Metabolic regulation of skeletal development

The Wnt signal transduction pathway is required throughout skeletal development. Deregulation of this pathway causes a variety of skeletal diseases including both osteoporosis and high bone mass disease.  Recently, we identified glutamine metabolism as important regulator of osteoblast activity and bone formation in response to Wnt signaling.  We employ  genetic and cell culture techniques to understand the cellular and molecular mechanisms by which glutamine metabolism is regulated during skeletal development.  We are currently generating conditional mouse models to understand when and where glutamine metabolism is required during skeletal development

Identification of osteoanabolic therapies

Osteoporosis is a common disease characterized by significant decreases in bone mass affecting an estimated 9 million americans.  Decreased bone formation can result from too little bone formation or excessive bone resorption.  Current treatments focus almost exclusively on bone resorption due to a paucity of bone forming strategies for people with osteoporosis.  Our goal is to understand the molecular underpinnings of osteoblast activity and bone formation in order to rationally design therapies to increase bone formation.  We have generated a number of tools in the lab that allow us to screen small molecule libraries to identify compounds that increase osteoblast activity.  These compounds will be tested for efficacy in various mouse models of osteoporosis.