Metabolism, Skeletal Muscle, Cardiac Disease, Exercise

候选人：候选人约翰·P·孔希拉斯博士，是一名研究助理， 心血管生理学的广泛培训，包括其他生物系统和及时 分子技术Konhilas 1博士的直接职业目标是获得研究和专业技能 这是实现他的长期目标所必需的，即建立一个独立的、由外部资助的翻译机构。 一项研究计划，重点是在心脏疾病状态下调节骨骼肌特性 以及动物的运动与人类疾病的关系。建议的K 01开发计划将提供博士。 Konhilas拥有额外的经验和培训来实现这一目标。 职业发展计划：奖励期间的培训活动包括：（1）获取新的和完善的 目前的研究技能，（2）结构化的活动，包括科学完整性，生物统计学课程，以及 参加/发表期刊俱乐部、科学会议和指导互动。环境：博士 Konhilas组建了一个导师团队，为提案的各个方面提供指导。赞助商， 博士Leslie Leinwand，是一位知名的校外资助科学家，也是一位久经考验的导师。她有 provided提供了a productive生产and nursing培育research研究environment环境necessary必要for career职业development发展. 研究：有待检验的假设指出，骨骼肌的氧化能力在运动期间降低。 心脏病状态，可以通过运动训练恢复。为了研究关键代谢的作用， 在这一过程中，脂蛋白脂肪酶或过氧化物酶体增殖物激活受体α将介导 通过全身施用腺相关病毒（AAV）载体在骨骼肌中被遗传破坏 在心脏病进展和运动期间的特定时间。所有动物的骨骼肌 分析了肌肉组织中的肌球蛋白含量、肌纤维大小和氧化能力。 相关性：严重的骨骼肌无力和劳累时的疲劳是主要的临床特征， 发生在充血性心力衰竭（CHF）患者中。运动不耐症在CHF中可以逆转 有氧运动不依赖于中枢心脏效应。因此，它具有重要的临床意义。 重要的是，确定心脏疾病、相关异常 骨骼肌和运动。该提案将研究这种疾病过程的特定调节剂， 评估它们在疾病和运动恢复过程中的作用。

Candidate: The candidate, John P. Konhilas, Ph.D., is a research associate endeavoring to broaden his extensive training in cardiovascular physiology to encompass additional biological systems and timely molecular techniques. Dr. Konhilas1 immediate career goal is to acquire the research and professional skills necessary for achieving his long-term goal of developing an independent, extramurally-funded translational research program focusing on the regulation of skeletal muscle characteristics during cardiac disease states and exercise in animals as it relates to human disease. The proposed K01 development plan will provide Dr. Konhilas with the additional experience and training to achieve this goal. Career Development Plan: Training activities during the award period include, (1) acquiring new and refining present research skills, (2) structured activities including coursework in scientific integrity, biostatistics, and attendance/presentation at journal clubs, scientific meetings, and mentoring interactions. Environment: Dr. Konhilas has assembled a team of mentors to provide guidance in every facet of the proposal. The sponsor, Dr. Leslie Leinwand, is a well-established extramurallyfunded scientist and a proven mentor. She has provided a productive and nurturing research environment necessaryfor career development. Research: The hypothesis to be tested states that the oxidative capacity of skeletal muscle is reduced during cardiac disease states and can be recovered by exercise training. To examine the role of critical metabolic mediators in this process, lipoprotein lipase or peroxisome proliferator-activated receptor alpha will be genetically disrupted in skeletal muscle by systemic administration of adeno-associated viral (AAV) vectors at specific times during cardiac disease progression and exercise. In all animals, the skeletal muscles will be analyzed for MyHC content, muscle fiber size, and oxidative capacity. Relevance: Severe skeletal muscle weaknessand fatigue upon exertion are major clinical features that occur in patients with congestive heart failure (CHF). The exercise intolerance can be reversed in CHF patients with aerobic exercise independent of central cardiac effects. Therefore, it is of major clinical significance that the mechanistic link be determined between cardiac disease, the associated abnormalities in skeletal muscle, and exercise. This proposal will examine specific regulators of this disease process and evaluate their role during disease and exercise recovery.