# Airway Epithelial Resilience to Environmental/Oxidative Threats: Intersection with Type-2 Biology and Racial Inequity

> **NIH NIH F30** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $42,636

## Abstract

Project Summary/Abstract
Although asthma is common, the morbidity/mortality rates for Black Americans are unacceptably
high. Gene-by-environment interactions likely play important roles, such that greater exposures
to exogenous oxidative stressors, especially unhealthy air in many US Black communities could
adversely affect outcomes. These exposures also intersect with various non-biologic factors,
including institutional racism. “Redlining,” or discriminatory mortgage lending and form of
institutional racism, provides historic/geographically validated regions of interest across the US to
study the intersection of airway biology with racial and environmental inequity. Endogenously,
epithelial cells can resist exogenous oxidative stress, like air pollutants, but at the expense of
reduced glutathione (GSH). In preliminary data, our lab showed that reduced GSH is depleted in
epithelial cells of Type-2 Hi asthma, secondary to activation of the 15-lipoxygenase 1 (15LO1)
pathway which leads to higher endogenous oxidative stress. 15LO1-Hi conditions also promote
autophagy, potentially modulating the release of extracellular vesicles (EVs), including exosomes,
while decreasing the release of free/’toxic” mitochondrial DNA. Unfortunately, factors that further
stress epithelial cells overcome these programmed resiliency factors to induce ferroptosis, a
recently identified form of cell death that promotes the release of “free” mtDNA associated with
further reductions in EVs. We hypothesize that environmental hazards that increase exogenous
oxidative stress, such as higher levels of exposure to air pollution as associated with racism,
intersect with T2 asthma-associated, 15LO1-dependent endogenous oxidative stress in airway
epithelial cells. This convergence depletes resiliency factors (GSH, “healthy” mtDNA, EVs) and
increases inflammation and susceptibility to ferroptotic death, which worsens asthma
outcomes. To address this hypothesis, we propose 2 aims: 1) determine the effect of increasingly
toxic environments on intracellular and intercellular resiliency factors, with emphasis on the
intersection with asthma biology ex vivo and 2) determine the singular and combinatorial effect of
endogenous and exogenous oxidative stress on intracellular and intercellular resiliency factors in
vitro. My goal is to gain cell biology, epidemiology, and bioinformatics training, facilitating my
transition to an independent scientist with the necessary skill set to address the environmental
health effects of racism on asthma through cutting-edge translational science. Through this
fellowship, I will also receive clinical asthma, research ethics, and public health training, which
will pave my path to success. The data obtained here will help me in my next career stages and
also form the foundation for asthma interventions targeting communities damaged by racism.

## Key facts

- **NIH application ID:** 10313748
- **Project number:** 1F30ES033557-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Alexander James Schuyler
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $42,636
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313748

## Citation

> US National Institutes of Health, RePORTER application 10313748, Airway Epithelial Resilience to Environmental/Oxidative Threats: Intersection with Type-2 Biology and Racial Inequity (1F30ES033557-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10313748. Licensed CC0.

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