In the injured lung, damage to the alveolar epithelium initiates repair mechanisms that if successful are associated with a recovery of lung function and survival but if unsuccessful result in pulmonary fibrosis and death or disability. The three projects that comprise this proposal examine mechanisms by which the alveola epithelium responds to stimuli present in the milieu of the injured lung and the consequences of these responses for alveolar epithelial repair or fibrosis. To take advantage of the power of mouse genetics, all of the investigators propose studies in mouse models of acute lung injury or fibrosis. The physiology and mouse core will provide the project investigators with standard models of lung injury and fibrosis and perform detailed physiologic measurements of alveolar epithelial function in these models. The core will also breed and genotype transgenic and knockout mouse populations for the project investigators and oversee the expression of Cre recombinase in the lung epithelium. This program project is committed to examining the role of the alveolar epithelium in the development of lung injury. To achieve this goal in the in vivo mouse model, we will create transgenic mouse systems that will allow for the inducible expression or knockout of specific proteins in the entire lung epithelium, or exclusively in Type II or Type I alveolar epithelial cells

Public Health Relevance

Moving important research discoveries made using isolated cells to the bedside of patients requires the use of animal models. The mouse provides an ideal model to study human diseases because of the relative ease with which it can be genetically manipulated. We plan to provide project investigators with state of the art physiologic and genetic tools to study Acute Lung Injury, The Acute Resniratorv Distress Svndmme fARDS^ and luno fihrosis in mice.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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Northwestern University at Chicago
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Budinger, G R Scott; Mutlu, Gökhan M (2014) ?2-agonists and acute respiratory distress syndrome. Am J Respir Crit Care Med 189:624-5
Camargo Jr, Carlos A; Budinger, G R Scott; Escobar, Gabriel J et al. (2014) Promotion of lung health: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases. Ann Am Thorac Soc 11 Suppl 3:S125-38
Weinberg, Samuel E; Chandel, Navdeep S (2014) Futility sustains memory T cells. Immunity 41:1-3
Kim, Seok-Jo; Cheresh, Paul; Williams, David et al. (2014) Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells. J Biol Chem 289:6165-76
Chandel, Navdeep S (2014) Mitochondria as signaling organelles. BMC Biol 12:34
Radigan, Kathryn A; Morales-Nebreda, Luisa; Soberanes, Saul et al. (2014) Impaired clearance of influenza A virus in obese, leptin receptor deficient mice is independent of leptin signaling in the lung epithelium and macrophages. PLoS One 9:e108138
Chiarella, Sergio E; Soberanes, Saul; Urich, Daniela et al. (2014) ??-Adrenergic agonists augment air pollution-induced IL-6 release and thrombosis. J Clin Invest 124:2935-46
Keller, Michael J; Lecuona, Emilia; Prakriya, Murali et al. (2014) Calcium release-activated calcium (CRAC) channels mediate the ?(2)-adrenergic regulation of Na,K-ATPase. FEBS Lett 588:4686-93
Queisser, Markus A; Dada, Laura A; Deiss-Yehiely, Nimrod et al. (2014) HOIL-1L functions as the PKC? ubiquitin ligase to promote lung tumor growth. Am J Respir Crit Care Med 190:688-98
Cummins, Eoin P; Selfridge, Andrew C; Sporn, Peter H et al. (2014) Carbon dioxide-sensing in organisms and its implications for human disease. Cell Mol Life Sci 71:831-45

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