How STING immune signals are turned on and off
Factors regulating strength and duration of STING signaling
['FUNDING_R01'] · BROAD INSTITUTE, INC. · NIH-11166388
Researchers are identifying the genes and pathways that control how long and how strongly STING-driven inflammation lasts to help people with Aicardi-Goutières syndrome, SAVI, and related conditions.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | BROAD INSTITUTE, INC. (nih funded) |
| Locations | 1 site (CAMBRIDGE, UNITED STATES) |
| Trial ID | NIH-11166388 on ClinicalTrials.gov |
What this research studies
This project uses large-scale CRISPR genetic 'knockout' screens in cells and protein-mapping techniques to find the genes that control where STING moves inside cells and how it gets broken down. The team has already found that the ESCRT pathway recognizes ubiquitinated STING on endosomes and helps package it for degradation, and they are following up to see how disease-linked mutations keep STING chronically active. Work combines genome-wide screens, proximity proteomics, and focused genetic tests to track STING trafficking, autophagy, and signaling. The goal is to pinpoint molecular steps that could be targeted to stop harmful, long-lasting STING-driven inflammation.
Who could benefit from this research
Good fit: Patients with Aicardi-Goutières syndrome, SAVI, known TREX1 or STING pathway mutations, or other genetic interferonopathies would be most relevant for related future studies or sample donation.
Not a fit: People whose diseases are not driven by STING or chronic interferon signaling, or those needing immediate clinical treatment, are unlikely to benefit directly from this lab-focused project.
Why it matters
Potential benefit: If successful, this work could reveal drug targets or diagnostic markers to reduce harmful STING-driven inflammation in AGS, SAVI, and similar interferon-driven disorders.
How similar studies have performed: Previous genetic and proteomic studies have linked TREX1 loss and activating STING mutations to interferonopathies and the methods are well-established, but identifying ESCRT-dependent degradation as a regulator of STING is a relatively new finding.
Where this research is happening
CAMBRIDGE, UNITED STATES
- BROAD INSTITUTE, INC. — CAMBRIDGE, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: HACOHEN, NIR — BROAD INSTITUTE, INC.
- Study coordinator: HACOHEN, NIR
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions: Aicardi Goutieres syndrome