# Transcriptional Responses to Wildfire Pollution in Airway Epithelial Cells Identify Genetic Risk Factors and Mechanisms of Asthma Exacerbations

> **NIH NIH K08** · NATIONAL JEWISH HEALTH · 2023 · $173,448

## Abstract

Project Summary/Abstract
Increased levels of air pollution from wildfires are directly associated with asthma exacerbations but
the mechanisms mediating this association are not understood. Furthermore, the severity of asthma
symptoms that result from wildfire exposure vary considerably by individual. We seek to identify
Transcriptional Regulatory Elements (TREs) that connect wildfire particulate exposures with genetic
variants associated with asthma to identify susceptibility features and mechanisms that govern asthma
exacerbations.
We will employ wood smoke particle (WSP) exposure in primary airway epithelial cells cultured at air-
liquid interface to model the interaction between the respiratory epithelium and fine particulates
released by wildfires. We will assay chromatin accessibility and nascent transcription using next-
generation sequencing techniques to identify TREs regulated by WSP. Then, using a permutation-
based bioinformatic approach, we will intersect the genomic coordinates of these TREs with genomic
susceptibility loci for asthma. We will then characterize the transcriptional function of single nucleotide
polymorphisms (SNPs) that result from this intersection. We will test TRE function in the context of
WSP exposure with and without the SNPs in plasmid-derived luciferase reporters and in genomic
DNA, using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) – Cas9 tool to
introduce the variant alleles. Finally, to assay the physiologic significance of these TRE-SNP overlaps,
we will test the role of the rs258760 SNP, which inhabits a TRE under regulation by WSP and controls
expression of the glucocorticoid receptor, in mediating Interleukin-8 secretion by exposing airway
epithelial cells from donors with the major and minor alleles to WSP and dexamethasone.
This project will identify and characterize genomic features that connect air pollution with asthma
exacerbations. These loci and the genes they regulate will serve as candidates for pharmacologic
therapies to mitigate asthma symptoms associated with wildfire air pollution. Furthermore, this
project develops a method to integrate multiple models of disease in a genomic context. This
strategy may be used to propose novel treatments for asthma.

## Key facts

- **NIH application ID:** 10573003
- **Project number:** 1K08ES034820-01
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Arnav Gupta
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $173,448
- **Award type:** 1
- **Project period:** 2022-12-17 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10573003

## Citation

> US National Institutes of Health, RePORTER application 10573003, Transcriptional Responses to Wildfire Pollution in Airway Epithelial Cells Identify Genetic Risk Factors and Mechanisms of Asthma Exacerbations (1K08ES034820-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10573003. Licensed CC0.

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