Targeting abnormal Gαs signaling in myeloid blood cancers
Official title: Mechanisms and targeting of aberrant Gas activation in myeloid neoplasms
Funded at Icahn School of Medicine at Mount Sinai · NIH-11313828 · Data updated 2026-11-12
Researchers are developing ways to block harmful Gαs signaling in people with myelodysplastic syndromes and related acute myeloid leukemias linked to splicing-factor mutations.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Icahn School of Medicine at Mount Sinai NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project start | April 1, 2023 |
| Project end | March 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $677,959 |
| NIH project number | 5R01CA271418-04 |
| Project ID | NIH-11313828 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates would be people diagnosed with myelodysplastic syndromes or acute myeloid leukemia whose cancer carries SRSF2 or U2AF1 splicing-factor mutations.
✕Less likely to help
Patients without splicing-factor mutations (SRSF2/U2AF1) or with unrelated leukemia subtypes are unlikely to benefit from therapies specifically targeting Gαs-L.
What this research studies
This project uses human induced pluripotent stem cell models with common splicing-factor mutations (SRSF2 and U2AF1) created by CRISPR to mimic patient disease. Scientists analyze RNA and protein to find mis-splicing of the GNAS gene that produces a longer, overactive Gαs protein isoform (Gαs-L). They will test strategies to inhibit this abnormal Gαs-L signaling in lab models to see if normal blood cell development can be restored. The work aims to translate these findings into candidate drug approaches for patients with SF-mutant MDS/AML.
Why it matters
Potential benefit: If successful, this work could lead to targeted treatments that block abnormal Gαs signaling and slow or prevent progression from MDS to AML for patients with these splicing-factor mutations.
How similar studies have gone: Broad splicing-modulator drugs have shown limited success in clinical testing, and targeting Gαs-L in SF-mutant myeloid neoplasms is a new, primarily preclinical approach.
Where this research is happening
-
Icahn School of Medicine at Mount Sinai
New York, United States Active
Researchers
- Principal investigator: Papapetrou, Eirini — Icahn School of Medicine at Mount Sinai
- Study coordinator: Papapetrou, Eirini
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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.