# Cellular and molecular mechanisms of alveolar repair

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $673,790

## Abstract

PROJECT SUMMARY
Death or chronic lung dysfunction from acute respiratory distress syndrome (ARDS) is a dreaded consequence
of acute injury to the alveolar gas exchange region of lung. Other than antibiotics for bacterial pneumonia and
in some cases anti-inflammatory medications like corticosteroids, there are no specific therapies beyond
supplementary oxygen and ventilatory support. Thus, there is an urgent need to better understand how acute
alveolar injury is repaired and in cases when this is insufficient, what are the reasons for the failure to recover
gas exchange function. Once the precise cellular and molecular regenerative and maladaptive alveolar
responses are identified, we can move on to rationally engineer novel and specific treatments to promote
repair. We have recently mapped at high resolution the alveolar regenerative response to alveolar epithelial
type I (AT1) cell ablation, which revealed several unexpected mechanisms. In addition to conventional AT2
stem cell proliferation, we identified two other regenerative mechanisms. The first was immediate
transdifferentiation of AT2 cells without prior proliferation, followed by mitosis of resident binucleated AT2
progenitors found in healthy lungs. We also identified pathological responses from repeated AT1 cell ablation
consisting of excessive AT2 stem cell proliferation with loss of surfactant function and impaired AT1 cell
differentiation. Here, we plan to flesh out the molecular and cellular regulation of these regenerative programs
and to determine their physiological impact on maintaining proper gas exchange by preventing capillary leak
and pulmonary edema. In summary, we will apply precise cell type ablation and injury with state-of-the-art
experimental approaches to clarify at high temporal resolution the cellular and molecular basis of alveolar
epithelial repair.

## Key facts

- **NIH application ID:** 10750085
- **Project number:** 1R01HL167410-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Tushar Jasubhai DESAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $673,790
- **Award type:** 1
- **Project period:** 2023-08-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10750085

## Citation

> US National Institutes of Health, RePORTER application 10750085, Cellular and molecular mechanisms of alveolar repair (1R01HL167410-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10750085. Licensed CC0.

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