Projects

Identify Key Mechanotransducers to Promote Musculoskeletal Tissue Repair

Osteoarthritis (OA) is a debilitating joint disease affecting >300 million people. Despite decades of research, no treatments are available to prevent OA progression after an initiating joint injury. The development of treatments is hindered by the knowledge gaps in joint tissue mechanobiology. Current research methods commonly investigate single tissues without the influence of tissue crosstalk. Additionally, mechanotransduction mechanisms across joint tissues are not known; nor is how mechanotransduction changes with disease and inflammation. By understanding how cells sense and respond to a range of mechanical inputs, we can use this understanding to target specific mechanotransduction pathways to promote tissue repair. This information will further our understanding of how injury and disease drive post-traumatic OA through the involvement of multiple tissues as seen clinically. We are interested in identifying how injury and inflammation alter mechanotransduction in musculoskeletal tissues and leveraging this information to promote tissue repair.

Engineer Biomaterials for Mechano-Targeted Therapies

Post-traumatic OA is driven by injury to individual tissues, such as the meniscus, that then develops into joint-scale degeneration. Meniscus injuries are highly prevalent with 850,000 surgeries performed annually in the US, and half of the patients will develop OA even after surgery. To prevent continued tissue and joint degeneration following injury, we aim to develop biomaterial-based therapies that target key mechanotransducers in post-traumatic OA by intervening immediately following injury to repair damaged tissue or once OA has developed with multiple joint tissues affected. Biomaterials will be developed for tissue repair and joint-scale regeneration based on the mechanisms of mechanotransduction in musculoskeletal tissues. These interventions will address the clinical need for regenerative therapies to treat OA at multiple disease stages.

Role of Systemic Factors and Mechanics on Spine Health and Repair

Lower back pain is the main cause of years lived with disability affecting over 600 million people across the globe, with intervertebral disc (IVD) damage accounting for up to 42% of lower back pain cases. Progress in developing IVD treatments has been hindered, in part, by a knowledge gap in the understanding of how mechanical forces in vivo and changes in systemic factors, including changes in vascularity and immune cell infiltration, influence IVD repair. Such an investigation requires longitudinal assessments of IVD repair in an intact organism that includes the influence of systemic factors on tissue healing. Our lab is developing an intravital imaging approach to visualize cell and matrix dynamics in the mouse IVD, expanding our ability to monitor tissue repair longitudinally and evaluate the role of systemic factors and mechanics on IVD health and disease.