The overall goal of the Animal and Therapeutics Core (Core B) is to provide centralized and standardized procedures for the animal studies to test the efficacy of therapeutic agents proposed in each of Projects 1-4. The Core will provide two of the most commonly used murine lung fibrosis models: (1) Bleomycin-induced pulmonary fibrosis model;and (2) AdTGF- B1[223/225]-induced lung fibrosis model. The Core will also provide standardized drug delivery service through 3 different routes for 3 different candidate drugs for 4 Projects: (1) airway/non-surgical intratracheal delivery of ncRNAs (miRs and siRNAs) for Projects 3, 4;(2) systemic/oral administration (gavage) of an orally effective small molecule Src kinase inhibitor AZD0530 for Project 2;(3) intra-pleural delivery of ncRNAs and the small molecule Src kinase inhibitor for Project 1. The Core leader Dr. Rui-Ming Liu and several Project leaders have extensive experience with these animal models and with the techniques used for the drug delivery proposed. To provide the standardized service to all the projects, the Core will 1) Coordinate purchase, health services, and care for experimental animals;2) Provide logistical and technical support in ensuring that experimental regimens are implemented correctly;3) Prepare and determine the titers of the adenovirus that expresses constitutively active TGF-B1 (AdTGF- B1[223/225] );4) Conduct intranasal (for AdTGF- B1[223/225] and intratracheal (for bleomycin) instillation to induce lung fibrosis for all Projects;5) Administrate the therapeutic drugs through gavage, non-surgical intratracheal instillation, and intrapleural instillation daily or every other day as designed in each Project;6) Monitor and record abnormal responses in animals during experimental periods and euthanize animal if necessary. Centralization of these animal models and treatment procedures in the Core B will facilitate the work of the Principle Investigators of each Project and ensure that experiments with each Project will be performed using identical and standardized methods for animal handling. Centralization of these services therefore will allow for fewer total numbers of animals to be utilized (cost-effective) and for the comparison ofthe results between different drugs and different administration routes ofthe same drug.

Public Health Relevance

The overall goal ofthe Core B is to provide centralized and standardized procedures for the animal studies to test the efficacies of the potential therapeutic drugs proposed in 4 Projects in this Translational Project Program (T-PPG). The results from these studies may lead to the development of novel therapeutics for the treatment of Idiopathic Pulmonary Fibrosis, a devastating disease with no effective treatment.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-Q (M1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Alabama Birmingham
United States
Zip Code
Huang, Wen-Tan; Akhter, Hasina; Jiang, Chunsun et al. (2015) Plasminogen activator inhibitor 1, fibroblast apoptosis resistance, and aging-related susceptibility to lung fibrosis. Exp Gerontol 61:62-75
Thannickal, Victor J; Zhou, Yong; Gaggar, Amit et al. (2014) Fibrosis: ultimate and proximate causes. J Clin Invest 124:4673-7
Xie, Na; Cui, Huachun; Banerjee, Sami et al. (2014) miR-27a regulates inflammatory response of macrophages by targeting IL-10. J Immunol 193:327-34
Desai, Leena P; Zhou, Yong; Estrada, Aida V et al. (2014) Negative regulation of NADPH oxidase 4 by hydrogen peroxide-inducible clone 5 (Hic-5) protein. J Biol Chem 289:18270-8
Blackwell, Timothy S; Tager, Andrew M; Borok, Zea et al. (2014) Future directions in idiopathic pulmonary fibrosis research. An NHLBI workshop report. Am J Respir Crit Care Med 189:214-22
Hu, Meng; Che, Pulin; Han, Xiaosi et al. (2014) Therapeutic targeting of SRC kinase in myofibroblast differentiation and pulmonary fibrosis. J Pharmacol Exp Ther 351:87-95
Bai, Guangxing; Hock, Thomas D; Logsdon, Naomi et al. (2014) A far-upstream AP-1/Smad binding box regulates human NOX4 promoter activation by transforming growth factor-?. Gene 540:62-7
Hecker, Louise; Logsdon, Naomi J; Kurundkar, Deepali et al. (2014) Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance. Sci Transl Med 6:231ra47
Cui, Huachun; Xie, Na; Tan, Zheng et al. (2014) The human long noncoding RNA lnc-IL7R regulates the inflammatory response. Eur J Immunol 44:2085-95
Karki, Suman; Surolia, Ranu; Hock, Thomas David et al. (2014) Wilms' tumor 1 (Wt1) regulates pleural mesothelial cell plasticity and transition into myofibroblasts in idiopathic pulmonary fibrosis. FASEB J 28:1122-31

Showing the most recent 10 out of 13 publications