Federal Project Grant Award Summary

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awarded The Washington University a $388,750 Project Grant (CFDA 93.847: Diabetes, Digestive, and Kidney Diseases Extramural Research) on April 23, 2026, for research on podocin structure and function in kidney disease. The grant funds a five-year research project (through March 31, 2031) to elucidate the molecular mechanisms underlying steroid-resistant nephrotic syndrome (SRNS), a devastating pediatric kidney disorder caused by mutations in the NPHS2 gene encoding podocin. The research employs advanced cryo-electron microscopy (cryo-EM) techniques to resolve podocin's full-length structure at near-atomic resolution and determine how disease-causing mutations disrupt protein oligomerization and membrane targeting.

Beyond structural characterization, the research deliverables include the development of therapeutic discovery strategies to identify and validate rescue agents that restore function to defective podocin variants. The project will produce high-content imaging assays, small-molecule stabilizers identified through DNA-encoded library screening, and de novo peptide designs targeting oligomerization interfaces. These research outputs are intended to bridge fundamental knowledge gaps regarding podocin's role in maintaining glomerular filtration barrier integrity and ultimately support the development of targeted therapeutic approaches for steroid-resistant nephrotic syndrome.