? CORE C The Animal and Imaging Core will support Projects of the Program by providing logistic and scientific oversight, and performance of complex longitudinal animal experiments. Various murine asthma models representing different human asthma endotypes across the TH2-TH17 immune spectrum, including ovalbumin allergen, house dust mite, Aspergillus, high fat diet, and a combination of high fat diet plus house dust mite will be made available to projects to test the therapeutic effects of IL-17A pathway inhibition using peptidomimetics and sGC stimulators/activators on airway hyper-reactivity and inflammation. Pharmacokinetics studies of compounds will be performed to determine optimal route, dose and frequency of administration. Intranasal, oral gavage, intravenous and intraperitoneal injection, and nebulized administration are available. Measurements of airway hyper-reactivity, 4Dx airflow, tracheal densitometry, airway inflammation and airway remodeling will be performed to analyze drug effects. 4Dx Imaging is a cutting edge X-ray tomographic velocimetric quantification of regional airflow allowing us to identify specific part(s) of the lungs targeted by the new compounds. A cloud- based mouse laboratory information management system (mLIMS) will be used to record all experimental procedures and to securely store all mouse data. All required instruments and expertise are found in the Core or made available through collaboration, such as equipment for 4Dx imaging and pharmaceutical industry guidance for drug formulation for the various routes of administration. The Core expedites results and reduces cost of Projects through the use of shared model systems and, most importantly, assists in the generation of preclinical data to move new, more effective, therapeutics into the clinic. New model systems of endotypes of asthma, preclinical studies and airflow imaging increase overall translational innovation of the Program.
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