How 'jumping genes' and the cGAS–STING immune pathway may harm neurons in C9orf72 ALS/FTD
Role of the TE-cGAS-STING pathway in C9orf72-ALS/FTD pathogenesis
Looking at whether mobile DNA/RNA from 'jumping genes' triggers a cell immune sensor (cGAS–STING) and leads to neuron loss in people with C9orf72-related ALS or frontotemporal dementia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Thomas Jefferson University NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11194421 on NIH RePORTER |
What this research studies
Researchers will use patient-derived cells (iPSCs) and laboratory models to track how chromatin changes allow transposable elements (TEs) to become active. They will measure whether TE-derived RNA::DNA hybrids activate the cGAS/STING pathway and provoke inflammation and cell death, with a focus on the c-JUN/AP-1 and JNK signaling pathways. The team will compare cells carrying the C9orf72 mutation to control cells and test whether restoring autophagy or blocking the pathway reduces damage. Results will help identify molecular steps that could be targeted to protect neurons.
Who could benefit from this research
Good fit: Ideal candidates would be people with a confirmed C9orf72 repeat expansion who can provide clinical information or biological samples.
Not a fit: People without the C9orf72 mutation or with unrelated types of dementia are less likely to benefit directly from this work.
Why it matters
Potential benefit: Could reveal molecular targets to reduce harmful inflammation and protect neurons in people with C9orf72-linked ALS/FTD.
How similar studies have performed: Related work showed TE de-repression and cGAS/STING activation in Alzheimer’s patient-derived cells, but applying this pathway to C9orf72 ALS/FTD is a newer and less-tested direction.
Where this research is happening
Philadelphia, United States
- Thomas Jefferson University — Philadelphia, United States (Active)
Researchers
- Principal investigator: Trotti, Davide — Thomas Jefferson University
- Study coordinator: Trotti, Davide
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.