# Identifying niche factors regulating distinct properties of AT2 stem cells

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $535,834

## Abstract

PROJECT SUMMARY
A number of serious respiratory diseases cause problems with gas exchange, which is the principal function of
the lungs. Some of these are sudden in onset, like lung injury from a severe pneumonia, while others develop
over long periods of time, like COPD and Idiopathic Pulmonary Fibrosis (IPF). There is some evidence that the
chronic forms of respiratory failure result from loss of the capacity of the lungs to maintain themselves, in part
due to dysfunction of resident lung stem cells that normally perform this role. Therefore, discovering the
specific molecular and cellular mechanisms by which lung stem cells are regulated throughout life may be
helpful for understanding how COPD and IPF develop. Achieving this deep level of understanding about lung
stem cell regulation may lead to improved strategies to predict, diagnose, and even pharmacologically treat
such diseases. Furthermore, given the easy accessibility of the lung via medical bronchoscopy, it is an ideal
organ to target with the delivery of healthy stem cells that might prevent disease progression or even produce
improvement if they can be successfully transplanted into diseased lungs. We have found that one of the
functional cells in the gas exchange region, the alveolar type II (AT2) cell, acts as a stem cell for mouse lung
throughout the lifespan, and identified several factors that regulate its activity. The AIMS of this proposal are to
expand our understanding of how these stem cells are regulated by studying the local environment that
provides the signals that control their activity, including proliferation and differentiation. We will investigate
three specific and distinct aspects of the stem cell behavior, including how it is induced to proliferate to
generate new cells, how it attains the capacity to transiently regulate itself in response to injury, and whether
the regulatory environment is as or more important than the stem cell itself for maintaining the lungs over the
lifespan. Our findings will significantly deepen our understanding of precisely how these lung stem cells can be
deliberately manipulated to generate large numbers suitable for cell transplantation, or by pharmacologically
driving their activity for therapeutic 're-growth' purposes.

## Key facts

- **NIH application ID:** 10178079
- **Project number:** 5R01HL142549-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Tushar Jasubhai DESAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $535,834
- **Award type:** 5
- **Project period:** 2018-08-22 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178079

## Citation

> US National Institutes of Health, RePORTER application 10178079, Identifying niche factors regulating distinct properties of AT2 stem cells (5R01HL142549-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10178079. Licensed CC0.

---

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