ABOUT
Research in our laboratory is focused on understanding cellular and molecular mechanisms that regulate physiological and pathological bone metabolism, skeletal and craniofacial bone development and diseases. In particular, we are interested in the following lines of research:
THE ROLES OF AUTOPHAGY IN SKELETAL AND CRANIOFACIAL BONE METABOLISM
Autophagy is a conserved lysosomal degradation pathway that is regulated by particular autophagy genes such as fip200 (FAK-family Interacting Protein of 200 kDa) and atg5 (autophagy-related 5). Mounting evidence supports the vital role of autophagy in bone health. Our previous work showed that ablation of either fip200 or atg5 in osteoblasts leads to osteopenia in mice. However, the molecular mechanisms by which autophagy regulates osteoblast bone formation are primarily unclear, creating a significant knowledge gap in understanding autophagy dysfunction-related bone diseases. Moreover, additional significant gaps lie in the need to understand the autophagy-specific contribution to bone health, mainly because autophagy genes have autophagy-independent functions. Our current effort is to determine the molecular mechanisms and signaling pathways by which autophagy regulates osteoblast metabolic wiring, function, and lineage commitment using a combination of molecular, cell biological and mouse genetic approaches.
THE REGULATION OF SKELETAL AND CRANIOFACIAL BONE DEVELOPMENT 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 and TSC2. Tuberous sclerosing bone dysplasia is characterized by osteosclerotic changes in skeletal and craniofacial bones. In this disease, hyperactivity of mTOR (mammalian target of rapamycin) signaling is implicated. Despite the high frequency of osseous manifestation (>66%) in TSC patients, it is unknown to what extent and how mTOR signaling regulates bone metabolism in vivo. We established the first craniofacial sclerotic bone lesion mouse model of Tuberous sclerosis and found that enhanced mTOR signaling in neural crest-derived cells can increase bone mass through enlargement of the osteoprogenitor pool, which likely explains the sclerotic bone lesion observed in Tuberous sclerosis patients. We are currently using various genetic mouse models to elucidate the mechanisms by which mTOR signaling regulates skeletal and craniofacial bone development.
