# Understanding Mechanisms Underlying Chronic Stress-Induced Asthma in Children by Population and Single-Cell Epigenomics Approaches

> **NIH NIH R01** · CHILDREN'S MERCY HOSP (KANSAS CITY, MO) · 2021 · $643,818

## Abstract

SUMMARY
Asthma is a severe long-term disease of the lungs affecting millions of children in the US. An infection by
Rhinovirus (RV) is the most common trigger of an asthma attack which can be life threating for children with a
pre-existing condition. There are significant racial and ethnic disparities in asthma-related conditions where
African American and Hispanic children are more likely to have a diagnosis of asthma and significantly higher
asthma-related morbidity in comparisons with non-Hispanic white children. Genetic factors alone or in
combination with differences in environment exposures or lifestyle are important but have not been able to fully
explain observed disparities. Social environment such as chronic stressors experienced by racial and ethnic
minority groups have been linked to increased susceptibility to infection and chronic illness including asthma.
We hypothesize that social disadvantages during childhood result in long-lasting epigenetic alterations in key
regulatory regions impacting immune cell gene function that negatively impacts antiviral defense and
subsequently increase the risk of asthma. Our goal is to combine population-based epigenome mapping in nasal
mucosa with single immune cell analysis in large pediatric asthma cohorts of African American children with
detailed information about asthma and viral status as well as chronic stress exposures of several domains. In
Aim 1, we will implement an epigenome enrichment assay using our Methylation Capture Sequencing approach
to query the complete functional methylome in nasal mucosa (estimated to cover ~3M dynamic CpGs) derived
from thousands of children. We will deploy the approach in well-characterized pediatric cohorts to explore
predictive power of nasal epigenome signatures to capture chronic stress, viral infection along with asthma
phenotypes. In Aim 2, we will profile the immune cell landscape by high-throughput transcriptomic and
epigenome assays at single-cell resolution in hundreds of children with asthma. We will focus our single-cell
profiling efforts in blood derived from RV infected children that are exposed to high vs. low levels of chronic
stress to characterize immune cell signaling and viral response mechanisms epigenetically altered as a
consequence of social experiences. In Aim 3, we will perform in vitro validations of RV response in primary
macrophages differentiated from circulating monocytes from children that are discordant for chronic stress
exposure. We will perform detailed single-cell transcriptome and epigenome mapping before and after in vitro
infection with RV which will allow us to quantify the effects of social disadvantages on immune gene expression
at baseline and in response to RV infection.
Overall, our program will provide new insight into how genes and the social environment combine to influence
heterogeneity in the response to environmental stressors and contribute to the health disparity seen in children
with asthma.

## Key facts

- **NIH application ID:** 10247824
- **Project number:** 5R01MD015409-02
- **Recipient organization:** CHILDREN'S MERCY HOSP (KANSAS CITY, MO)
- **Principal Investigator:** Elin Grundberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $643,818
- **Award type:** 5
- **Project period:** 2020-08-26 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247824

## Citation

> US National Institutes of Health, RePORTER application 10247824, Understanding Mechanisms Underlying Chronic Stress-Induced Asthma in Children by Population and Single-Cell Epigenomics Approaches (5R01MD015409-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10247824. Licensed CC0.

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