# DUOX1 and Mitochondria in Obese  Asthma

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2020 · $532,400

## Abstract

PROJECT SUMMARY
The majority of severe asthmatics in the U.S. are obese, and obesity is a major risk factor for asthma. Both
chronic inflammation associated with asthma and metabolic alterations associated with obesity results in
increased oxidative stress and altered redox homeostasis, which likely contributes to disease pathology. Our
recent studies identified the NADPH oxidase DUOX1, a major enzymatic source of reactive oxygen species
(ROS) within the respiratory epithelium, as a mediator of innate type 2 inflammatory responses to allergens and
of clinically relevant features of allergic airway disease in a mouse model of allergic asthma. Preliminary studies
of human obese allergic asthmatics or mice with diet-induced obesity (DIO) further indicate that obesity is
associated with enhanced production of type 2 cytokines (IL-33, IL-13) in response to allergen challenge.
Moreover, preliminary data indicate close and reciprocal interactions between airway epithelial DUOX1 and
mitochondrial ROS production, which is associated with enhanced redox-mediated activation and mitochondrial
translocation of the tyrosine kinases Src and epidermal growth factor receptor (EGFR), and suggests that
enhanced DUOX1 activation in combination with altered mitochondrial integrity and function results in worsened
redox perturbations in obese asthma. The Specific Aims of this proposal are 1) to determine the effect of obesity
on airway DUOX1 expression and activation and its role in innate cytokine responses to allergen challenge; 2)
to assess the interactions between DUOX1 and mitochondrial ROS production, ATP production or glycolysis,
and the role of mitochondrial targeting of EGFR/Src pathways; and 3) to evaluate the functional importance of
DUOX1-mitochondrial interactions in obese allergic airways disease. Collectively, these studies will address how
enhanced DUOX1 in combination with mitochondrial dysfunction due to obesity contributes to epithelial redox
perturbations and altered epithelial allergen responses, as a critical mechanism of enhanced or immune
responses and airway remodeling in obesity-related asthma.

## Key facts

- **NIH application ID:** 9971572
- **Project number:** 5R01HL138708-04
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** ALBERT VAN DER VLIET
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $532,400
- **Award type:** 5
- **Project period:** 2017-08-03 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971572

## Citation

> US National Institutes of Health, RePORTER application 9971572, DUOX1 and Mitochondria in Obese  Asthma (5R01HL138708-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9971572. Licensed CC0.

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