# MicroRNA directed pathway discovery in allergy and asthma

> **NIH HL R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2026 · $485,353

## Abstract

PROJECT SUMMARY
 Asthma is a highly prevalent chronic inflammatory airway disease that is genetically and
mechanistically linked to allergy and dysregulated cytokine-mediated communication between the
airway epithelial barrier and tissue-infiltrating immune cells. Th2 responses, insufficiently checked by
Tregs, drive chronic allergic inflammation through the release of cytokines that signal through STAT6.
Discovering novel regulatory circuits that control this process is a research opportunity with high
promise for therapeutic application. In the proposed research, we will investigate RNA circuits that
regulate Treg function and the pathobiology of allergy and asthma. Strong preliminary data implicate
specific microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and mRNA cis-regulatory
sequences as nodes in critical circuits that impact asthma incidence and pathogenesis.
 The proposed work is organized into 2 scientific aims. Aim 1 focuses on a circuit composed of the
abundant miRNA family miR-15/16, its large network of target mRNAs, and the lncRNA MALAT1.
miR-15/16 is required in Tregs to safeguard their suppressive function and inhibit allergic lung
inflammation. We will functionally characterize the empirically determined target network of miR-15/16
in Tregs, and investigate the role of miR-15/16 interaction with MALAT1. Both miR-15/16 and Malat1
are extremely abundant in T cells, and their physical interaction prevents miR-15/16 from fully
suppressing its coding gene targets. We will test the importance of this interaction in allergic lung
inflammation using novel transgenic mice with a precise CRISPR-mediated mutation in the miR-15/16
interaction site. Aim 2 probes the biological functions of noncoding mRNA sequences implicated in
asthma susceptibility by genetic studies, and implicated as cis-regulatory elements involved in RNA
regulation by their association with RNA binding proteins. This work is guided by GCLiPP, a
biochemical technique that we developed to 

## Key facts

- **NIH application ID:** 11323869
- **Project number:** 5R01HL109102-15
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Karl Mark Ansel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $485,353
- **Award type:** 5
- **Project period:** 2011-08-01T00:00:00 → 2029-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11323869

## Citation

> US National Institutes of Health, RePORTER application 11323869, MicroRNA directed pathway discovery in allergy and asthma (5R01HL109102-15). Retrieved via AI Analytics 2026-07-07 from https://api.ai-analytics.org/grant/nih/11323869. Licensed CC0.

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