# ADAR1 regulation of MDA5 in Autoimmunity and Antiviral Responses

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2020 · $30,649

## Abstract

Project Summary
Detection of nucleic acids and production of type I interferons (IFNs) are principal elements of antiviral defense,
but can cause autoimmune disease if activated by self nucleic acids instead of viruses. Loss of function mutations
in the human ADAR gene cause Aicardi-Goutières Syndrome (AGS), a rare and severe autoimmune disease
that resembles congenitally acquired viral infection. Our lab and others defined ADAR1 as an essential negative
regulator of an RNA-sensing pathway. In the absence of ADAR1 functionality, endogenous ADAR1 RNA
substrates accumulate within cells and trigger type I IFN production through the anti-viral MDA5/MAVS pathway,
highlighting the connection between innate antiviral responses and autoimmunity, with important implications for
the treatment of AGS and related diseases. Very little is known about the nature of the RNA that accumulates
within these cells and initiates the IFN response.
In Aim 1, we will combine molecular biology and genomic tools to confirm and extensively characterize the
ADAR1 substrates that activate MDA5. In Aim 2, we will use a novel mouse model of the most common ADAR
mutation in the human population to uncover what role this mutation plays in the development of autoimmune
disease, and how it affects MDA5 activation by endogenous and viral ligands.
Our long-term goals are twofold: to rigorously define the mechanisms of autoimmune disease with the hope of
developing new treatments and preventative measures to apply to AGS and related diseases, and to use this
model system to probe more general questions about connections between innate immune detection of nucleic
acids and antiviral responses. Together with the other elements of my training plan, this project will prepare me
for a career independently conducting patient-focused basic immunological research.

## Key facts

- **NIH application ID:** 9991607
- **Project number:** 5F31AR076186-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Megan Maurano
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,649
- **Award type:** 5
- **Project period:** 2019-07-15 → 2021-03-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991607

## Citation

> US National Institutes of Health, RePORTER application 9991607, ADAR1 regulation of MDA5 in Autoimmunity and Antiviral Responses (5F31AR076186-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9991607. Licensed CC0.

---

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