Federal Project Grant Award Summary

The University of Washington received a $1.6M Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded June 15, 2026, with completion targeted for May 31, 2028. This grant funds large-scale experimental research and computational modeling to characterize how genetic variants in the Factor IX (FIX) gene affect coagulation protein secretion, carboxylation, activation, and disease pathology. The research directly addresses a critical clinical challenge: more than half of FIX variants detected during genetic sequencing for hemophilia B diagnosis remain classified as variants of uncertain significance (VUS) due to insufficient functional data, limiting their clinical utility for diagnosis, reproductive planning, and family testing.

The research employs the MULTISTEP platform—a novel high-throughput screening technology developed by the research team—to systematically interrogate the functional effects of FIX missense variants at scale. Building on prior success in re-interpreting approximately 60 percent of missense VUS through assessment of secretion and carboxylation functions, this project extends the platform to evaluate additional FIX functional domains implicated in variant pathogenicity. The deliverables include variant effect scores, functional characterization data, and re-interpretation frameworks designed to convert currently unclassified genetic variants into clinically actionable information, thereby improving diagnosis and clinical management of hemophilia B while advancing understanding of coagulation biology relevant to thrombotic and hemorrhagic disorders.