The purpose of Core B - Mouse Models of Fibroproliferative Lung Disease and Sample Core ? is to provide a resource for the Program investigators to conduct studies in both in vivo studies with mouse models and in vitro primary cell culture models. The Animal Core will be led by Dianhua Jiang, M.D, Ph.D., Professor of Medicine at Cedars-Sinai Medical Center, who is currently a PI of the Animal Core for the PPG program in the past years and has successfully supported all the projects. During the last funding period, the animal core has successfully supported the three projects and achieved the proposed goals, and generated multiple mouse strains required by all different projects and performed mouse modeling studies of lung fibrosis, resulting in several high impact publications and forming the basis for renewal of this Program grant. The responsibility of the Core includes providing training, standard operating procedures and facilitating for mouse models of interstitial fibrosis and CLAD and developing a core unit to support these projects. Core B will unify the three Projects by standardizing the aspects of animal experimentation and promote interactions among those involved in the Projects. Core B will conduct treatments required to induce fibroproliferative lung disease in mice and be responsible for outcome measurement. Fibroproliferative lung disease models will include intratracheal bleomycin, mouse model of CLAD, and human lung fibroblasts from IPF patients to immune compromised mice (SCID mice). Core B will isolate, fix and process mouse lung tissues and will perform standard histology staining for lung inflammation and fibrosis measurement. Additionally, the Core will serve to standardize histological scoring by implementing computer-automated assessment of lung hyaluronan, collagen, airway remodeling, epithelial cell apoptosis and inflammation. Core B will isolate, maintain and provide program investigators with primary cell lines including lung fibroblasts, macrophages and epithelial cells from mouse models. This facility serves to standardize culture methods across the three projects. The Core will also generate and maintain a mouse strain and results database, organize a tissue repository and histopathologic analysis. Centralizing the animal work in the Animal Core will reduce the cost of producing high-quality data and will facilitate interactions among the projects. Therefore, the Animal Core will play an important role in unifying the three Projects by standardizing all aspects of animal experimentation and promote interactions among investigators involved in the Projects to ensure the successful completion of studies proposed in this Program Project.

Public Health Relevance

The purpose of Core B - Animal Model and Sample Analysis Core ? is to provide a resource for the Program investigators to conduct studies in both in vivo studies with mouse models and in vitro primary cell culture models. Core B will unify the three Projects by standardizing all aspects of animal experimentation and promote interactions among investigators involved in the Projects to ensure the successful completion of studies proposed in this Program Project.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL108793-08
Application #
9957126
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Craig, Matt
Project Start
Project End
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
8
Fiscal Year
2020
Total Cost
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

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