# Understanding the Molecular Genetic Mechanisms of Asthma Risk Loci: IL33, IL1RL1, and GSDMB

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $600,961

## Abstract

PROJECT SUMMARY
In this new R01 application entitled “Understanding the Molecular Genetic Mechanisms of Asthma Risk Loci:
IL33, IL1RL1, and GSDMB,” the overarching hypothesis is that common genetic polymorphisms alter the
airway responses to environmental cues thus influencing the risk of type 2 inflammation in asthma.
The investigators address the limitations of traditional genetic epidemiological studies in identifying how
heritable risk loci influence the development of disease. They suggest that common genetic variants interact to
increase the risk of type 2 inflammation, the dominant pathology present in the airway of asthmatics. The
investigators have developed methods to characterize the degree of type 2 inflammation present in the airways
of asthmatics and use these measures to classify subjects as type 2 high or low for the purposes of defining
the genetic contribution to molecular disease endotypes. This application proposes in three aims to: 1) identify
the causal genetic variants that are associated with asthma in the IL1RL1 gene using CRISPR-Cas9 DNA
deletion, 2) to explore the cell biology of IL-33 release and the role of gasdermin proteins in this cellular
process, and 3) to explore the expression genetics of IL33 and GSDMB in airway epithelial cells in order to
fine-map the observed “expression quantitative trait loci” and relate these SNPs to risk of type 2 high asthma.
Together these studies will serve to 1) further define the genetic risk polymorphisms that influence the
development of type 2 high asthma, 2) will elucidate novel pathways for therapeutic intervention, and 3) to
define genetically the target population most likely to benefit from novel therapeutics.

## Key facts

- **NIH application ID:** 10075877
- **Project number:** 5R01AI136962-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Erin D. Gordon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $600,961
- **Award type:** 5
- **Project period:** 2018-01-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10075877

## Citation

> US National Institutes of Health, RePORTER application 10075877, Understanding the Molecular Genetic Mechanisms of Asthma Risk Loci: IL33, IL1RL1, and GSDMB (5R01AI136962-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10075877. Licensed CC0.

---

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