Description of Research Expertise

Research Interests
The Long lab seeks to understand the fundamental mechanisms underlying both normal skeletal development and the pathophysiology of bone disorders.

Key Words
mesenchymal stem/progenitor cells, metabolic and epigenetic regulation, skeletal cell differentiation and function, diabetic osteopenia, skeletal aging, bone development and regeneration

Research Details
Skeletal diseases, ranging from congenital dysplasia to osteosarcoma to osteoarthritis and osteoporosis, take a significant toll on human health. The overarching goal of our research is to discover key steps in the molecular or metabolic regulation of skeletal cell differentiation or function, with the hope of uncovering therapeutic targets for treating the various skeletal diseases. Many of our studies have centered around the role and mechanism of key developmental signals such as Hh, Wnt, Notch and Bmp in regulating skeletal development and homeostasis. Through mouse genetic studies, we have defined specific functions of the developmental signals in bone and cartilage cell differentiation. Our molecular and biochemical studies have led to the discovery that the developmental signals alter cell fate and activity in part through reprograming of the cellular metabolism of major energy substrates. Recently, the lab has identified cell-intrinsic disruption of glucose metabolism as a pathogenic basis for osteoarthritis and diabetic osteopenia. In other projects, we combine single-cell sequencing technology with genetic lineage-tracing or functional studies to identify skeletal stem/progenitor cells in the mouse, and to examine their contribution to bone maintenance or pathology.

Rotation Projects
Metabolic and epigenetic reprogramming during cell differentiation
Functional dissection of metabolic pathways in the skeleton of genetically modified mice
Lineage tracing of skeletal stem/progenitor cells in vivo
Other projects open for discussion