Our research focuses on the study of bone and joint health in the context of genetic regulation, aging, and injury repair. We conduct Genome Wide Association Studies to identify genes involved in regulating the variable anabolic response of bone to intermittent parathyroid hormone (PTH), and to identify genes involved in the regulation of bone strength as well as genetic interactions with aging and dysbiosis of gut flora. These studies seek to elucidate new targets for the development of candidate drugs for treating bone disease, and to provide insight for clinical decisions in the treatment of osteoporosis. Additional research focuses on molecular mechanisms involved in fracture repair, and the role of changes in joint loading patterns leading to disruption of articular chondrocyte homeostasis and subsequent tissue degradation associated with osteoarthritis.
Although some diseases affecting bone are caused by recognized mutations in a single gene, phenotypes defining low bone mass and strength are complex polygenic traits. Many genes which regulate bone strength and matrix quality have not been identified. Likewise, individual response to the intended anabolic therapy provided by teriparatide (PTH:1-34) is highly variable, suggesting that response to PTH is also a heritable trait worthy of investigation via genetic studies to unravel the lack of response for some individuals. A primary focus of our current work is aimed to identify genetic loci and genes that are involved in the regulation of bone strength and matrix integrity (quality), as well as the response to PTH. We use genetically diverse outbred rodent populations and detailed, high-throughput phenotyping pipelines to generate data for high-resolution gene mapping studies using genome wide association.