Understanding how mTOR-related brain malformations cause epilepsy
Decoding the cellular and molecular mechanisms of epileptogenesis and disease progression in mTORopathies
The team looks at how abnormal mTOR signaling and the immune protein C3 change brain cells and circuits to cause seizures in children with drug-resistant epilepsy.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Michigan at Ann Arbor NIH-funded |
| Lab location | 1 site (Ann Arbor, United States) |
| Project ID | NIH-11124668 on NIH RePORTER |
What this research studies
This project combines experiments in animals with analysis of brain tissue removed during surgery to understand why mTOR-related malformations (mTORopathies) cause seizures. Researchers will use genetic tools, electrical recordings, transgenic models, and single-cell RNA sequencing to map how individual cells and circuits change over time. They are especially examining whether the immune protein complement C3 creates a toxic microenvironment that damages inhibitory neurons and promotes hyperexcitability. The work links molecular and cellular changes to the circuit problems that drive epilepsy in children with focal cortical dysplasia.
Who could benefit from this research
Good fit: Ideal candidates are children with drug-resistant focal epilepsy due to mTOR-related cortical malformations (such as focal cortical dysplasia type II) who are undergoing surgical resection or whose families are willing to donate resected tissue.
Not a fit: People with seizure disorders not caused by mTOR pathway malformations, those whose seizures are well controlled with medication, or patients not undergoing brain surgery are unlikely to directly benefit from this project.
Why it matters
Potential benefit: If successful, this work could point to new ways to prevent or reduce seizures in children with mTORopathies and guide development of targeted therapies.
How similar studies have performed: Previous studies have linked mTOR signaling to epilepsy and suggested complement activation may play a role, but combining human surgical tissue with advanced genetic and electrophysiological models is a relatively new, translational approach.
Where this research is happening
Ann Arbor, United States
- University of Michigan at Ann Arbor — Ann Arbor, United States (Active)
Researchers
- Principal investigator: Wang, Yu — University of Michigan at Ann Arbor
- Study coordinator: Wang, Yu
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.