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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL071643-10
Application #
8446405
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
10
Fiscal Year
2013
Total Cost
$338,079
Indirect Cost
$115,576
Name
Northwestern University at Chicago
Department
Type
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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
Radigan, Kathryn A; Nicholson, Trevor T; Welch, Lynn C et al. (2018) Influenza A Virus Infection Induces Muscle Wasting via IL-6 Regulation of the E3 Ubiquitin Ligase Atrogin-1. J Immunol :
Coates, Bria M; Staricha, Kelly L; Koch, Clarissa M et al. (2018) Inflammatory Monocytes Drive Influenza A Virus-Mediated Lung Injury in Juvenile Mice. J Immunol 200:2391-2404
Sala, Marc A; Chen, Cong; Zhang, Qiao et al. (2018) JNK2 up-regulates hypoxia-inducible factors and contributes to hypoxia-induced erythropoiesis and pulmonary hypertension. J Biol Chem 293:271-284
Sala, Marc A; Balderas-Martínez, Yalbi Itzel; Buendía-Roldan, Ivette et al. (2018) Inflammatory pathways are upregulated in the nasal epithelium in patients with idiopathic pulmonary fibrosis. Respir Res 19:233
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
Dela Cruz, Charles S; Wunderink, Richard G; Christiani, David C et al. (2018) Future Research Directions in Pneumonia. NHLBI Working Group Report. Am J Respir Crit Care Med 198:256-263

Showing the most recent 10 out of 202 publications