# The role of neuropilin-2 in regulating environmental airways injury

> **NIH NIH K08** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $211,736

## Abstract

PROJECT SUMMARY/ABSTRACT
 The overall objective of this K08 Mentored Clinical Scientist Career Development Award Application is
to provide Dr. Moran with the essential skills and training necessary to become an independent physician
scientist. Dr. Moran and his mentor have designed a training plan with a rigorous research component along
with didactic instruction to establish the thought processes and principles necessary for successful career
development. With the knowledge and training acquired during this proposal, Dr. Moran will be well positioned
to conduct innovative translational studies into the mechanisms of environment-mediated lung diseases.
 Endotoxin (lipopolysaccharide, LPS) and ozone are common airborne pollutants that cause significant
respiratory disease morbidity and mortality. Lung innate immune cells, including alveolar macrophage (AM),
play a critical role in mediating inflammatory responses to inhaled endotoxin and ozone. The key molecules
that regulate innate immune responses to inhaled pollutants, and thus prevent pollutant-induced lung injury,
remain undefined. Dr. Moran has recently reported that neuropilin-2 (NRP2)—a pleiotropic protein with
membrane-bound and soluble isoforms—is upregulated by human and murine AM following LPS stimulation.
Interestingly, myeloid-specific ablation of NRP2 augments LPS-induced airway inflammation, indicating that
NRP2 negatively regulates inflammatory responses in the lungs. In addition, preliminary studies show that
ozone exposure increases NRP2 expression in murine lungs, suggesting that upregulation of NRP2 may be a
general anti-inflammatory response to inhaled environmental pollutants. For this proposal, Dr. Moran will
investigate the mechanisms by which NRP2 negatively regulates pollutant-mediated airway inflammation. In
Aim 1, he will determine if membrane-bound NRP2 directly inhibits LPS- and ozone-mediated activation of
human and murine AM. In Aim 2, he will determine if a soluble isoform of NRP2 attenuates LPS- and ozone-
induced airway inflammation in mice. In Aim 3, he will begin to translate his finding to humans by determining
the effects of inhaled LPS on sputum and serum NRP2 levels in healthy volunteers. These studies will be the
first to investigate the immunoregulatory role of NRP2 in pollutant-triggered airway inflammation, and may
reveal a new therapeutic target and/or biomarker for environmental airways injury.

## Key facts

- **NIH application ID:** 9927638
- **Project number:** 5K08ES029118-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Timothy Moran
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,736
- **Award type:** 5
- **Project period:** 2019-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927638

## Citation

> US National Institutes of Health, RePORTER application 9927638, The role of neuropilin-2 in regulating environmental airways injury (5K08ES029118-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9927638. Licensed CC0.

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