Introduction
GPCR signaling is increasingly understood as a spatially organized process, where receptors continue to signal from endosomal compartments after internalization and where the duration and location of signaling shape physiological outcomes.
The parathyroid hormone receptor (PTH1R) is a tractable model for these principles: a class B GPCR activated by two endogenous ligands, PTH and PTHrP, that generate distinct signaling patterns through differences in ligand-receptor complex stability, β-arrestin recruitment, and receptor trafficking.
This Masterclass uses rare PTH1R-associated disorders, including Jansen's metaphyseal chondrodysplasia, Blomstrand chondrodysplasia, and Eiken syndrome, as mechanistic case studies showing how altered receptor regulation produces distinct skeletal and renal phenotypes. It is intended for GPCR scientists, pharmacologists, and drug discovery professionals working on receptor trafficking, spatial signaling, and endocrine receptor biology.
Instructor
Dr. Jakob Höppner studies the spatial and ligand-dependent signaling of the parathyroid hormone receptor (PTH1R) as a model for understanding GPCR function. His work centers on compartmentalized receptor signaling and on rare skeletal and mineral-ion disorders, including Eiken syndrome and Jansen's metaphyseal chondrodysplasia, integrating cell-based biosensor assays, mouse genetics, and structure-guided ligand design to connect receptor mechanism with physiology and therapy.
He is a research fellow in the Endocrine Unit at Massachusetts General Hospital and Harvard Medical School, where he works with Thomas J. Gardella and Harald Jüppner. His research on disease-informed PTH1R biology directly shapes the focus of this Masterclass, where rare disorders serve as a window into the principles governing subcellular GPCR regulation.
