# Gender-specific effects of puberty on airway epithelial differentiation in asthma

> **NIH NIH K08** · MAYO CLINIC ROCHESTER · 2020 · $185,760

## Abstract

PROJECT SUMMARY/ABSTRACT
The main objectives of this K08 proposal are: 1) to foster the development of essential scientific and professional
skills that will allow the candidate, Dr. Sergio Chiarella, to achieve a long-term goal of becoming an independent
physician-scientist concentrating on the role of sex hormones in asthma pathogenesis, and 2) to investigate the
gender-specific effects of puberty-related systemic changes in sex hormones on airway epithelial differentiation
in asthma. Through laboratory experience, coursework in Northwestern University's Program in Public Health,
and the peer review process, Dr. Chiarella will gain expertise in experimental design, laboratory procedures,
data analysis, and scientific communication. Dr. Chiarella and his mentors at Northwestern University, Drs.
Sergejs Berdnikovs and Robert Schleimer, have designed a specific training plan that will allow Dr. Chiarella to
gain new knowledge and research skills in asthma. Asthma is a lung condition that causes tremendous morbidity
in the United States. There is ample epidemiological data showing that asthma prevalence and severity is
gender-specific and changes with puberty. Pre-pubertal boys have an increased prevalence of asthma and rate
of asthma exacerbations requiring hospitalization compared to pre-pubertal girls. Interestingly, this pattern
reverses with the onset of puberty and is known as the “asthma puberty switch”. The mechanisms involved in
the “asthma puberty switch” are poorly understood and understudied. Our preliminary data identify airway
epithelial differentiation as a critical target of sex hormones. Furthermore, our results show that the loss of airway
epithelial differentiation and function is gender-specific. Thus, we hypothesize that puberty-related systemic
changes in sex hormones promote a gender-specific effect on airway epithelial differentiation in asthma. To test
this hypothesis, we propose the following Specific Aims: 1) determine whether human normal and asthmatic
airway epithelium differentiation is gender-specific, and 2) determine the sex-specific effects of puberty on airway
epithelial differentiation and FGFR2 signaling in a murine “puberty switch” model of asthma. To specifically test
our hypothesis, we have developed a murine model of asthma which replicates the “asthma puberty switch” seen
in humans. We have also developed organotypic cultures of primary human airway epithelial cells to evaluate
the effects of estrogen on basal (less differentiated) and ciliated (more differentiated) epithelial cells. Finally, we
propose to identify the in vivo effects of sex hormones and FGFR2 on the airway epithelial barrier using
gonadectomized mice and Fgfr2fl/flFoxj1Cre mice, respectively. Successful execution of these aims will provide a
rigorous training program for Dr. Chiarella and uncover mechanisms involved in the “asthma puberty switch”.

## Key facts

- **NIH application ID:** 9996479
- **Project number:** 5K08AI141765-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Sergio E Chiarella
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $185,760
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996479

## Citation

> US National Institutes of Health, RePORTER application 9996479, Gender-specific effects of puberty on airway epithelial differentiation in asthma (5K08AI141765-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9996479. Licensed CC0.

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