Federal Project Grant Award Summary

The National Cancer Institute (NCI) awarded a $137,631 Project Grant under the Cancer Research Manpower program (CFDA 93.398) to Sloan-Kettering Institute for Cancer Research, effective July 3, 2026, with a completion date of June 30, 2028. This award supports biomedical research training and investigation into the mechanisms by which somatic mutations in RNA splicing factor genes (U2AF1, SF3B1, and SRSF2) drive the development of myelodysplastic syndromes (MDS) and related clonal hematopoietic disorders. The research focuses on identifying and characterizing novel protein isoforms generated by splicing factor mutations that escape non-sense mediated decay and contribute to disease pathogenesis through both cell-intrinsic and immune-modulatory mechanisms.

The funded research utilizes high-throughput screening approaches, including DNA-barcoded open reading frame library screens in murine hematopoietic progenitors, to identify disease-relevant isoforms. A key objective involves elucidating how aberrant mis-splicing of genes such as SPPL2A (signal peptide peptidase-like 2A) impairs major histocompatibility complex class II antigen processing and drives myeloid expansion, particularly in cooperation with tumor suppressor mutations. The deliverables encompass scientific findings and training in cancer research methodologies aligned with the National Cancer Program's priorities for understanding cancer mechanisms and advancing therapeutic development.