# Mechanisms Controlling Expansion and Lineage Specification of Airway Progenitors in Development and Disease

> **NIH NIH R35** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $959,314

## Abstract

ABSTRACT
 End-stage lung diseases, such as chronic obstructive pulmonary disease
(COPD) and idiopathic pulmonary fibrosis (IPF) are devastating human conditions for
which there are no effective treatments. There is increasing evidence that the inability to
maintain epithelial integrity or recovery from sustained injury likely reflects a failure of the
stem cell compartment to mount an effective regenerative response. Tissue-specific
stem cells are crucial for homeostasis and integrity of adult organs. In the airway
epithelium these functions have been attributed largely to multipotent p63-dependent
basal cells. However, this role is shared by additional progenitors, particularly by a
sizable population of uncommitted p63-negative progenitors which occupy a parabasal
location interfacing both basal and luminal differentiating cells. Changes in the size or
function of the pool of uncommitted airway epithelial progenitors (basal, parabasal cells)
are often accompanied by disruption of the microarchitectural organization seen in
hyperplasias and metaplasias of end-stage lung conditions
 In spite of recent progress, there are still major gaps of knowledge on what
collectively the airway endogenous progenitors represent; their origin, diversity, and
contribution to plasticity in development, regeneration and disease states. Here we
propose to address these gaps of knowledge in our research program to: a) study the
molecular and cellular events that control the organization and behavior of the
stem cell compartment in the airways, and b) investigate the impact of the
disruption of these mechanisms in pulmonary disease pathogenesis. Results from
these studies will provide crucial insights currently lacking in the field about how tissue-
specific stem cells contribute to normal and disease processes in the lung.

## Key facts

- **NIH application ID:** 10085256
- **Project number:** 5R35HL135834-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Wellington V. Cardoso
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $959,314
- **Award type:** 5
- **Project period:** 2017-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085256

## Citation

> US National Institutes of Health, RePORTER application 10085256, Mechanisms Controlling Expansion and Lineage Specification of Airway Progenitors in Development and Disease (5R35HL135834-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10085256. Licensed CC0.

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