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

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $436,350

## 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 (Aim 1) we
will utilize a permanent lung imaging window system to track the emergence, live behaviors and terminal
differentiation of individual intermediate progenitor cells over time during alveolar repair. Second (Aim 2) we will
utilize combined scRNA-seq and scATAC-seq together with advanced dynamical analysis and machine learning
techniques to define the cellular state space (gene expression and chromatin accessibility), cellular trajectories
and regulatory landscape of transitioning intermediate progenitor cells. We will perform both aims using
complimentary in vivo lung injury models and fluorescent report mice in order to track the mechanisms that are
unique to intermediate progenitor cells and potentially dependent on their cellular origin and/or injury context.
This project will generate extensive, high quality datasets to 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:** 10556676
- **Project number:** 1R01HL162629-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Maurizio Chioccioli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $436,350
- **Award type:** 1
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10556676

## Citation

> US National Institutes of Health, RePORTER application 10556676, Defining the cellular dynamics that orchestrate alveolar epithelial cell repair behaviors in live mammal (1R01HL162629-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10556676. Licensed CC0.

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