Mitochondrial dysfunction as a link between cartilage injury and osteoarthritis

项目总结/摘要 该申请寻求专业委员会认证（美国兽医学院）的支持 马兽医完成从临床实践过渡到职业生涯作为一个翻译关节炎 研究员申请人将在康奈尔大学工作，由丽莎A博士指导。Fortier（博士生导师， 导师）和拉里·博纳萨博士（未成年博士生导师）。Fortier博士是一名临床科学家， 他是一位外科医生，也是骨关节炎研究、软骨修复和再生医学领域的专家。博士 生物医学工程师Larry Bonassar是肌肉骨骼组织工程领域的专家， 软骨的力学分析。福蒂埃和博纳萨之间的良好合作 实验室是康奈尔大学Carnell Group的核心，Carnell Group是一个跨学科的研究，培训和指导组织。 环境两人在培养研究生和指导博士后方面都有出色的记录 合伙人 该建议分为两个阶段，指导阶段和过渡到独立阶段。期间 第一阶段，申请人将获得基础软骨生物学，线粒体生物学， 骨关节炎，并完成博士学位。申请人和她的导师已经组建了一个跨学科的 合作者团队在此阶段为申请人的研究培训提供建议，指导和帮助。 他们致力于帮助申请人学习重要的概念和研究方法， 完成拟议的研究，并了解其结果的生物学意义。他们也是 致力于指导候选人通过第二阶段，过渡到研究独立。 在第二阶段（向独立过渡），申请人将应用在 I期研究踝关节创伤后早期体内模型中撞击诱导的线粒体功能障碍 骨关节炎（PTOA）在福捷实验室开发。我们希望这些研究将进一步促进基本的 了解线粒体功能障碍在PTOA早期的作用，并将为临床提供证据。 使用线粒体稳定药物来阻止PTOA进展。申请人将完成严格的培训 在假设驱动的研究计划，并获得必要的科学和超越板凳的职业技能， 在软骨线粒体病理生物学领域建立转化医学的职业生涯。

Project Summary/Abstract 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 applicant 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.