Differential control of NK cell growth and survival in people with genetic replisome problems
Official title: Differential regulation of cell cycle entry and apoptosis in cytolytic lymphocytes informed by primary immunodeficiency
Funded at Columbia University Health Sciences · NIH-11378703 · Data updated 2026-11-12
This grant looks at why natural killer (NK) cells—crucial for fighting infections and cancer—become defective when replisome genes are altered, with a focus on people who have related genetic conditions.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Columbia University Health Sciences NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project start | August 1, 2025 |
| Project end | July 31, 2030 |
| Funding year | 2026 |
| Award (this year) | $737,300 |
| NIH project number | 5R01AI189818-02 |
| Project ID | NIH-11378703 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients with genetic replisome variants causing NK cell deficiency or dysfunction, and healthy controls for comparison.
✕Less likely to help
Healthy individuals without replisome-related NK cell defects may not directly benefit beyond general scientific insights.
What this research studies
Researchers will study how NK cells respond to replication stress caused by mutations in replisome genes (like MCM4, MCM10, GINS1, and GINS4) and why these cells are more vulnerable than other immune cells. They will use patient-derived cells and stem-cell models to compare NK cell development and function to T cells, aiming to map the window when replication problems affect NK cells. The work includes biochemical and cellular assays to link replisome dysfunction to cell cycle delays, DNA damage, and apoptosis in NK cells. Findings could reveal why NK cells are selectively impaired and identify clues for therapies to restore their function.
Why it matters
Potential benefit: If successful, this work could guide new strategies to boost NK cell function in patients with these genetic defects, potentially improving viral control and cancer surveillance.
How similar studies have gone: Preliminary work using patient-derived cells suggests NK cells are uniquely sensitive to replisome impairment, supporting progression to more detailed studies.
Where this research is happening
-
Columbia University Health Sciences
New York, United States Active
Researchers
- Principal investigator: Mace, Emily Margaret — Columbia University Health Sciences
- Study coordinator: Mace, Emily Margaret
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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.