# EPHEDRA: Enhanced PHthisic by Environmental Disruptors of Resolution Agonists

> **NIH NIH R56** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $510,710

## Abstract

Abstract
 It now widely appreciated that uncontrolled inflammation is a unifying component in many widespread
diseases 1, including chronic lung diseases 2,3. Inhalational exposure to respirable particulate matter can be an
important precipitant or exacerbate of lung inflammation. From our earlier results, the resolution of
inflammation is known today as an active process 4. There are several new families of specialized pro-
resolving mediators (SPM) identified and characterized in acute inflammation 5. These protective mediators are
enzymatically produced and are agonists at specific receptors transducing cell type specific functional
responses critical in tissue resolution. Resolution programs of the inflammatory response are essentially
uncharted in environmental health and medicine. Fundamental information is critically needed on the impact of
new environmental agents within the resolution response and whether they perturb resolution to trigger chronic
inflammatory responses and infections. Here, the B.D. Levy, C.N. Serhan and P. Demokritou labs unite to
collaborate for NOT-ES-20018 and propose an innovative study entitled EPHEDRA: Enhanced PHthisic by
Environmental Disruptors of Resolution Agonists, focusing on elucidating the impact of potentially hazardous
environmental agents presented to the airway as nanoparticles on newly uncovered resolution programs that
govern phagocyte functions and the return to homeostasis. Failed resolution or its disruption can lead to
sustained lung inflammation and inefficient clearance of microbial pathogens, including viruses and bacteria.
 This proposal will test an innovative hypothesis, namely that specific environmental agents prime for
sustained lung inflammation by disrupting cellular and molecular pro-resolving mechanisms that also
increase susceptibility to lung infections; and replacement of resolvins and/or other specialized pro-
resolving mediators that are potent agonists for resolution responses in lungs are required to protect
lungs from hazardous environmental agents and restore effective microbial clearance. To test this
hypothesis, we propose 3 specific aims to:
1) Determine the impact of environmental and engineered nanoparticles (NP) on the resolution of lung
inflammation,
2) Establish the impact of NP disruptors of resolution on viral host responses and post-influenza secondary
 bacterial pneumonia, and
3) Determine the impact of NP exposure on macrophage efferocytosis, SPM production, pro-resolving
 receptors and SPM rescue.
 Results from these studies will elucidate fundamental mechanism(s) in the resolution of inflammation
 that are susceptible to disruptive environmental agents and toxic to resolution.

## Key facts

- **NIH application ID:** 10662073
- **Project number:** 1R56ES033250-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Bruce D Levy
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $510,710
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10662073

## Citation

> US National Institutes of Health, RePORTER application 10662073, EPHEDRA: Enhanced PHthisic by Environmental Disruptors of Resolution Agonists (1R56ES033250-01A1). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/10662073. Licensed CC0.

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