Small molecules to correct TRIO protein function linked to autism
Identification and characterization of chemical probes of TRIO GEF1 activity
This project looks for drug-like molecules that can increase or decrease activity of the TRIO protein, which is linked to autism and related neurodevelopmental conditions.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Yale University NIH-funded |
| Lab location | 1 site (New Haven, United States) |
| Project ID | NIH-11225126 on NIH RePORTER |
What this research studies
Researchers will build a lab version of the TRIO protein that includes the natural regulatory pieces and use it to screen many small molecules to find ones that boost or block TRIO GEF1 activity. They will run high-throughput biochemical assays to pick promising hits, then test and validate those compounds in cellular and neuronal models to see how they change TRIO-driven signaling. The team will use those chemical probes to learn how altered TRIO activity affects neuron development and to point toward possible therapeutic strategies for neurodevelopmental disorders.
Who could benefit from this research
Good fit: People with autism or related neurodevelopmental disorders who carry disruptive TRIO gene variants would be the most relevant group for future therapies arising from this work.
Not a fit: Patients whose condition is not related to TRIO gene dysfunction are unlikely to benefit directly from these specific TRIO-targeting probes.
Why it matters
Potential benefit: If successful, this work could produce research tools or early drug leads that help correct TRIO-related molecular problems and guide new treatments for some forms of autism and other neurodevelopmental disorders.
How similar studies have performed: Modulating GEF proteins with small molecules is relatively new, and TRIO GEF1-targeting probes are largely novel though similar biochemical screening approaches have yielded useful probes for other proteins.
Where this research is happening
New Haven, United States
- Yale University — New Haven, United States (Active)
Researchers
- Principal investigator: Koleske, Anthony J — Yale University
- Study coordinator: Koleske, Anthony J
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.