# Resue of CF phagocyte function with CFTR modulator therapy

> **NIH NIH R01** · EMORY UNIVERSITY · 2023 · $531,709

## Abstract

PROJECT SUMMARY
Why patients with cystic fibrosis (CF) continue to suffer from chronic bacterial infections despite
new medications that improve CF transmembrane conductance regulator (CFTR) function is
unknown. The objective of this proposal is to define how new triple combination highly effective
CFTR modulator therapy (HEMT) alters CF phagocytic cell function. The rationale underlying
this proposal is that our prior work demonstrates that CF macrophages and neutrophils are
integral to the inability of patients with CF to clear bacterial infections through several
dysfunctional mechanisms. Many of these mechanisms are only partially amenable to
treatment with currently available CFTR modulators. The central hypothesis is that CF
phagocytic cell function is dependent on functional CFTR, can be restored by HEMT, and
correlates with clinical responses. The central hypothesis will be tested by pursuing three
specific aims: 1) Determine whether HEMT changes functional CFTR in CF macrophages and
neutrophils; 2) Assess HEMT-treated macrophage and neutrophil functional responses to
infection; and 3) Correlate individual clinical responses with phagocytic cell function. We will
pursue these aims using unique models and assays that include human macrophages and
neutrophils and association with well-characterized clinical data. The proposed research is
significant because a precise understanding of how CF macrophage and neutrophil function is
regulated by HEMT would allow novel, personalized treatment approaches to infection in CF
and other diseases. The expected outcome of this work will establish a mechanistic framework
to enable us to target and correct defective killing of bacteria in CF. The long-term goal is to
develop therapeutics that modulate host immune responses in CF patients to mitigate chronic
infection and inflammation. Ultimately, we will translate this new knowledge into a new treatment
paradigm that uses innovative host-directed therapies to combat bacterial infections.

## Key facts

- **NIH application ID:** 10797778
- **Project number:** 7R01HL158747-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Amal O Amer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $531,709
- **Award type:** 7
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10797778

## Citation

> US National Institutes of Health, RePORTER application 10797778, Resue of CF phagocyte function with CFTR modulator therapy (7R01HL158747-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10797778. Licensed CC0.

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