# Neutrophil extracellular traps in cystic fibrosis

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2020 · $638,879

## Abstract

Cystic fibrosis (CF) is still an incurable disease affecting 80,000 people worldwide. Current lack
of new CF therapies is due to our poor understanding of disease pathogenesis. Lung
complications are responsible for majority of CF mortality. CF airways are characterized by
chronic bacterial infections and robust infiltration of leukocytes called neutrophil granulocytes
(PMN). PMNs release their granule cargo and DNA to cause lung damage. Although release of
neutrophil-derived inflammatory mediators is of high clinical relevance in CF, its mechanism is
unknown. The long-term goal of this project is to determine how neutrophils could be
manipulated in CF for preventive and therapeutic purposes. The objective in this particular
application is to determine the mechanism and clinical relevance of neutrophil extracellular trap
(NET) release in CF. The central hypothesis is that NET formation is disadvantageous for the
host in CF: NETs cause lung damage without improving microbial clearance. This hypothesis
has been formulated based on strong preliminary data produced in the applicant’s laboratory.
The rationale for the proposed research is that, once the mechanism and clinical relevance of
NET formation in CF will be clear, interfering with it will enable development of innovative
PMN/NET-based CF therapies. The central hypothesis will be tested by 1) Determining the
complex mechanisms between P. aeruginosa and PMNs/NETs; 2) Determining how NET
formation affects pathology and infection in murine models of CF airway disease; and 3)
Strengthening the clinical relevance of NETs in CF airway disease using unique CF clinical
specimens. This research is innovative because it addresses an understudied but clinically very
relevant component of CF airway disease, uses novel tools uniquely developed by the applicant
laboratories to quantitate NETs, and employs mouse models that enable a unique mechanistic
understanding of the studied process. The proposed research is significant because it focuses
on a clinically relevant, unsolved question in CF by using primary human cells, CF clinical
samples and animal models. In summary, our proposal will deliver essential knowledge to
provide a major impact in the fields of CF airway inflammation, host-microbe interactions and
PMN biology. This knowledge can also lead to several potential translational applications.

## Key facts

- **NIH application ID:** 9898433
- **Project number:** 5R01HL136707-03
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Balazs Rada
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $638,879
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898433

## Citation

> US National Institutes of Health, RePORTER application 9898433, Neutrophil extracellular traps in cystic fibrosis (5R01HL136707-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9898433. Licensed CC0.

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