# Genomic Analysis of Epithelial Growth and Repair Mechanisms in Aspirin Exacerbated Respiratory Disease

> **NIH NIH K23** · NATIONAL JEWISH HEALTH · 2021 · $31,862

## Abstract

Abstract/Project summary
Aspirin Exacerbated Respiratory Disease (AERD) is a relatively homogeneous disease characterized by adult-
onset severe asthma, development of non-cancerous growths in the nasal canal (i.e. nasal polyps) and aspirin
allergy. The cause of AERD is unknown, although likely results from environmental insults in combination with
genetic susceptibility. AERD disease homogeneity increases the possibility of discovering narrowly-defined
genetic contributors, and makes it an ideal population to study the genetic and epigenetic changes that cause
asthma. We recently discovered that gene expression of epithelial growth and repair (EGR) genes are
substantially decreased in bronchial airway epithelial cells of severe asthmatics compared to less severe
asthmatics and healthy controls. This new finding indicates that epithelial integrity and related processes may
be of primary importance to the development of severe asthma, and potentially the severe asthma subtype,
AERD. This finding was later supported in a subsequent lab model, which showed that blocking a central
epithelial repair and differentiation gene, human epidermal growth factor receptor 2 (ERBB2), decreased
healing time of bronchial epithelial cells after injury. Thus, the objective of the proposed study is to
determine whether EGR gene are also down-regulated in AERD, a homogeneous severe asthma
subtype. As an extension, we will also determine whether genetic mutations and/or epigenetic changes relate
to and potentially explain this down-regulation of EGR genes. Specifically, we plan to obtain gene expression
of freshly brushed nasal airway epithelial cells of 75 AERD patients and 35 healthy controls, noting that nasal
epithelial gene expression has recently been shown to mirror lung epithelial changes in asthmatic airways.
Swabbing the nasal canal for epithelial cells allows to evaluate airway epithelial cell gene expression non-
invasively. Our experimental design contrasts AERD gene expression profiles against healthy controls, and
determines whether EGR genes are depressed in AERD relative to health controls. As a corollary, we look to
discover an AERD-specific gene expression profile which may one-day aid in diagnosis and expand current
knowledge of disease mechanisms. As an extension, we will correlate gene expression changes, specifically
any finding of down-regulated EGR genes, with methylation changes (i.e. epigenetic changes) and genetic
mutations. This K23 funding will provide protected research time to become an independent physician
researcher. My prior and current training in statistics, bioinformatics, and gene expression analysis is
complemented by specialized clinical training in the care of severe asthma patients. Thus, I have a unique
clinical and computational expertise to perform the data analysis, and interpret and integrate genomic findings
in a clinical and biological context. I have chosen mentors that are leading experts in the fields of immunology...

## Key facts

- **NIH application ID:** 10129995
- **Project number:** 5K23HL144418-05
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Brian David Modena
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $31,862
- **Award type:** 5
- **Project period:** 2018-09-16 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129995

## Citation

> US National Institutes of Health, RePORTER application 10129995, Genomic Analysis of Epithelial Growth and Repair Mechanisms in Aspirin Exacerbated Respiratory Disease (5K23HL144418-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10129995. Licensed CC0.

---

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