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Publications
All publications
An engineered insulin analog with dual insulin and IGF-1 receptor agonism and distinct signaling
Science Advances 12 (20): eaeb7558 (2026)
Insulin and insulin-like growth factors (IGF-1 and IGF-2) regulate metabolism, growth, and development via related receptors. In contexts such as brain function or fetal development, coordinated signaling by all three hormones is essential. We report the engineering of [GluB10, D-HisB24, GlyB31, TyrB32]-insulin (1Ins), an analog with high affinity for IR-A, IR-B, and especially IGF-1R. 1Ins binds IGF-1R ~1000-fold more strongly than native insulin, approaching IGF-1 levels. Cryo–electron microscopy structures reveal how minimal substitutions in 1Ins enable effective binding to both IR-A and IGF-1R. In neuronal cells, 1Ins robustly activates both IR and IGF-1R pathways, promotes survival, and \nexceeds native ligands in neuroprotective assays. In vivo, 1Ins regulates glucose effectively in mice and rats. Phosphoproteomic profiling confirms dual pathway activation and identifies targets specific to 1Ins. These findings demonstrate that rational design of dual-receptor agonists can yield…
Light-Driven Radical Catch-and-Release with BODIPY Photocages
Chemical Science 2026: Early View
Vesiculin reveals the role of the IGF2 C-domain in receptor specificity within the insulin–IGF system
Protein Science 35 (6): e70606 (2026)