# Basal cells in airway and alveolar remodeling

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2024 · $592,860

## Abstract

Abstract
Acute respiratory viral infections represent an enormous societal and economic burden with the potential for
persistent declines in lung function among recovering patients. Severe infections trigger abnormal repair
processes and inflammation leading to remodeling of small airways and alveoli, impaired pulmonary function
and death in particularly susceptible individuals. These features of lung injury, repair and remodeling of small
airways and alveoli, are recapitulated in mouse models of H1N1 influenza (PR8) virus infection, wherein alveolar
injury leads to expansion of basal cells (BC) in airways and replacement of damaged alveolar epithelium. In
preliminary studies we provide evidence that nascent BC are derived from a serous-like subset of airway
secretory cells (intralobar serous or IS). We have identified an unexpected role for TAp63 in the specification of
nascent BC and that Lcn2 expression by “activated” AT2 cells of the PR8-infected lung contributes to BC
recruitment to injured alveoli. Finally, we show that recruitment of nascent BC to damaged alveolar regions
impacts the proliferative activity and clonal behavior of surviving alveolar type 2 (AT2) cells. Aims of this proposal
seek to test the overarching hypothesis that PR8-elicited nascent BC that ultimately colonize damaged alveolar
regions are derived from IS cells through a fate transition that is regulated by TAp63. Furthermore, we
hypothesize that AT2-derived Lcn2 mediates BC recruitment to injured alveoli where they regulate local Wnt
signaling and inhibit AT2 cell proliferation. Aim 1 will examine the role of TAp63 and its downstream targets in
IS>BC specification following PR8-induced lung injury. Aim 2 will investigate roles for AT2-derived Lcn2 in
recruitment of PR8-elicited BC to injured alveoli. Aim 3 will test the hypothesis that nascent BC recruited to sites
of parenchymal injury suppress the regenerative capacity of surviving AT2 cells and will explore roles for BC-
derived Wnt ligands in this process. Completion of these aims will provide new insights into cellular and molecular
mechanisms of repair in acute lung injury and how persistent activation of these repair pathways might contribute
to tissue remodeling in lung disease.

## Key facts

- **NIH application ID:** 10831425
- **Project number:** 5R01HL159160-03
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Barry R Stripp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $592,860
- **Award type:** 5
- **Project period:** 2022-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831425

## Citation

> US National Institutes of Health, RePORTER application 10831425, Basal cells in airway and alveolar remodeling (5R01HL159160-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10831425. Licensed CC0.

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