseudomonas organisms (Project 2, Engel). In addition, our recent work has established that human alveolar epithelial type II cells can be cultured in matrigel and induced to form 3-dimentional structures that resemble authentic alveolar-like structures. This accomplishment provides a major opportunity for novel studies of lung epithelial function under normal and pathologic conditions (Project 1, Mostov).
The second aim of this core, which represents an expanded direction, is to carry out in vivo mouse studies using pathologic models of lung injury to test specific hypotheses in Project 3 (Rosen) and Project 4 (Werb). These in vivo mouse experiments will use both infectious and non-infectious stimuli to test the effects on lung function and overall survival. Our research group has extensive experience with in vivo studies and there is considerable preliminary data that has been generated in testing specific hypotheses that a part of Project 3 (Rosen) and Project 4 (Werb).
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