# Pre-Clinical Models of VILI /ARDS Core

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2021 · $246,648

## Abstract

SUMMARY: 
Core C, Pre-Clinical Models of ventilator-induced lung injury (VILI)/acute respiratory distress syndrome 
(ARDS), is designed to provide PPG investigators with rigorously defined and reproducible murine models of 
VILI, a two-hit lung injury model induced by exposure to both a ventilator and lipopolysaccharide (LPS) 
administration (VILI+LPS) that better mimics ARDS in patients, and an E. coli pneumonia model. Core C will 
comprehensively generate, manage and provide all animal-related experiments, resources, and expertise by 
accomplishing 6 specific aims. Specific Aim #1 will provide a complete range of expertise, training, 
equipment, and data analysis tools to extensively study the pathogenic mechanisms in preclinical models of 
murine lung injury. We will employ state-of-the-art techniques to a) characterize the role of various intracellular 
signaling cascades in regulating lung endothelial cell (EC) barrier function, b) determine the effects of specific 
interventions to provide insight into the efficacy and mechanisms of novel therapeutic strategies; and c) 
facilitate the translation of basic research to clinical interventions. Toward these goals, Core C will first provide 
validated quantitative measurements of vascular permeability and inflammation. Specific Aim #2 will house 
and care for the genetically-engineered mice and to generate novel transgenic and knockout mice (e.g., 
inducible endothelium-specific and lung epithelium-specific conditional knockout mice). Specific Aim #3 will 
examine selective siRNAs or pharmacological agents for target signaling cascades as potential therapeutic 
strategies and approaches for preclinical models and ultimately, for ARDS. Specific Aim #4 will be to provide 
performance of specific experimental strategies involving VILI, VILI+LPS (“two-hit”), E. coli pneumonia models 
of ARDS as well as gene-specific rescue interventions. Specific Aim #5 will evaluate the function of ARDS- 
associated single nucleotide polymorphisms (SNPs) and sites of functional protein post-translational 
modification (PTM), utilizing mutated cDNA (high efficiency expression plasmids) targeting the lung 
endothelium (with ACE antibody-conjugated liposome) in the endothelial conditional knockout mice. Specific 
Aim #6 will provide high quality shared data for data storage and well-preserved lung tissue samples to 
individual projects for more sophisticated molecular and cellular assays. Core C will centralize all mice-related 
work across all three projects of this program, including generating new strains, breeding and housing of mice, 
generating preclinical VILI/ARDS and VILI+LPS models, accessing therapeutic effects of siRNAs and 
chemicals, performing lung inflammation assessment, and providing tissue samples and freshly dissociated 
murine lung vascular endothelial cells to each project for specific assays (including immunohisto- and 
immunocytochemistry, western blot analysis, fluorescent microscopy). In addi...

## Key facts

- **NIH application ID:** 10094244
- **Project number:** 5P01HL134610-04
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Jason X J Yuan
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $246,648
- **Award type:** 5
- **Project period:** 2018-02-05 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10094244

## Citation

> US National Institutes of Health, RePORTER application 10094244, Pre-Clinical Models of VILI /ARDS Core (5P01HL134610-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10094244. Licensed CC0.

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