# Role of FABP5 in COPD Exacerbations

> **NIH NIH R01** · NATIONAL JEWISH HEALTH · 2024 · $597,510

## Abstract

PROJECT SUMMARY
Inflammation underlies the pathogenesis of many chronic lung diseases. Thus, defining mechanisms by which
pulmonary inflammation is regulated and resolved is of high clinical importance. Understanding those
mechanisms is especially relevant to chronic obstructive pulmonary disease (COPD), a condition that typically
develops following decades of cigarette smoking (CS) and in which repeated respiratory infections are linked to
non-resolving inflammation and can cause disease flares (COPD exacerbations). Lung macrophages are critical
for both initiation and resolution of inflammation, and the control of exacerbations. They can adopt different
phenotypes (i.e., pro-inflammatory or pro-repair) that are characterized by an interplay of transcriptional and
metabolic programming dictating macrophage function and ensuring tissue integrity. We previously
demonstrated that fatty acid binding protein 5 (FABP5) mediates pro-repair macrophage function via interaction
with the nuclear receptor Peroxisome Proliferator-Activated Receptor γ (PPARγ) and identified a novel single
nucleotide polymorphism (SNP), rs202275, linked with a FABP5 enhancer region and COPD exacerbations.
However, the critical role of the FABP5/PPARg axis and the genetic variation rs202275 (T) in macrophage
phenotypic programming and whether they can be targeted for therapeutic purposes remains unknown. We
propose 3 aims to interrogate the role of the FABP5/PPARg axis in macrophage pro-repair phenotype relying on
1) metabolism, 2) transcription, and 3) function of lung macrophages. This work will provide an in-depth clinically
relevant understanding of the mechanisms by which decreased FABP5 leads to chronic lung inflammation in
COPD exacerbations, identify a novel target to reverse chronic inflammation in COPD, and validate the
repurposing of FDA approved PPARγ agonists used in type 2 diabetes.

## Key facts

- **NIH application ID:** 10982119
- **Project number:** 2R01HL141264-05
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Fabienne Gally
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $597,510
- **Award type:** 2
- **Project period:** 2019-06-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10982119

## Citation

> US National Institutes of Health, RePORTER application 10982119, Role of FABP5 in COPD Exacerbations (2R01HL141264-05). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10982119. Licensed CC0.

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