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
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.
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| Mehta, Manan M; Weinberg, Samuel E; Steinert, Elizabeth M et al. (2018) Hexokinase 2 is dispensable for T cell-dependent immunity. Cancer Metab 6:10 |
| Brazee, Patricia L; Dada, Laura A (2018) Splice Wars: The Role of MLCK Isoforms in Ventilation-induced Lung Injury. Am J Respir Cell Mol Biol 58:549-550 |
| Koch, Clarissa M; Chiu, Stephen F; Akbarpour, Mahzad et al. (2018) A Beginner's Guide to Analysis of RNA Sequencing Data. Am J Respir Cell Mol Biol 59:145-157 |
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| Kong, Hyewon; Chandel, Navdeep S (2018) Regulation of redox balance in cancer and T cells. J Biol Chem 293:7499-7507 |
| Hsiao, Hsi-Min; Fernandez, Ramiro; Tanaka, Satona et al. (2018) Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1?. J Clin Invest 128:2833-2847 |
| Wang, Zheng; Divanyan, Alex; Jourd'heuil, Frances L et al. (2018) Vimentin expression is required for the development of EMT-related renal fibrosis following unilateral ureteral obstruction in mice. Am J Physiol Renal Physiol 315:F769-F780 |
| Lu, Ziyan; Casalino-Matsuda, S Marina; Nair, Aisha et al. (2018) A role for heat shock factor 1 in hypercapnia-induced inhibition of inflammatory cytokine expression. FASEB J 32:3614-3622 |
| Amarelle, Luciano; Lecuona, Emilia (2018) A Nonhospitable Host: Targeting Cellular Factors as an Antiviral Strategy for Respiratory Viruses. Am J Respir Cell Mol Biol 59:666-667 |
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