Regulation Mechanisms of Thyroid Hormone Receptors in the Heart

描述(申请者提供)：Ledee博士是一位经验丰富的研究人员，并发表了大量的论文。她目前是迈克尔·波特曼博士实验室的研究科学家。她参与了许多项目，包括：1)研究甲状腺激素治疗或脱机后体外膜氧合机械循环支持后代谢蛋白的变化。2)研究增龄和甲状腺激素治疗后代谢蛋白的变化。她还与部门内的其他私人助理合作。这种环境有利于这种合作，并提供了扩大研究倡议的机会。利迪博士目前正在完成两篇第一批作者论文。她负责培训所有在实验室轮换的医学研究员和本科生。利迪博士已经在波特曼博士的实验室工作了3年，并被灌输到了一个新的研究领域。她的目的是开始心脏代谢方面的独立研究事业，西雅图儿童研究所的资源非常好。除了博学多才的科学家之外，这个物理场所还配备了很好的设备，可以进行利迪博士设想的那种分子实验。利迪博士提出的研究项目是研究老年心脏中甲状腺受体的功能变化。据观察，老年心脏经历了结构、代谢和分子方面的变化；随着老年人口的不断增加，破坏性心血管事件也将增加。之前在实验室中的实验观察到，甲状腺激素治疗可以逆转老年心脏的代谢转变，而不会改变甲状腺受体的表达。基于这一结果，Ledee博士建议研究潜在的甲状腺受体的表观遗传和翻译后修饰调控。此外，在之前的实验中，她发现了几种与TRB1相互作用的蛋白质，这些蛋白质以前没有报道过。她建议研究这种相互作用的机制和潜在的功能作用。她的第三个目标是识别老年心脏中因甲状腺激素治疗而改变表达的蛋白质，以此作为了解随着年龄增长而发生的分子变化的一种方法。总而言之，我相信我的建议解决了人类健康中一个非常严重的问题--心血管衰老。K01基金提供了追求成为独立原则调查员的目标的手段。(摘要结束)

DESCRIPTION (provided by applicant): Dr. Ledee is an experienced research and well published. She is presently a research scientist in the laboratory of Dr. Michael Portman. She is responsible for many projects including: 1) Investigating changes in metabolic proteins post mechanical circulatory support by extracorporeal membrane oxygenation after thyroid hormone treatment or weaning. 2) Investigate the metabolic protein shifts due to aging and post thyroid hormone treatment. She also collaborates with other PIs in the department. The environment is conducive to such collaborations and offers opportunities to expand on research initiatives. Dr. Ledee is presently working on the completion of 2 first authorship papers. She is responsible for training all of the medical fellows and undergraduates that rotate through the lab. Dr. Ledee has been in Dr. Portman's lab for 3 years and has been indoctrinated into a new field of research. It is her intent to embark upon an independent research career in cardiac metabolism, and Seattle Children's Research Institute resources are excellent. In addition to the incredibly knowledgeable scientist the physical place is well equipped for the type of molecular experiments Dr. Ledee has envisioned. The research project Dr. Ledee has proposed investigates thyroid receptors functional changes in the aged heart. The aged heart is observed to undergo structural, metabolic and molecular changes; and with an ever increasing older population damaging cardiovascular events will also increase. Previous experiments in the lab observed that thyroid hormone treatment could reverse the metabolic shift in the aged heart without a change in thyroid receptor expression. Based on this result Dr. Ledee proposed to examine potential epigenetic and post-translational modification regulation of the thyroid receptors. Additionally, in prior experiments she identified several proteins that interact with TRB1, which have not been previously reported. She proposes to examine the mechanisms of the interaction and potential functional role. Her 3rd aim focuses on identifying proteins that have altered expression in response to thyroid hormone treatment in the aged heart as a method to understand the molecular changes that occur with aging. In conclusion, I believe my proposal addresses a very serious problem in human health, cardiovascular aging. The K01 grant offers the means to pursue the goal of being an independent principle investigator. (End of Abstract)