# Pre-Clinical Models of VILI /ARDS Core

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2020 · $274,054

## 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 addition to its own space and
eq...

## Key facts

- **NIH application ID:** 9959502
- **Project number:** 5P01HL134610-03
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Jason X J Yuan
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $274,054
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959502

## Citation

> US National Institutes of Health, RePORTER application 9959502, Pre-Clinical Models of VILI /ARDS Core (5P01HL134610-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9959502. Licensed CC0.

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