Grant Award Summary

The University of Washington received a $427,625 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), effective July 5, 2026 through March 31, 2031. This award supports fundamental research investigating the molecular mechanisms by which membrane-tethered E3 ubiquitin ligases regulate cell-surface receptor abundance and signaling sensitivity. The research employs a multidisciplinary approach integrating mass spectrometry, biochemistry, cell biology, and mouse models to systematically define substrate networks and functional mechanisms of these ligases, with the goal of uncovering fundamental principles governing receptor ubiquitination.

The project addresses two core scientific questions: (1) identifying the fundamental principles by which membrane-tethered E3 ligases recognize and target surface receptors, and (2) developing protein design strategies to modulate ligase activity or redirect them to new substrates for creating a programmable platform for surface-protein degradation. The research outcomes are intended to advance understanding of cell-to-cell communication regulation essential for embryonic development, tissue regeneration, and adult tissue homeostasis, while establishing foundations for potential therapeutic applications targeting surface-protein degradation pathways.