Federal Project Grant Award Summary

The University of Pennsylvania received a $755,666 Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), effective March 15, 2026 through January 31, 2030. The research project, "Targeting Mitophagy Through PINK1 Splicing in MDS," will define a previously unrecognized mitochondrial surveillance mechanism essential for hematopoietic cell survival under mitochondrial stress and develop therapeutic strategies to treat myelodysplastic syndrome (MDS), a clonal hematopoietic disorder that impairs blood cell production and carries high risk of progression to acute myeloid leukemia.

The grant supports basic and translational research activities to elucidate how pathogenic mutations in splicing factors (SRSF2 and SF3B1) disrupt mitochondrial function and create cellular dependency on mitophagy—an organelle-specific autophagy pathway—and to identify therapeutic approaches targeting this pathway. Specifically, the research will investigate glycogen synthase kinase 3 (GSK-3) inhibition as a mechanism to block PINK1 splicing, impair mitophagy, and selectively eliminate MDS-mutant cells. The project also explores potential clinical applications of GSK-3 inhibitors in overcoming venetoclax resistance in patients with hematologic malignancies.