How loss of TDP-43 causes abnormal gene splicing in frontotemporal dementia
Cryptic exon splicing mediated by TDP-43 loss of function as the underlying mechanism of pathogenesis in FTLD-TDP
This project looks at how losing the protein TDP‑43 leads to abnormal 'cryptic' gene splicing in people with TDP‑43–related frontotemporal dementia to find early markers and targets.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Stanford University NIH-funded |
| Lab location | 1 site (Stanford, United States) |
| Project ID | NIH-11172547 on NIH RePORTER |
What this research studies
Researchers will combine human brain tissue, genetic data, high-resolution images, and lab models to track when and where TDP‑43 stops working and causes mis-splicing. The team will map cryptic splicing events across different brain regions and FTLD‑TDP subtypes as sensitive indicators of TDP‑43 activity. All data, images, and analysis code will be shared through an online portal so other scientists and clinicians can use the findings. The center brings genetics into the core of the work to speed discovery of biomarkers or therapy targets.
Who could benefit from this research
Good fit: People with frontotemporal dementia suspected to involve TDP‑43 pathology, family members interested in genetic contributions, or individuals willing to donate genetic data or brain tissue are the most relevant candidates.
Not a fit: People with dementias not related to TDP‑43 pathology or those unable to provide consent for genetic or tissue donation are less likely to directly benefit.
Why it matters
Potential benefit: If successful, this work could reveal early molecular markers of TDP‑43 dysfunction and point to new targets for diagnosis or treatment.
How similar studies have performed: Prior studies have linked TDP‑43 loss to mis-splicing and provided initial biomarker leads, but this integrated, large-scale center approach is a novel expansion of that work.
Where this research is happening
Stanford, United States
- Stanford University — Stanford, United States (Active)
Researchers
- Principal investigator: Gitler, Aaron D. — Stanford University
- Study coordinator: Gitler, Aaron D.
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.