# Omic Determinants of Longitudinal Lung Function in Asthma

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $771,762

## Abstract

PROJECT SUMMARY
Further characterization of longitudinal lung function (LLF) throughout adulthood in asthmatics is critically
important, as low lung function correlates with increased exacerbations, morbidity, and mortality. Precise
genomic and metabolomic profiling of the biological mechanisms underlying LLF trajectories will be
instrumental in understanding and ameliorating lung function deterioration. MicroRNAs (miRs; short non-coding
RNAs) exhibit broad impact on inflammatory cascades, leading to airway remodeling and chronic airway
obstruction, and specific metabolites provide a measure of real-time inflammatory changes that reflect both
genetic and environmental influences. Therefore, the combined use of miRs and metabolites has great
potential to provide critical insight into disease physiology and identify mechanisms to regulate, diagnose, and
prognosticate LLF. The objective of this proposal is to identify miRNA and metabolomic determinants of LLF
patterns, classified using longitudinal spirometry measures from electronic medical records (EMRs), that
accurately identify individuals with asthma at the greatest risk of progression to more serious chronic lung
obstruction. Our central hypothesis is that LLF trajectories are regulated by specific sets of genes, miRNAs,
and metabolites that can 1) inform on underlying biological dysregulation and 2) serve as biomarkers to
distinguish clinically actionable patterns of LLF, enabling personalized medicine approaches through the
identification of multiomic therapeutic targets. We will explore this hypothesis by generating the novel and
unique Biobank of Asthmatics with Longitudinal Lung Function (BALLF) cohort; which includes rigorous LLF
phenotyping generated from electronic medical records (Aim 1a) and global metabolomics profiling and
miRNA sequencing (Aim 1b) supplementing existing genetic and phenotypic data. We will identify metabolites
(Aim2a) and miRNAs (Aim2b) associated with these LLF; capitalizing on our rich preliminary data implicating
sphingolipid and eicosanoid biosynthesis to guide our analyses. Finally, we will leverage our extensive systems
biology expertise to integrate this multiomic data to improve our biological understanding of LLF (Aim3a) and
to develop clinically translatable biomarkers (Aim 3b). Crucially, we have the ability to both validate these
findings and to assess their generalizability in two existing independent cohorts of asthmatics. This will
represent the first integrative omic study of LLF trajectories in asthma focusing on the unique combination of
miRs, metabolites, and genes; as such the findings of this innovative proposal have tremendous potential to
elucidate the biological mechanisms of lung function decline and to influence the management of asthmatics at
risk of this devastating complication.

## Key facts

- **NIH application ID:** 10101236
- **Project number:** 1R01HL155742-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** JESSICA A LASKY-SU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $771,762
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101236

## Citation

> US National Institutes of Health, RePORTER application 10101236, Omic Determinants of Longitudinal Lung Function in Asthma (1R01HL155742-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10101236. Licensed CC0.

---

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