# Targeting metabolic pathways in lung injury

> **NIH NIH F32** · JOHNS HOPKINS UNIVERSITY · 2022 · $79,294

## Abstract

PROJECT SUMMARY
Acute respiratory distress syndrome (ARDS) affects over 200,000 individuals in the US and over 3 million
worldwide each year. This highly lethal syndrome can occur due to various types of lung injury (for example
pneumonia, inhalational injury, or sepsis). Thirty to forty percent of patients with this condition will die – usually
of multiorgan failure. There are no available pharmacologic therapies for ARDS and treatment is essentially
supportive. Novel therapies for this condition are therefore urgently needed. Studies of ARDS pathophysiology
have shown that lung injury is highly inflammatory, but numerous different anti-inflammatory therapies that have
been tested in clinical trials have failed to reduce mortality from this disease. A potential novel approach to
treating ARDS may be found in the nascent field of immunometabolism, which has shown that activation of
immune cells (such as the lung macrophages and neutrophils that are known to play an important role in ARDS)
leads to major metabolic changes that are necessary to support pro-inflammatory responses. Understanding the
metabolic pathways that support detrimental inflammation during acute lung injury could lead to treatments for
ARDS that hasten resolution of inflammation and promote wound healing through modulation of metabolism.
In this proposal, metabolic pathways that are altered during lung injury will be studied in animal models as well
as in human biospecimens. Our preliminary data has shown that two particular metabolites–myo-inositol and
glutathione—rapidly drop in abundance in three different animals models of acute lung injury. Moreover, treating
mice with myo-inositol or glutathione in one of our models—pneumonia due to Streptococcus pneumoniae, also
known as “pneumococcus”—significantly improved their survival. Myo-inositol and glutathione can both act as
antioxidants, so we hypothesize that they are depleted during lung injury because of oxidative stress.
Supplementation with these metabolites may improve survival during pneumococcal infection by reducing
oxidative injury. In Aim 1 of this project, the cellular basis of the changes in myo-inositol and glutathione
metabolism will be examined by separating immune cells and non-immune cells (e.g. endothelial and epithelial
cells) from the lungs of mice with pneumococcal pneumonia and measuring metabolite abundance in these
separated cell populations. In Aim 2, we will examine whether treatment of mice with myo-inositol or glutathione
reduces levels of oxidative stress in the pneumococcal pneumonia model and whether this correlates with
reduced inflammation and lung injury. In Aim 3, we will measure levels of metabolites in de-identified
bronchoalveolar lavage fluid samples from patients with ARDS due to COVID-19 pneumonia compared to
healthy controls to determine whether myo-inositol and glutathione levels fall during human ARDS as they do in
our mouse models. Completing this project will provide fundamental i...

## Key facts

- **NIH application ID:** 10536749
- **Project number:** 1F32HL160199-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Kevin Shenderov
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $79,294
- **Award type:** 1
- **Project period:** 2022-09-15 → 2023-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536749

## Citation

> US National Institutes of Health, RePORTER application 10536749, Targeting metabolic pathways in lung injury (1F32HL160199-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10536749. Licensed CC0.

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