# Modulating macrophage-mediated Inflammation in cystic fibrosis

> **NIH NIH K08** · NATIONAL JEWISH HEALTH · 2020 · $157,789

## Abstract

ABSTRACT
Dr. Katherine Hisert's research is focused on understanding the role of macrophages in chronic
inflammatory lung diseases. Her long term goal is to become an independent physician scientist
engaged in clinical practice and translational research, with a focus on the disease cystic
fibrosis (CF). To achieve this goal, Dr. Hisert has defined a comprehensive career development
program that builds on her prior training in basic immunology research, including continued
development of her clinical skills in the UW Adult CF clinic, and instruction in computational
skills for analysis of large datasets generated by “omics” technologies. This training will enable
successful execution of the proposed studies, and prepare Dr. Hisert for a career in which she
can perform true bench to bedside research.
This research proposal investigates the potential use of a novel anti-inflammatory medication,
gallium nitrate, to improve disease outcomes by suppressing pro-inflammatory macrophage
responses. In a prior phase 1b clinical trial, gallium improved lung function in CF patients with
chronic bacterial airway infections, but whether gallium's therapeutic effect was due to its anti-
microbial properties or to anti-inflammatory properties was unclear. Dr. Hisert will test the
hypothesis that gallium reduces LPS- and bacterially mediated lung injury by suppressing pro-
inflammatory macrophage functions, and decreases airway inflammation in CF patients with
chronic infections. Aim 1 will determine which macrophage functions are altered by gallium, and
investigate the molecular mechanisms by which gallium attenuates macrophage inflammatory
responses. Aim 2 will use murine models to test if gallium protects against LPS-mediated lung
injury by suppressing pro-inflammatory macrophage responses in vivo. Aim 3 will take
advantage of a phase II clinical trial testing IV gallium's ability to improve lung function in CF
patients with chronic Pseudomonas infections. Dr. Hisert will isolate sputum macrophages
before and after patients receive IV gallium and investigate whether suppression of macrophage
pro-inflammatory gene expression is associated with improved lung function. Together these
studies will lead to a better understanding of gallium's anti-inflammatory effects, and explore the
possibility that suppressing pro-inflammatory macrophage functions could be therapeutic in CF,
and possibly other chronic inflammatory diseases.

## Key facts

- **NIH application ID:** 9893893
- **Project number:** 5K08HL136786-04
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Katherine B Hisert
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $157,789
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893893

## Citation

> US National Institutes of Health, RePORTER application 9893893, Modulating macrophage-mediated Inflammation in cystic fibrosis (5K08HL136786-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893893. Licensed CC0.

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