# Animal Core

> **NIH NIH P01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $56,168

## Abstract

Idiopathic pulmonary fibrosis (IPF) is a most enigmatic fatal lung disorder. Although significant progress
has been made in our understanding of IPF pathogenesis, the molecular mechanisms underlying the
pathophysiology of IPF remain poorly understood. Moreover, although two anti-fibrosis drugs, pirfenidone and
nintedanib, have been approved by FDA for the treatment of IPF, the efficacy of these drugs for the later stages
of the disease is uncertain and neither drug reduces IPF mortality (1-4). Based on the results from the Cycle I
of this Translational Program Project (tPPG), we will, in this renewal tPPG, test a hypothesis that redox-metabolic
control of myofibroblast activation, modulated by innate/adaptive immune mechanisms (alveolar macrophages
and B-cells), leads to progressive fibrosis. Specifically, we will test the safety and efficacy of a small molecule
inhibitor of NOX1/4 in a Phase IIb clinical trial (Project 1; Duncan, Project Leader) and explore the mechanisms
by which NOX4 regulates pro-fibrotic metabolic programs in myo-Fbs (Project 2; Thannickal, Project Leader).
Based on new convincing data, we will also investigate the role of NOX4 in regulating cellular metabolism and
pro-fibrotic phenotypes of alveolar macrophages (Project 3; Carter, Project Leader) and the role of auto-Abs (B-
cells) in regulating epigenetic control of pro-fibrotic genes in activated myo-Fbs (Project 4; Sanders, Project
Leader). To aid in testing the hypothesis and developing the therapeutic drugs for IPF, the overall objective of
the Animal Core is to provide centralized and standardized procedures for the animal studies proposed in
Projects 2, 3, and 4. Specifically, the Core will provide two of the most commonly used murine lung fibrosis
models, bleomycin-induced and asbestos-induced lung fibrosis models, for Project 2, 3, and 4 to test the
therapeutic potential of GKT137831 for lung fibrosis and the underlying mechanism. The core will also provide
standardized service for drug (GKT137931) delivery through oral gavage. Moreover, the Core will provide
standardized technique service for the measurement of lung injury and fibrosis by micro CT image and mouse
lung function by FlexiVent. Centralization and standardization of the procedures will lead to high quality,
reproducible, and comparable results among individual projects, which are essential for the success of this tPPG.

## Key facts

- **NIH application ID:** 9980985
- **Project number:** 5P01HL114470-08
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** RUI-MING LIU
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $56,168
- **Award type:** 5
- **Project period:** — → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980985

## Citation

> US National Institutes of Health, RePORTER application 9980985, Animal Core (5P01HL114470-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9980985. Licensed CC0.

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