My ultimate career goal is to become a successful independent investigator who can contribute significantly to the field of aging tendon mechanobiology. The objective of this proposal is to provide me with the remaining necessary research training in order to make the transition to independence effectively. To achieve this objective, a training regimen has been developed, consisting of research aims and substantial training activities. The proposed scientific studies will seek to develop a novel in vitro tendon injury model focused on age and compressive overload, in order to understand mechanistically the consequences of an increased compressive loading environment on tendon function, specifically as it relates to age-related rotator cuff degeneration. The central hypothesis of the proposal is that the chronic inflammatory environment and other age-related changes in tenocyte processes, combined with an increase in compressive loading due to poor posture and musculature, may lead to rotator cuff degeneration.
We aim to investigate this hypothesis by creating a powerful in vitro model of compression-induced tendon damage using the murine rotator cuff, and to use this model to decouple the contributions of natural aging and inflammation in the development of tissue damage. The project outlined in this application combines fundamental basic research importance with translation directed toward the future diagnosis and therapeutic treatment of early stage tendon degeneration. In addition, this proposal details a series of career development activities that will aid me along the journey to becoming an independent investigator. The Massachusetts Institute of Technology provides me with an exceptional environment, providing the resources to investigate the proposed scientific studies and develop the skills necessary for successful career development. Furthermore, the assembled career advisory team, along with new mentoring relationships I am developing specifically in the aging biology community, will give me the experience and advising necessary to accelerate my career and begin my own research program as an independent faculty advisor.
Rotator cuff disease and injuries affect over half the population over the age of 60, causing significant pain, disability and decreased independence for the aging population. The overall goal of this proposal is to understand how the biology of natural aging influences the pathogenesis of rotator cuff degeneration in the case of compression-induced injury. Specifically, we will to identify age-related changes in the tenocyte response to compressive and tensile mechanical loading and decouple the roles of aging and inflammation in the progression of degenerative changes in the rotator cuff with the hopes of ultimately assisting clinical research in determining appropriate treatment and rehabilitation protocols for early stage tendon disease.
