# Investigating the effects of airway injury on the alveolar compartment of the lung.

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2021 · $33,799

## Abstract

Abstract
The adult mammalian lung contains diverse populations of cells that coordinate self-renewal during homeostasis
and repair. However, these processes are dysregulated during lung diseases like chronic obstructive pulmonary
disease (COPD), asthma, idiopathic pulmonary fibrosis, COVID-19, and more. The lungs are composed of the
airways and alveolar space, two compartments with distinct functions. Each compartment contains a unique set
of epithelial cells, such as basal, secretory, and ciliated cells in the airways. The alveolar space, where gas
exchange occurs, is lined by alveolar type 2 cells (AT2s) and alveolar type 1 cells (AT1s). Additionally, emerging
studies have examined the regulation of lung epithelium by other cell types like immune, endothelial, and
mesenchymal cells. Among the mesenchymal cells that support lung epithelial stem cell niches are populations
of smooth muscle cells and fibroblasts that facilitate airway regeneration. In the alveoli, distinct fibroblast
populations have been identified that promote alveolar regeneration. Lung perturbations that affect specific
compartments of the lung require the activation of local epithelial-mesenchymal interactions to restore
homeostasis. However, the tissue-wide consequences of location-specific lung injuries is not well known. In my
work, I propose to study the effects of airway injury on the alveolar compartment of the lung. I hypothesize that
airway injury dysregulates homeostasis of the alveolar epithelium via alterations of the alveolar-associated lung
mesenchyme. I will use a murine model of airway injury (naphthalene), which selectively ablates club cells of the
airway epithelium, to determine if the alveolar epithelium or alveolar-supportive mesenchyme is dysregulated in
a tissue-wide response. My preliminary work demonstrates an increase in proliferative AT2s during the
regenerative phase of the airway injury response. Additionally, single cell RNA-sequencing of the lung
mesenchyme from these injured mice demonstrated transcriptional changes in response to the airway injury.
Through a combination of in vivo, in vitro, and computational approaches, I will 1) define the effect of airway
injury on the alveolar epithelium and 2) determine if alveolar Pdgfrα-expressing fibroblasts, a mesenchymal
population known to support alveolar regeneration, are altered in airway regeneration. Together, these studies
will provide novel insights into alveolar compartment disruptions that accompany airway repair, advancing our
understanding of how tissue-wide dysfunction occurs in complex lung diseases.

## Key facts

- **NIH application ID:** 10311135
- **Project number:** 1F31HL159919-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Irene Gar-Ling Wong
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,799
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10311135

## Citation

> US National Institutes of Health, RePORTER application 10311135, Investigating the effects of airway injury on the alveolar compartment of the lung. (1F31HL159919-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10311135. Licensed CC0.

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