Bioengineering and Biomechanics
Novel biomaterials are being developed to regenerate bone tissue at weight-bearing sites, to investigate molecular interactions between cancer cells and substrate stiffness, and to deliver tumor killing drugs with minimal side effects. Applying the principles of solid mechanics to the analysis of bones from genetic/transgenic mouse models and pre-clinical models of disease, regulators of bone quality are being investigated with the goal of identifying novel therapeutic targets to increase fracture resistance. Also, matrix-sensitive technologies are being advanced toward improved clinical assessment of fracture risk.
Bone Development and Remodeling
Studies of skeletal development in fish and rodents are used to discover key regulators of bone and cartilage formation. The phenotypes created by genetic disruption of these pathways can then be used as functional biological readouts in high throughput drug screening. After development, the processes of coupled bone formation and resorption, collectively called remodeling, maintain skeletal health by replacing damaged bone. Imbalances in remodeling due to hormonal dysregulation and disuse are studied to uncover potential new targets for treating osteoporosis.
Cancer-Induced Bone Disease
Tumor interactions with the physical bone microenvironment, immune and stromal cells, and the signaling pathways that regulate these interactions, are explored to uncover novel therapeutic targets and windows. Tumor dormancy in bone and the cellular processes and signaling mechanisms that govern tumor cell quiescence are modeled in vivo and in vitro in the context of the bone microenvironment.
Endocrinology, Rheumatology, and Clinical Evaluations
Adult and pediatric projects enrolling patients in clinical registries, patient centered outcomes research, translational research and participation in multi-centered pharmaceutical trials for osteoporosis and metabolic bone disease; developing novel fracture prediction tools such as MRI measurement techniques.
Fracture Repair and Osteoporosis
The biological mechanisms of fracture repair and bone loss are being studied in order to prevent delayed unions or non-unions and to prevent fractures among the elderly. This involves improving our understanding of how aging, menopause, and diseases such as diabetes affect vascular invasion of the fracture callus and affect the balance between bone resorption and bone formation.
Genetics and Bone Disease
Large patient DNA repositories linked to de-identified patient records, such as BioVU, are used for Phenome Wide Association Studies (PheWAS) to identify novel mutations that are associated with skeletal diseases. These studies are leading to the identification of new genetic skeletal disorders and the re-purposing of existing drugs for specific genetically-driven diseases.
Infection and Bone
Osteomyelitis is a common and debilitating infectious disease of bone that is most commonly caused by bacterial pathogens. The mechanisms by which bacteria infiltrate, survive within, and ultimately trigger destruction of bone are active areas of investigation, as are new drug delivery strategies for the treatment of bone infection and contaminated fractures. Additionally, how skeletal cells sense and respond to microbes and cross-talk with the immune system are currently being determined using a combination of in vitro and in vivo model systems.