# Epigenetic mechanisms of inflammatory memory propagation in human airway epithelia

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $577,695

## Abstract

PROJECT SUMMARY / ABSTRACT
 Asthma and chronic bronchitis are among the top causes of death and hospitalizations worldwide.
Chronic airway inflammation in asthma causes goblet cell metaplasia (GCM), mucus hypersecretion, and
airway plugging, resulting in respiratory failure and poor quality of life. The mechanism for acquisition and
persistence of chronic inflammation is not known. Current anti-inflammatory treatments for asthma can be
ineffective and are not curative; chronic GCM resumes upon treatment discontinuation. Therefore, there is
an urgent need to understand the mechanisms of chronic inflammation and GCM in asthma. Host genetics
and the environment both contribute to asthma; the environment contributes to asthma by inducing immune
and airway epithelial epigenetic memory. Basal stem cells in the airway epithelium may acquire epigenetic
changes and act as a memory reservoir; as cellular turnover in the lungs occurs, basal cells replenish the
epithelium and may propagate inflammatory memory, causing GCM. The importance of airway epithelial
epigenetic memory in chronic lung inflammation is an emerging area of research. The central hypothesis of
this proposal is that basal stem cells acquire IL-13-induced epigenetic changes and propagate inflammatory
memory as they mitotically replenish the epithelium causing GCM and abnormal epithelial function; we plan
to address the following aims: Specific Aim 1: Identify mechanisms of IL-13-induced memory in human
large and small airway epithelia basal cells using transcriptomic, epigenomic, and clonotype analysis; we
will determine the effect of IL-13-induced memory on GCM and function of airway epithelia. Specific Aim
2: Determine epigenetic inflammatory memory in asthmatic nasal airway basal cells obtained non-
invasively using nasal brushings and in vitro expansion; this will allow us to determine how memory
acquired by basal cells in asthma contribute to GCM, and whether inflammatory memory in asthma is IL-13-
driven. Specific Aim 3: Investigate whether epigenetic changes acquired by tracheobronchial airway
basal cells in vivo determine response to IL-13 in vitro leveraging a biobank of primary tracheobronchial
basal cells developed by the PI; we will determine the epigenetic, transcriptional and phenotypic memory of
epithelia highly susceptible to and epithelia resistant to IL-13-induced GCM. We will also determine whether
drugs targeting GCM revert epigenetic memory. With the completion of this proposal, we expect to have
identified A) novel mechanisms, B) treatment targets, and C) biomarkers and precision medicine strategies
in asthmatics and other chronic inflammatory lung diseases. This is a first step to enable curative asthma
treatments. We will further the NHLBI’s mission to “translate basic discoveries into clinical practice” and to
“enhance the health of all individuals so that they can live longer and more fulfilling lives.”

## Key facts

- **NIH application ID:** 10422173
- **Project number:** 1R01HL163024-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Alejandro Antonio Pezzulo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $577,695
- **Award type:** 1
- **Project period:** 2022-05-05 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10422173

## Citation

> US National Institutes of Health, RePORTER application 10422173, Epigenetic mechanisms of inflammatory memory propagation in human airway epithelia (1R01HL163024-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10422173. Licensed CC0.

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