Mitochondrial dysfunction as a link between cartilage injury and osteoarthritis

项目摘要/摘要 此应用程序寻求对专业委员会认证(美国兽医学院)的支持 马兽医完成从临床执业到转化性关节炎职业的过渡 研究员。申请者将在康奈尔大学工作，由Lisa A.Fortier博士(博士导师， 导师)和拉里·博纳萨尔博士(博士生辅导员)。福蒂埃医生是一名临床科学家，也是一名马匹整形外科医生。 他是一名外科医生，也是骨关节炎研究、软骨修复和再生医学领域的专家。Dr。 生物医学工程师拉里·博纳萨尔是肌肉骨骼组织工程领域的专家， 软骨的力学分析。Fortier和Bonassar之间久负盛名的合作 实验室是康奈尔大学软骨小组的核心，是一个跨学科的研究、培训和指导机构 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。 该提案分为两个阶段，即指导阶段和向独立过渡阶段。在.期间 第一阶段，申请者将对基本软骨生物学、线粒体生物学和 骨关节炎，并完成博士学位。申请者和她的导师已经组建了一个跨学科的 在此阶段为申请者的研究培训提供建议、指导和帮助的合作者团队。 他们致力于帮助申请人学习所需的重要概念和研究方法 完成拟议的研究，并了解其结果的生物学意义。他们也是 致力于指导候选人完成第二阶段，即向研究独立的过渡。 在第二阶段(向独立的过渡)中，申请者将应用在 在创伤后早期踝关节活体模型中研究撞击诱导的线粒体功能障碍的第一阶段 骨性关节炎(PTOA)是在Fortier实验室开发的。我们预计这些研究将进一步推动 了解线粒体功能障碍在早期PTOA中的作用，将为临床治疗提供依据 使用线粒体稳定剂来阻止PTOA的进展。申请者将完成严格的培训 计划假说驱动的研究，并获得必要的科学和超越板凳的职业技能 在转化医学领域建立自己的事业，在软骨线粒体病理生物学领域占有一席之地。

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.