Federal Grant Award Summary

The University of Washington received a $654,536 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 April 15, 2026, through January 31, 2031. The award funds basic biomedical research investigating the pathogenic mechanisms of neutrophil elastase (NE) mutations in hereditary neutropenia, specifically severe congenital neutropenia (SCN) and cyclic neutropenia. The research employs isogenic, gene-targeted human induced pluripotent stem cells (iPSCs) to define the spatial and temporal determinants of NE pathogenicity and to elucidate how mutations disrupt proteolytic processing, trafficking, and catalytic activity during granulopoiesis.

This research addresses a critical gap in understanding disease mechanisms, as existing mouse models fail to recapitulate the human phenotype and current treatment options remain limited to hematopoietic stem cell transplantation. By utilizing human cell systems to investigate the disruption of spatial or temporal control of NE activity and testing suppressor mutations that modulate processing and catalytic function, the project aims to identify therapeutic targets and advance the scientific foundation for improved prevention and treatment of these life-threatening inherited blood disorders.