# Mitochondrial Redox Perturbations in Obese Allergic Asthma

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2022 · $780,069

## Abstract

Obesity is a risk factor for severe, uncontrolled asthma; the mechanisms causing asthma in obesity remain
unclear, and so there is a lack of therapies for this patient population. Mitochondrial function is altered in both
asthma and obesity, and oxidative stress is increased in obese compared with lean asthmatics. This project will
address mitochondrial reactive oxygen species (mROS) signaling in obese allergic asthma.
We have preliminary data that manipulating mROS signaling might inhibit allergic responses, particularly in
obesity. We also have preliminary data implicating signaling of mROS through peroxiredoxin-3 (a
mitochondrial peroxide target) and the transcription factor FoxM1 (a member of Forkhead box (Fox) family of
transcription factors) in obese allergic asthma.
This proposal will address the following hypothesis: mitochondrial redox perturbations induce oxidation of
peroxiredoxin 3 which interacts with FoxM1 to enhance allergic airway inflammation and reactivity in obese
allergic asthma; directly targeting mROS, and oxidant signaling through Prx3-FoxM1, will be effective for the
treatment of obese allergic asthma.
We will initially determine the functional significance of mROS production from airway epithelial cells from 4
patient groups (lean controls, obese controls, lean allergic asthmatics and obese allergic asthmatics), and the
efficacy of inhibiting mROS production in mouse models of lean and obese allergic asthma using a
mitochondrial targeted anti-oxidant, MitoQ.
We will then determine the functional significance of Prx3 oxidation and interaction with FoxM1 in airway
epithelial cells isolated from 4 patient groups (lean controls, obese controls, lean allergic asthmatics and obese
allergic asthmatics), and the efficacy of inhibiting Prx3 and FoxM1 relay signaling in mouse models of lean and
obese allergic asthma
Finally we will perform a randomized, double-masked, placebo-controlled trial of the mitochondrial targeted
anti-oxidant MitoQ in 40 patients with obesity and poorly controlled allergic asthma at two asthma research
centers (University of Vermont, and Duke University).
The results of these studies will show how mitochondrial ROS regulate allergic inflammation in obese asthma,
and lead directly to novel therapies for the treatment of allergic asthma in obese patients.

## Key facts

- **NIH application ID:** 10455740
- **Project number:** 5R01HL136917-05
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Vikas Anathy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $780,069
- **Award type:** 5
- **Project period:** 2018-09-07 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455740

## Citation

> US National Institutes of Health, RePORTER application 10455740, Mitochondrial Redox Perturbations in Obese Allergic Asthma (5R01HL136917-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10455740. Licensed CC0.

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