Federal Grant Award Summary

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) awarded Massachusetts General Hospital a Project Grant of $585,012 effective June 2, 2026, through May 31, 2031, under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846). The research project investigates the role of the protein C10ORF10/DEPP1 in mediating skeletal muscle atrophy triggered by nutrient starvation or hypoxic conditions. The funded research will deliver scientific outputs including mechanistic findings on how DEPP1 functions as a transcriptional target of FOXO (Forkhead Box O) and HIF (Hypoxia Inducible Factor) transcription factors to activate autophagy and promote muscle loss, as well as preclinical animal model data and supporting ex vivo human skeletal muscle cell studies.

The research program consists of three coordinated aims designed to elucidate DEPP1's role in muscle homeostasis: characterization of DEPP1 function in skeletal muscle using novel genetically modified mouse models; definition of DEPP1's mitochondrial mechanisms both in vitro and in vivo; and testing of DEPP1's involvement in FOXO and HIF-mediated muscle atrophy models. Research outputs will include peer-reviewed publications, novel mouse model development, and mechanistic insights into a previously uncharacterized muscle atrophy pathway controlled by multiple upstream atrophy signals, advancing the understanding of musculoskeletal disease pathogenesis relevant to aging-associated muscle loss and disease-related atrophy conditions.