# Genomics and Pharmacogenomics of Symptoms in Asthma

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $680,342

## Abstract

ABSTRACT
Asthma affects over 300 million individuals worldwide. Uncontrolled asthma is associated with a
doubling of direct costs, missed workdays, and school absenteeism; up to 80% of asthma patients
may be uncontrolled with regard to asthma symptoms. Circulating microRNAs (miRNAs) are
stable intercellular communicators that function to regulate gene expression and can serve as
biomarkers for symptoms and disease. The overall objective of this study is to ascertain the role
of circulating miRNA and miRNA genetics in control of asthma symptoms. In this competitive
renewal proposal, “Genomics and Pharmacogenomics of Symptoms in Asthma”, we hypothesize
that circulating miRNAs are functionally associated with asthma treatment guidelines-
based symptoms control, symptomatic exacerbations, and symptoms response to
therapy. Asthma symptoms will be defined as well-controlled, poorly controlled, and uncontrolled
via Global Initiative for Asthma (GINA) guidelines and by frequency of severe exacerbations. The
relevant miRNAs will be identified via three specific aims. The first aim seeks to identify
differentially expressed miRNAs influencing asthma symptoms control through miRNA
sequencing of serum samples from multiple asthma cohorts totaling over 4000 subjects. Cross
sectional studies will identify miRNAs indicative of mechanistic differences between the controlled
and uncontrolled asthmatic, while pharmacogenomic and longitudinal studies will identify miRNAs
that provide biologic insights and may form the basis of a predictive biomarker test for
identification and treatment of the difficult to control asthmatic. The second aim evaluates the
role of miRNA genetics in asthma symptoms control through identification of polymorphisms that
affect miRNA expression (via allele specific expression) and those affecting miRNA biogenesis.
The salient variants will be identified via whole genome sequencing in over 3500 asthmatic
subjects and through whole genome imputed genome-wide association data in over 30,000
asthmatic subjects. The genetic variants will be associated with symptoms control and assessed
for ability to predict ongoing symptoms and drug treatment response. The final aim will
functionally link the miRNA and genetic variants, including miR-130a-3p and let-7b-5p, from Aims
1 and 2 with physiologic and inflammatory changes in human airway epithelial cells, using miRNA
mimics, miRNA inhibitors, and CRISPR-based gene editing. The success of this proposal will
yield novel understanding into the pathogenesis of asthma symptoms control and asthma
exacerbations and may provide direct future bedside clinical translation in the form of biomarkers
to enhance guidelines based therapeutic recommendations and/or miRNA based therapeutics.

## Key facts

- **NIH application ID:** 10868704
- **Project number:** 5R01HL162570-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** KELAN G TANTISIRA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $680,342
- **Award type:** 5
- **Project period:** 2011-09-27 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868704

## Citation

> US National Institutes of Health, RePORTER application 10868704, Genomics and Pharmacogenomics of Symptoms in Asthma (5R01HL162570-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10868704. Licensed CC0.

---

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