Molecular Etiology of Enchondromatosis

The project will study what regulates glycogen in the growth plate, enchondromas (ECA), and chondrosarcomas (CSA), and determine the function of glycogen in these growth plate and neoplastic chondrocytes. This includes prioritizing genes known to regulate glycogen that are differentially regulated in the growth plate and by IDH mutations, with a specific focus on Protein phosphatase 1 regulatory subunit 3C (PPP1R3C) and its regulation by Sterol regulatory-element binding proteins (SREBP). The research will define the function of glycogen and PPP1R3C using cell lines from human tumors and genetically modified mice that develop enchondromas. Additionally, the study will explore how SREBP regulates PPP1R3C and glycogen, and will involve genetic deletion of glycogen synthase or pharmacological inhibition of glycogen synthesis and breakdown.