The Coleman laboratory is focused on translational research of treatments to prevent musculoskeletal disorders that result from injury, whether after a car crash or exposure to therapeutic doses of radiation during cancer treatment. Research revolves around the principle that mitochondria are the major drivers of oxidative stress in many cell types, including chondrocytes in articular cartilage. Blocking mitochondrial reactive species production through either inhibitors of mitochondrial metabolism or scavenging species with antioxidants after severe injury protects against posttraumatic osteoarthritis in all of operational animal models of orthopedic injury, including different species and different joints. The discovery of this pathway has led to ongoing clinical trials of treatments developed in Coleman lab projects. Current basic science projects describe oxidative stress in the context of a new multiscale model combining large animal intraarticular fracture, in vitro physical and mechanical testing, cell level mechanics modeled in silico, automated immunohistochemical scoring algorithms, and high precision, spatially-registered histological analyses. This model describes individual cell mechanics associated with the specific mitochondrial pathology under study.
This information can then be used to inform clinical decision making based on injury severity when using pharmacological interventions or deciding between comparable courses of surgical treatment. Within this framework, the Coleman lab also study the redox regulatory couple Nrf2-Bach-1, its status after these injuries, and the role of lipid peroxidation in the mitochondrial injury described. These viewpoints are also applied to injured joints after radiotherapy, which often fibrose causing great discomfort and diminished ability. Interrupting redox signaling during and after this injury could similarly represent a means to preventing arthrofibrosis.