Project Grant R01DK144613

The National Institute of Diabetes and Digestive and Kidney Diseases awarded The Regents of the University of California, San Francisco $819,556 on August 27, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847).

The research investigates the molecular and cellular mechanisms underlying melanocortin-4 receptor (MC4R) activity-dependent trafficking and ciliary localization. MC4R is essential for body weight regulation and represents a pharmacological target for obesity treatment. The project combines cellular model studies with in vivo mouse studies to dissect the role of MC4R and MRAP2 ubiquitination in ciliary exit, characterize the roles of beta-arrestin and MC4R phosphorylation in regulated MC4R exit from primary cilia, and determine the nature of the ubiquitin ligase complex regulating MC4R exit from cilia. Primary cilia are cell surface projections that receive and transduce intercellular signals; the research builds on prior findings that MC4R localizes and functions at primary cilia and that MC4R and MRAP2 exit cilia upon activation.

Work is performed in San Francisco, California. The period of performance runs through June 30, 2031. The assistance type is a Project Grant, which supports basic and clinical biomedical research improving understanding of disease mechanisms and leading to improved prevention, diagnosis, and treatment.