This application seeks support for a specialty board certified (American College of Veterinary Surgeons) equine veterinary surgeon to complete the transition from clinical practice to a career as a translational arthritis researcher. The applican will work at Cornell University under the guidance of Dr. Lisa A. Fortier (PhD advisor, Mentor) and Dr. Larry Bonassar (minor PhD advisor). Dr. Fortier, a clinician-scientist, is an equine orthopedic surgeon and an expert in the fields of osteoarthritis research, cartilage repair, and regenerative medicine. Dr. Larry Bonassar, a biomedical engineer, is an expert in the areas of musculoskeletal tissue engineering and mechanical analysis of cartilage. A well-established collaboration between the Fortier and Bonassar Laboratories is at the core of Cornell's Cartilage Group, an interdisciplinary research, training, and mentoring environment. Both have outstanding records for training graduate students and mentoring postdoctoral associates. This proposal is divided into two phases, a Mentored Phase, and a Transition-to-Independence Phase. During Phase I, the applicant will acquire a deeper understanding of basic cartilage biology, mitochondrial biology, and osteoarthritis, and complete a PhD degree. The applicant and her mentor have assembled an interdisciplinary team of collaborators to advise, mentor, and aid in the research training of the applicant during this phase. They are committed to helping the applicant learn important concepts and research methods needed to complete the proposed studies, and understand the biological significance of their results. They are also dedicated to mentoring the candidate through Phase II, the transition to research independence. In Phase II (Transition to Independence), the applicant will apply the knowledge, skills, and insights gained in Phase I to study impact-induced mitochondrial dysfunction in an vivo model of early ankle post-traumatic osteoarthritis (PTOA) developed in the Fortier laboratory. We expect these studies will further the fundamental understanding of the role of mitochondrial dysfunction in early PTOA, and will provide evidence for the clinical use of mitochondria stabilizing drugs to halt PTOA progression. The applicant will complete a rigorous training program in hypothesis driven research and gain the scientific and beyond-the-bench career skills necessary to establish a career in translational medicine with a niche in the area of cartilage mitochondrial pathobiology.
After joint injury, clinical signs of arthritis (pain and dysfunction) often lag years or decades behind irreversible cartilage destruction, at which time only palliative treatment can be offered. In this proposal, we will study the role of mitochondria n the initiation of injury-induced arthritis and test mitoprotective drugs to restore mitochondrial function and prevent cartilage loss. The goal is to develop new strategies to target and stabilize mitochondria after traumatic joint injury, halt disease progression, and prevent chronic pain and disability.
|Bonnevie, Edward D; Delco, Michelle L; Bartell, Lena R et al. (2018) Microscale frictional strains determine chondrocyte fate in loaded cartilage. J Biomech 74:72-78|
|Delco, Michelle L; Bonnevie, Edward D; Bonassar, Lawrence J et al. (2018) Mitochondrial dysfunction is an acute response of articular chondrocytes to mechanical injury. J Orthop Res 36:739-750|
|Delco, Michelle L; Bonnevie, Edward D; Szeto, Hazel S et al. (2018) Mitoprotective therapy preserves chondrocyte viability and prevents cartilage degeneration in an ex vivo model of posttraumatic osteoarthritis. J Orthop Res :|
|Delco, Michelle L; Kennedy, John G; Bonassar, Lawrence J et al. (2017) Post-traumatic osteoarthritis of the ankle: A distinct clinical entity requiring new research approaches. J Orthop Res 35:440-453|