# Airway epithelial cell gene regulation: new mechanisms and therapeutic strategies

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $969,000

## Abstract

PROJECT SUMMARY
The epithelium that lines the airway comprises a variety of specialized cell types that play essential roles in lung
health. Changes in the epithelium are prominent features of asthma and other common lung diseases. During
normal differentiation, dramatic changes in gene expression are required for the development of the unique
functional capabilities of the basal, secretory, and ciliated cell populations within the epithelium. Furthermore, in
airway disease, each cell type has distinctive gene expression changes in response to pathogenic cytokines.
Over the past two decades, we have used transgenic mouse modeling, human cell culture, and clinical studies
to identify molecular mechanisms that underlie changes in epithelial gene expression that contribute to airway
obstruction in asthma. Although we and others have gained tremendous insights from mouse models, our overall
goal of understanding the biology underlying asthma and other human airway diseases has increasingly led us
to focus on developing appropriate human experimental systems. In the past several years, we and our
collaborators have developed a set of powerful approaches including single cell RNA-seq, ChIP-seq, massively
parallel reporter assays, and CRISPR-mediated gene editing, to address mechanistic questions in primary
human airway epithelial cells. These approaches now enable us to perform potentially groundbreaking
experiments that give new insights into airway epithelial cell complexity, identify key regulators of gene
expression and epithelial cell function, and reveal how specific airway epithelial gene regulators contribute to
asthma and other airway diseases. Most disease-associated genetic variants are found in regulatory regions,
and our work has important implications for understanding genetic contributions to airway disease risk. We will
also work to apply insights about gene regulation to develop approaches for therapeutic reprogramming of the
epithelium to prevent, cure, or treat disease. The environment at UCSF provides access to creative collaborators,
cutting-edge technologies, and key clinical resources and affords outstanding opportunities for working with early
career investigators who will be well positioned to continue to move the field forward.

## Key facts

- **NIH application ID:** 10349455
- **Project number:** 5R35HL145235-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** David J Erle
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $969,000
- **Award type:** 5
- **Project period:** 2019-04-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10349455

## Citation

> US National Institutes of Health, RePORTER application 10349455, Airway epithelial cell gene regulation: new mechanisms and therapeutic strategies (5R35HL145235-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10349455. Licensed CC0.

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