Long Laboratory

Bone disorders exact a considerable toll on human health in both children and adults. The Long Lab seeks to understand the fundamental mechanisms underlying both normal skeletal development and the pathophysiology of bone diseases.

Through mouse genetic studies, the Long Lab has defined specific functions of key developmental pathways such as Hedgehog, Wnt, and Notch signaling in bone development and homeostasis. Biochemical studies conducted in the lab have led to the discovery that developmental signals reprogram cellular metabolism to change cell fate.

Current research in the lab includes studies of skeletal stem cells and progenitors, metabolic regulation of skeletal cells, and the integration of bone and whole-body metabolism. The lab is testing the hypothesis that dysregulation of glucose metabolism is a root cause for skeletal disorders associated with diabetes and aging.

Project Highlights

• Bone metabolism in type I or type II diabetes animal models: Both juvenile and adult diabetes are associated with increased bone fractures. Current studies are uncovering the cellular and molecular basis for the bone frailty, with the goal of discovering new therapeutic targets.
• Skeletal aging: Osteoarthritis and osteoporosis are commonly related with aging, but current treatments are inadequate. Current projects in the Long Lab are exploring the connection between changes in cellular metabolism and skeletal health during aging.
• Skeletal stem and progenitor cells: The human skeleton is built and maintained by stem and progenitor cells but the identity, location, and control of those cells in the body remain incompletely understood. Ongoing projects aim to track and manipulate those cells genetically by using lineage-tracing techniques in animal models.
• Human bone diseases in a dish: Congenital bone diseases are devastating for children but in-depth studies are challenging due to the inaccessibility of sufficient bone cells. Current studies are underway in the Long Lab to direct patient skin cells to become bone cells in a dish where they can then be studied in detail.