# Sex differences in GPER-mediated mechanisms in allergic asthma

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2024 · $140,995

## Abstract

Project Summary
Asthma is a chronic inflammatory lung disease with a greater prevalence and severity in adult women than
men. Mounting evidence suggests that sex differences in asthma are related to female steroid sex hormones,
including estrogens. Estrogens have significant effects on lung function and responses to allergic challenge in
male and female lung, acting via receptors including the estrogen receptors α and β (ERα and ERβ) and the G
protein-coupled estrogen receptor (GPER). Prior studies from Dr. Silveyra’s laboratory (PI) have reported
influences of circulating sex hormone levels in the lung inflammatory response to allergen challenge, using
transgenic mouse models coupled with house dust mite (HDM) exposure. In this study, we will expand the
studies conducted in the parent grant to characterize intracellular signaling cascades mediated by the GPER in
the asthmatic bronchial epithelium. We hypothesize that the GPER mediates sex-specific responses activated
during HDM allergen challenge. To test this hypothesis, we will assess the effect of HDM challenge in GPER
signaling using human bronchial epithelial cells (HBEC) from asthmatic females and males (Aim 1). We will
also evaluate sex differences in GPER signaling pathways and second messengers activated by HDM and
estrogen in HBEC from asthmatic patients (Aim 2). The training plan of the proposed PDS diversity supplement
is integrated with the experimental approach and will enable the candidate to gain scientific knowledge and
communication skills, become proficient in molecular endocrinology and cell signaling bench skills, and obtain
preliminary data to apply for independent research funding as a postdoctoral fellow. Training and mentoring will
involve meetings with the primary mentor, Dr. Silveyra, her investigative team at Indiana University
Bloomington, two additional faculty advisors (Dr. Hocevar and Dr. Owora), coursework, and seminars.
Coursework will be supplemented with training in laboratory techniques to establish an understanding of the
pathophysiology of lung diseases and research design to assess sex-specific mechanisms and incorporating
sex as a biological variable. This combination of mentoring, bench training, and coursework will equip the
candidate to build his research career and work towards providing a better understanding of the molecular
mechanisms and pathways underlying lung diseases that differentially affect males and females.

## Key facts

- **NIH application ID:** 10993234
- **Project number:** 3R01HL159764-04S2
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Patricia Silveyra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $140,995
- **Award type:** 3
- **Project period:** 2021-07-10 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993234

## Citation

> US National Institutes of Health, RePORTER application 10993234, Sex differences in GPER-mediated mechanisms in allergic asthma (3R01HL159764-04S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10993234. Licensed CC0.

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