How the PACS2 E209K change affects brain cell energy and signaling
Impact of the E209K PACS2 Syndrome mutation on neuronal metabolism and neurotransmission.
Looks at how the PACS2 E209K mutation changes brain cell energy use and calcium signaling in people with PACS2 syndrome (DEE66) to point toward new treatment ideas.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Pittsburgh at Pittsburgh NIH-funded |
| Lab location | 1 site (Pittsburgh, United States) |
| Project ID | NIH-11318926 on NIH RePORTER |
What this research studies
This project studies the PACS2 E209K mutation found in people with PACS2 syndrome, a condition linked to seizures, developmental delay, low muscle tone, and autism. Researchers will use patient-derived cells and a mouse model that carry the same mutation to image ER–mitochondria contacts, track calcium signals, and measure changes in cellular metabolism. They will combine advanced microscopy and molecular methods to see how altered calcium handling shifts cells toward aerobic glycolysis and affects neuronal communication. The team will also explore ways to restore normal signaling and metabolism in cells and mice to guide possible future therapies.
Who could benefit from this research
Good fit: People diagnosed with PACS2 syndrome carrying the PACS2 p.Glu209Lys (E209K) mutation, including those with DEE66 features such as neonatal seizures, developmental delay, hypotonia, or autism, would be the primary candidates.
Not a fit: People who do not carry the PACS2 E209K mutation or whose neurological symptoms have other causes are unlikely to benefit directly from this research.
Why it matters
Potential benefit: If successful, this work could identify biological steps that can be targeted to reduce seizures and developmental problems in people with PACS2 syndrome.
How similar studies have performed: Preliminary lab work in patient cells and Pacs2E209K/+ mice already shows altered metabolism and reduced ER–mitochondria contacts, but targeted treatments for this mutation are novel and have not yet been tested in people.
Where this research is happening
Pittsburgh, United States
- University of Pittsburgh at Pittsburgh — Pittsburgh, United States (Active)
Researchers
- Principal investigator: Thomas, Gary — University of Pittsburgh at Pittsburgh
- Study coordinator: Thomas, Gary
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.