# cGAS-mediated glial responses to DNA damage: A pilot study

> **NIH NIH R03** · UNIVERSITY OF NORTH CAROLINA CHARLOTTE · 2020 · $71,204

## Abstract

Abstract
Genomic instability is a major driving force for cancer and age-related diseases. While
DNA damage responses were long thought to regulate genome integrity and cell fates,
evidence is accumulating that genomic instability also triggers inflammatory responses.
Recent studies have provided insight into the mechanisms underlying such responses
with the demonstration that the cytosolic DNA sensor, cyclic GMP-AMP synthase
(cGAS), can play a key role in linking DNA damage to innate immunity. Interestingly, our
research team has recently described the ability of human microglia and astrocytes to
respond to foreign cytosolic double-stranded DNA and we demonstrated that human glia
show robust levels of cGAS protein expression at rest and following activation.
Furthermore, we showed these cell types constitutively express the critical downstream
cGAS adaptor protein, stimulator of interferon genes (STING). In this R03 pilot study,
we will begin to test the hypothesis that the cGAS-STING pathway detects cytoplasmic
DNA in microglia and/or astrocytes after genotoxic stress and initiates glial auto-
inflammatory responses. This project stems from a new collaboration between two
experienced investigators with complementary expertise in the study of DNA damage
repair mechanisms and glial innate immune sensor molecules. In these preliminary
studies, we will determine whether genomic DNA damage elicits micronuclei formation
and an elevation in the level of the cGAS product cGAMP in cultured glia, and we will
correlate such responses with the production of auto-inflammatory mediators or
potentially anti-tumor factors such as type I interferon. Furthermore, we will directly
assess the relative importance of the cGAS-STING pathway in glial responses to DNA
damage following pharmacological inhibition and/or CRISPR/cas9 genome editing. The
proposed pilot R03 studies are an important first step in this new research direction and
will provide a solid rationale for a more comprehensive investigation into the role of the
cGAS-STING pathway in CNS cellular senescence and cancer for which future R01
mechanism support will be sought.

## Key facts

- **NIH application ID:** 10019417
- **Project number:** 5R03NS111260-02
- **Recipient organization:** UNIVERSITY OF NORTH CAROLINA CHARLOTTE
- **Principal Investigator:** Christine A. Richardson
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $71,204
- **Award type:** 5
- **Project period:** 2019-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019417

## Citation

> US National Institutes of Health, RePORTER application 10019417, cGAS-mediated glial responses to DNA damage: A pilot study (5R03NS111260-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10019417. Licensed CC0.

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