The regulation of bone quantity and quality by mTOR signaling
Tuberous Sclerosis (TS) is a genetic disorder characterized by the presence of benign congenital tumors in multiple organs and is caused by mutations in one of two genes, called TSC1 (Tuberous Sclerosis Complex 1) and TSC2, which are negative regulators of mTOR signaling. We generated a TS mouse model and found that upregulation of mTORC1 signaling in neural crest derived cells led to increased craniofacial bone mass with increased TMD. In this project, we will: 1) characterize the craniofacial bone development abnormality caused by the dysregulated mTOR signaling in this mouse model; 2) determine the effect of dysregulated mTOR signaling on bone quality; 3) determine the mechanisms by which dysregulated mTOR signaling regulates bone quantity and quality.
Submitted grant proposal for $1,488,000 from the NIH
Tsc1 deletion increases craniofacial bone mass by increasing extracellular matrix (ECM) production and enhancing osteoblast differentiation
Presented at the 39th American Society of Bone and Mineral Research Annual Meeting, Denver, CO
Presented at the 38th American Society of Bone and Mineral Research Annual Meeting, Atlanta, GA
Tsc1 Regulates the Balance Between Osteoblast and Adipocyte Differentiation Through Autophagy/Notch1/Œ≤-Catenin Cascade
Published article in Journal of Bone and Mineral Research (JBMR).
Presentation in Atlanta, GA