The purpose of Core B - Mouse Models of Fibroproliferative Lung Disease - is to provide a resource for investigators to conduct studies in mice. The Director of Core B, Julia K. L. Walker, Ph.D., is a physiologist who has extensive experience with mouse models of lung inflammation. The Co-director, Dianhua Jiang, M.D., Ph.D., is an expert in lung cell and molecular biology who has extensively studied mechanisms that control lung flbrosis. A major strength of this program project grant is that each project is centered around the common theme that endogenous matrix components drive a pro-flbrofic fibroblast phenotype and that this underiies fibroproliferative lung diseases. By conducting standardized mouse models of pulmonary fibroproliferation, including a bleomycin model of pulmonary fibrosis and a chronic allergen-induced model of asthmatic airway remodeling, the Animal Core will facilitate interactions among the three projects and enhance their synergy. Additionally, the Core will coordinate histological preparation and analysis of fixed lung so that this evaluation will also be standardized. The Animal Core will work with investigators to provide lung fissue from which primary fibroblast and other cell cultures can be made. In summary, the Animal Core will provide the investigators with a facility where mice, experimental equipment and methods of analysis are consolidated and that is supported by skilled staff with expertise in all aspects of lung disease development and assessment. Centralizing the animal work in the Animal Core will reduce the cost of producing high-quality data and will facilitate interactions among the different projects. Therefore, the Animal Core will play an important role in the successful completion of work proposed in this Program Project.

Public Health Relevance

Fibroproliferative lung diseases such as pulmonary fibrosis and chronic asthma represent a serious unmet medical need and no therapies have been approved by the FDA to treat fibrosing lung diseases. The goal of the Animal Core is to provide investigators with standardized mouse models of lung fibrosis. These studies will improve the mechanistic understanding of fibrosing lung diseases and hopefully lead to novel therapeutic strategies to treat them.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL108793-03
Application #
8680338
Study Section
Special Emphasis Panel (ZHL1-CSR-S)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$346,185
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
Liang, Jiurong; Liu, Ningshan; Liu, Xue et al. (2018) MK2 Inhibition Attenuates Fibroblast Invasion and Severe Lung Fibrosis. Am J Respir Cell Mol Biol :
Xie, Ting; Wang, Yizhou; Deng, Nan et al. (2018) Single-Cell Deconvolution of Fibroblast Heterogeneity in Mouse Pulmonary Fibrosis. Cell Rep 22:3625-3640
Xie, Ting; Liang, Jiurong; Geng, Yan et al. (2017) MicroRNA-29c Prevents Pulmonary Fibrosis by Regulating Epithelial Cell Renewal and Apoptosis. Am J Respir Cell Mol Biol 57:721-732
Liang, Jiurong; Zhang, Yanli; Xie, Ting et al. (2016) Hyaluronan and TLR4 promote surfactant-protein-C-positive alveolar progenitor cell renewal and prevent severe pulmonary fibrosis in mice. Nat Med 22:1285-1293
Yu, Yen-Rei A; Hotten, Danielle F; Malakhau, Yuryi et al. (2016) Flow Cytometric Analysis of Myeloid Cells in Human Blood, Bronchoalveolar Lavage, and Lung Tissues. Am J Respir Cell Mol Biol 54:13-24
Li, Yuejuan; Liang, Jiurong; Yang, Ting et al. (2016) Hyaluronan synthase 2 regulates fibroblast senescence in pulmonary fibrosis. Matrix Biol 55:35-48
Xu, Yan; Mizuno, Takako; Sridharan, Anusha et al. (2016) Single-cell RNA sequencing identifies diverse roles of epithelial cells in idiopathic pulmonary fibrosis. JCI Insight 1:e90558
Liang, Jiurong; Jiang, Dianhua; Noble, Paul W (2016) Hyaluronan as a therapeutic target in human diseases. Adv Drug Deliv Rev 97:186-203
Xie, Ting; Liang, Jiurong; Liu, Ningshan et al. (2016) Transcription factor TBX4 regulates myofibroblast accumulation and lung fibrosis. J Clin Invest 126:3063-79
Dong, Yingying; Geng, Yan; Li, Lian et al. (2015) Blocking follistatin-like 1 attenuates bleomycin-induced pulmonary fibrosis in mice. J Exp Med 212:235-52

Showing the most recent 10 out of 23 publications