# Understanding the Molecular Genetic Mechanisms of Asthma Risk Loci: IL33, IL1RL1, and GSDMB - COVID 19 Supplement

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $330,485

## Abstract

PROJECT SUMMARY:
This is an administrative supplement to the parent R01 “Understanding the Molecular Genetic Mechanisms of
Asthma Risk Loci: IL33, IL1RL1, and GSDMB,” which focuses on understanding how genetic polymorphisms
alter epithelial secretion of the IL-1 family cytokine, IL-33. This supplement entitled “Clash of Titans:
Understanding the Airway Epithelial Interferon and IL-1 Response to SARS-CoV-2 Infection,” addresses a
critical need during a global pandemic. Our hypothesis is that a key virulence factor in the SAR-CoV-2 virus,
the E protein, triggers IL-1B secretion from epithelial cells in a gasdermin and caspase dependent manner.
That IL-1 secretion acts in an autocrine fashion, to inhibit critical interferon responses that are required to
constrain the virus to the upper airway and prevent lower airway infection. The proposal allows our laboratory
to use genetically altered cell lines that we generated as part of the parent grant to quickly study the balance of
interferon and IL-1 responses of the airway epithelium to SARS-CoV-2 infection and test commercially
available drugs that block caspases or IL-1 signaling to inhibit viral replication. This proposal seeks to rapidly
translate our current understanding of airway epithelial cell biology to address a critical need for therapeutics
against the SARS-CoV-2 virus which has currently infected more than a million people worldwide and killed
over 60,000 in less than 4 months.

## Key facts

- **NIH application ID:** 10141887
- **Project number:** 3R01AI136962-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Erin D. Gordon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $330,485
- **Award type:** 3
- **Project period:** 2020-06-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141887

## Citation

> US National Institutes of Health, RePORTER application 10141887, Understanding the Molecular Genetic Mechanisms of Asthma Risk Loci: IL33, IL1RL1, and GSDMB - COVID 19 Supplement (3R01AI136962-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141887. Licensed CC0.

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