# Role of Ezrin in Macrophages

> **NIH NIH R56** · YALE UNIVERSITY · 2020 · $412,285

## Abstract

PROJECT SUMMARY
Macrophages (MΦs) kill microorganisms, engulf dead cells and debris, and regulate the immune response.
They are thus gatekeepers of tissue health, including the lungs. The lung-tissue-resident MΦs (TR-MΦs) are
the interstitial and alveolar MΦs, which have complementary but distinct functions. In response to infections,
lungs are rapidly populated by waves of Ly6C+ circulating monocytes. In concert with TR-MΦs, these
monocytes fight the infection, then facilitate resolution of the inflammatory response. Many chronic lung
inflammatory diseases, including cystic fibrosis (CF), are associated with dysregulated MΦ function. Our long-
term goal is to understand how different lung MΦ populations contribute to lung hyper-inflammation and
infection, and to elucidate the biology of these distinct cell populations. The objective of this proposal is to
characterize ezrin’s role in monocyte/MΦ function. Our central hypothesis is that ezrin controls monocyte/MΦ
cortical actin organization and signal transduction events in response to inflammatory/infectious stimuli. These
cellular changes allow the MΦs to spread, move, phagocytize, and survive, thus shaping the magnitude and
quality of the lung immune response to infections. The rationale for these studies is that low ezrin levels have
been found in MΦs from patients with CF (our own work). Other investigators have also reported low ezrin
levels in blood cells from individuals with asthma. Thus, by elucidating the molecular mechanism by which ezrin
shapes lung MΦ functions, we could identify potential therapeutic targets for lung diseases. Our specific aims
will test the following hypotheses: (Aim 1) ezrin is necessary for monocyte/MΦ adaptation to the inflamed lung
microenvironment; (Aim 2) ezrin is needed for efficient phagocytosis of Staphylococcus aureus and
Pseudomonas aeruginosa, two microorganisms that CF patients fail to efficiently eradicate from their lungs;
(Aim 3) functional CFTR, the gene that causes CF when mutated, is needed to preserve normal ezrin levels
during MΦ activation. The contribution is significant since very little is known about ezrin’s role in regulating
lung MΦ activation. Our proposed research is innovative because we will use an unprecedented mouse model
in which ezrin is knocked out specifically in monocytes and MΦs. Thus, the proposed studies will investigate in
depth the consequences of ezrin loss in monocytes and MΦs during lung infection and inflammation.

## Key facts

- **NIH application ID:** 10202271
- **Project number:** 1R56AI153422-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Emanuela Marina Bruscia
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,285
- **Award type:** 1
- **Project period:** 2020-07-24 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202271

## Citation

> US National Institutes of Health, RePORTER application 10202271, Role of Ezrin in Macrophages (1R56AI153422-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10202271. Licensed CC0.

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