How a fat-like molecule controls a key enzyme linked to brain health and some cancers
Official title: Defining the role of phosphatidic acid as an allosteric regulator of mitochondrial glutaminase
Funded at Cold Spring Harbor Laboratory · NIH-11263686 · Data updated 2026-11-12
Researchers are looking at whether a natural fat-like molecule called phosphatidic acid controls an enzyme (glutaminase) that affects brain function, acid balance, and certain cancers.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Cold Spring Harbor Laboratory NIH-funded |
| Lab location | 1 site (Cold Spring Harbor, United States) |
| Project start | March 15, 2023 |
| Project end | January 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $393,600 |
| NIH project number | 5R01GM149957-04 |
| Project ID | NIH-11263686 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with cancers that rely on glutaminase activity or patients with inherited GLS mutations would be most relevant to this research.
✕Less likely to help
Patients whose conditions are unrelated to glutamine metabolism or whose diseases are driven by different pathways are unlikely to see direct benefit from this basic lab research.
What this research studies
The team will examine how phosphatidic acid binds to and changes the activity of mitochondrial glutaminase using purified proteins and biochemical tests. They will test effects in cell models from tissues that normally express this enzyme (brain, digestive tract, kidney) and may include patient-derived cancer cells. Structural and molecular assays will be used to map the binding site and show how this regulation alters sensitivity to existing glutaminase inhibitors. Results could help explain inherited GLS disorders and why some cancers become resistant to current drugs.
Why it matters
Potential benefit: If successful, this work could point to better ways to block or modulate glutaminase, leading to improved cancer treatments and new approaches for metabolic or neurological disorders.
How similar studies have gone: Selective glutaminase inhibitors have reached clinical trials but often face rapid resistance, so this mechanistic approach to enzyme regulation is relatively novel and aimed at overcoming those limits.
Where this research is happening
-
Cold Spring Harbor Laboratory
Cold Spring Harbor, United States Active
Researchers
- Principal investigator: Lukey, Michael — Cold Spring Harbor Laboratory
- Study coordinator: Lukey, Michael
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.