# Therapeutic Targeting of the Myofibroblast in Fibrotic Lung Disease

> **NIH NIH P01** · TULANE UNIVERSITY OF LOUISIANA · 2022 · $1,194,222

## Abstract

PROJECT SUMMARY
 Fibrosis involving the airways, vasculature, alveoli, and pleura is seen, to varying degrees, in a number of
clinical syndromes, including asthma, subphenotypes of chronic obstructive pulmonary disease, pulmonary
hypertension, and idiopathic pulmonary fibrosis (IPF). IPF is the most enigmatic and fatal of the fibrotic lung
disorders. Despite the recent approval of two drugs, survival has not significantly improved. Pulmonary
fibrosis represents a complex tissue response to lung injury that involves a number of cell types, mediators,
and signaling pathways. In just over the last few years, several new concepts in disease pathogenesis have
emerged; these include metabolic reprogramming, epigenetics, immune modulation, macrophage biology and
the invasive/apoptosis-resistant phenotype of myofibroblasts (myoFbs). Each of these concepts/paradigms is
addressed in this renewal application of this tPPG. Work conducted during Cycle I of this tPPG has validated
the pro-fibrotic effects of the reactive oxygen species (ROS)-regenerating enzyme, NADPH oxidase 4 (NOX4),
and identified circulating plasma biomarkers of oxidative stress in human subjects with IPF. In Project 1, we
will conduct a Phase IIb clinical trial of the safety and efficacy of a NOX1/4 inhibitor in IPF using multiple
biomarkers and physiologic measures as primary and secondary end-points. Project 2 will test the hypothesis
that redox-metabolic reprogramming of myoFbs accounts for the observed pro-fibrotic effects of NOX4. Based
on emerging data on macrophage-myoFb interactions in fibrosis, Project 3 will test the hypothesis that NOX4
modulates macrophage mitochondrial ROS and metabolism to polarize alveolar macrophages to a pro-fibrotic
phenotype. Project 4 will test the novel hypothesis that B-cell derived autoantibodies epigenetically reprogram
Fbs to an anti-apoptotic phenotype. Together, this tPPG will elucidate critical links between cellular redox
control and metabolic reprogramming, uncover novel regulatory mechanisms of macrophage polarization, and
illuminate previously unrecognized connections between innate/adaptive immunity, epigenetics and lung
fibrosis. Importantly, this tPPG will advance a novel anti-fibrotic drug therapy that more specifically targets
redox biology in IPF, which will enable future Phase III clinical trials.

## Key facts

- **NIH application ID:** 10473592
- **Project number:** 5P01HL114470-11
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Victor J. Thannickal
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,194,222
- **Award type:** 5
- **Project period:** 2013-09-16 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10473592

## Citation

> US National Institutes of Health, RePORTER application 10473592, Therapeutic Targeting of the Myofibroblast in Fibrotic Lung Disease (5P01HL114470-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10473592. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*