Federal Project Grant Award Summary

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awarded a Project Grant of $192,288 to The Washington University in St. Louis under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) effective April 1, 2026, with completion targeted for January 31, 2031. This five-year award supports Dr. Portales-Castillo's research to establish independence as an investigator specializing in parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R) signaling in patients with skeletal dysplasias, particularly Eiken Syndrome. The project delivers basic and translational biomedical research aimed at resolving a paradox in PTH1R signaling whereby the same receptor mutation produces gain-of-function effects for one ligand (PTHrP) while exhibiting loss-of-function for another (PTH).

The research involves detailed in vitro characterization of PTH1R mutants and utilizes a humanized mouse model of Eiken Syndrome to investigate mechanisms of receptor desensitization mediated by β-arrestin. The project directly advances the program's objectives to improve understanding of disease mechanisms and mechanisms underlying endocrine and metabolic disorders through fundamental and clinical studies on hormone signaling, receptor function, and hormonal regulation. Deliverables include scientific findings on PTH1R signaling mechanisms that may inform future therapeutic approaches for patients with skeletal dysplasias and related endocrine disorders.