# Determining the role of TP53 regulation in alveolar epithelial transitional cell state,  and the contribution of alveolar epithelial transitional cell state to pulmonary fibrosis

> **NIH NIH F31** · DUKE UNIVERSITY · 2024 · $48,974

## Abstract

ABSTRACT
 Respiratory disease is the third leading cause of death in the industrialized world. Pulmonary fibrosis
(PF) is a progressively debilitating and terminal disease in which the normally pliable tissue of the lung is
gradually replaced with rigid scar tissue. PF is an especially difficult respiratory disease, as there are no
effective treatments and patients die within an average of three to five years of diagnosis. Current models
suggest that alveolar injury and ineffective repair underlie the pathogenesis of PF and other lung diseases.
However, the mechanisms by which injury in the alveolar epithelium contributes to fibrotic disease remain
unclear. Single cell transcriptomics data demonstrate that a transitional state exists between the well
characterized alveolar type 2 (AT2) and type 1 (AT1) epithelial cells. Furthermore, marker analysis of this
transitional state in human PF lungs suggests that accumulation of transitional cells occurs in regions with
dense myofibroblasts in fibrotic lungs. It is unclear what molecular mechanisms regulate the state of alveolar
epithelial cells, but data from our lab has shown that TP53 is transiently upregulated in normal differentiation
of AT2 to AT1 cells. This proposal details approaches to uncover the role of TP53 in regulating alveolar
epithelial cell states, and to determine the impact of an alveolar epithelial transition state on pulmonary
fibrosis. Understanding the mechanisms that drive these transitional states and their potential role in PF
disease pathogenesis offers new avenues for developing novel therapies for fibrotic and other lung diseases.

## Key facts

- **NIH application ID:** 10819704
- **Project number:** 1F31HL172360-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jeremy Morowitz
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-03-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10819704

## Citation

> US National Institutes of Health, RePORTER application 10819704, Determining the role of TP53 regulation in alveolar epithelial transitional cell state,  and the contribution of alveolar epithelial transitional cell state to pulmonary fibrosis (1F31HL172360-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10819704. Licensed CC0.

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