# Modeling the premature airway with neonatal airway basal cells

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $223,511

## Abstract

PROJECT SUMMARY/ABSTRACT
Prematurity affects one in nine live births in the US and is a well-described risk factor for more severe and
recurrent respiratory infection during infancy and development of asthma. While it is clear that gestational age
at birth and age at infection influence severity of respiratory infection, host immunologic response, and risk of
long-term impact on lung development and function, our understanding of the mechanism driving these
associations remains poorly understand. Limited human infant autopsy studies have revealed aberrations in
the development and function of the airway epithelium, which serves as the first line barrier of defense against
inhaled pathogens. Models of newborn airway epithelium to study why premature babies are at higher risk of
infection and long-term ramifications, such as asthma, are lacking. We have developed a method of isolating
airway basal cells from respiratory secretions of newborns born prematurely and at term. These cells can be
expanded long-term and retain the ability to differentiate into pseudo-stratified airway epithelium making them
a powerful system to model pre-term and full-term airways. In preliminary experiments, cilia differentiated from
basal cells isolated from premature newborns are longer, beat slower, are less dense, and have decreased
linear mucociliary flow compared to full-term infant controls. We also found that developmental and immunity
related gene expression pathways are differentially expressed in pre-term basal cells. Using our innovative
method of isolating and growing epithelial cells derived from patient-specific basal cells we will study how
prematurity alters airway epithelium function. We will define the airway basal cell defect due to prematurity by
phenotyping pre- and full-term basal cells. Basal cells lines from pre- and full-term infants will be differentiated
in air-liquid interface culture and their differentiation potential, epithelial and cilliary function will be
comprehensively evaluated. We will also study how prematurity impacts the inflammatory response of
differentiated basal cells following RSV infection. Finally, gene co-expression networks and chromatin
accessibility will be used to identify the molecular signature associated with the basal cell prematurity defect
related to differentiation and RSV-infection response. The successful execution of these aims will establish
patient-specific derived airway basal cells as a practical and biologically relevant model system. In addition, our
results will provide a better understanding of the molecular mechanisms linking prematurity and early life RSV
infection with longer-term morbidities such as asthma, which are important for improving prevention and
treatment strategies.

## Key facts

- **NIH application ID:** 10427449
- **Project number:** 5R21AI156597-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Paul Hubert Lerou
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $223,511
- **Award type:** 5
- **Project period:** 2021-06-11 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427449

## Citation

> US National Institutes of Health, RePORTER application 10427449, Modeling the premature airway with neonatal airway basal cells (5R21AI156597-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10427449. Licensed CC0.

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