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.
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.
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