# Airway Basal Progenitor Dysfunction in the Detection, Progression and Pathogenesis of Early COPD

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $704,544

## Abstract

Project Summary
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic respiratory symptoms, poor
quality of life and death for millions of people in the US and worldwide. In vulnerable people, exposure to
cigarette smoke over 2-3 decades leads to fixed, expiratory airflow obstruction, the sine qua non of COPD.
Although 30-40% of smokers will eventually develop COPD, there are no clinical, physiologic, biologic or
molecular measures that identify vulnerable people during the earliest phase of disease, i.e. before COPD can
be diagnosed by impaired lung function (Early COPD). This inability to identify vulnerable people during early
COPD drastically limits the ability of physicians to alter its course. This proposal will address this key research
gap and meet a major goal of the COPD National Action Plan, by studying the role of airway basal progenitor
dysfunction in detection, progression and pathogenesis of early COPD. Airway basal progenitor cells are
essential for lung health and repair. By virtue of their ability to replicate (self-renewal) and differentiate into all
cell types present in the epithelium (multipotentiality), airway progenitors can return an injured epithelium to
normal structure and function. Preliminary data from older (~60 years old) people showed that bronchial and
sinonasal basal progenitor function is reduced in smokers with COPD, smokers with low-normal lung function,
and in younger smokers (~40 years old) without known lung disease. These findings imply that progenitor
function has an important role in disease pathogenesis. Experiments using bulk and single cell RNA
sequencing, metabolomics, and Seahorse measurement of glycolytic flux and mitochondrial respiration
identified a strong signal for altered energy metabolism as a prime driver of progenitor dysfunction in older
smokers with COPD or low-normal lung function, and in younger smokers with low progenitor self-renewal.
Therefore, we hypothesize that sinonasal and bronchial progenitor dysfunction a marker for early and
accelerated progression of COPD, and that progenitor dysfunction during early COPD is associated with
altered cellular bio-energetics. We will test this hypothesis in 70 younger (age 30-50 years) smokers without
known lung disease stratified by progenitor self-renewal for high and low progenitor function. An additional 20
never smokers without known lung disease and 20 smokers with COPD will be enrolled as controls. Aim 1 will
use a cross-sectional design to determine whether bronchial and sinonasal progenitor dysfunction are markers
of early COPD. Aim 2 will use a longitudinal design to determine whether bronchial and sinonasal progenitor
dysfunction are markers for disease progression during early COPD. Aim 3 will determine whether bronchial
and sinonasal progenitor dysfunction are associated with altered cellular bioenergetics. Successful completion
of these aims could have a game-changing impact by focusing efforts on disease prev...

## Key facts

- **NIH application ID:** 10737267
- **Project number:** 1R01HL164555-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Moumita Ghosh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $704,544
- **Award type:** 1
- **Project period:** 2023-08-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10737267

## Citation

> US National Institutes of Health, RePORTER application 10737267, Airway Basal Progenitor Dysfunction in the Detection, Progression and Pathogenesis of Early COPD (1R01HL164555-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10737267. Licensed CC0.

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