# Defining the cellular dynamics that orchestrate alveolar epithelial cell repair behaviors in live mammal

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $65,700

## Abstract

PROJECT SUMMARY
The mammalian lung has the capacity to repair itself following various injuries. Alveolar repair is
a dynamic and coordinated process whereby stem/progenitor cells in the lung undergo
differentiation into specialized cells to repair the damaged epithelium. Recent studies have
uncovered a distinct intermediate progenitor cell state that exists during the transition between
stem/progenitor cells and these specialized cells; however, the dynamic cellular behaviors and
molecular regulatory landscape that drives intermediate progenitor cell transitions toward repair
is poorly understood. Here, we propose two aims to dissect the cellular and molecular
mechanisms that control alveolar repair in vivo in the regenerating mammalian lung. First, we
investigate IPC transitions in the context of homeostasis instead of in acute injury models (virus
and bleo) as in the parent grant. We use single cell laser ablation to model the death of a single
cell, as occurs occasionally over a lifespan, and then investigate whether and how IPCs form in
response using fluorescent cell lineage-reporter mice. In the second aim, we turn to bleomycin-
induced lung injury – the most common mouse model for pulmonary fibrosis – but instead of using
single cell ‘omics approaches as in the parent grant, we take a spatial transcriptomics approach
that preserves the spatial architecture and cell-cell neighborhoods in alveoli. We apply spatial
transcriptomics at a time point that matches the parent grant and will allow integration of both
datasets. This project will generate extensive, high quality imaging and ‘omics datasets that
together with the parent grant enable quantitative and predictive models of the key regulatory
mechanisms that mammalian drive alveolar repair in vivo. Given that many of the cellular and
molecular mechanisms of lung biology are conserved between mouse and human, our findings
have the potential to uncover putative targets for modulating alveolar repair in the context of
human disease.

## Key facts

- **NIH application ID:** 11100894
- **Project number:** 3R01HL162629-02S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Maurizio Chioccioli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $65,700
- **Award type:** 3
- **Project period:** 2024-09-18 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11100894

## Citation

> US National Institutes of Health, RePORTER application 11100894, Defining the cellular dynamics that orchestrate alveolar epithelial cell repair behaviors in live mammal (3R01HL162629-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11100894. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*