Regulation Mechanisms of Thyroid Hormone Receptors in the Heart

心脏甲状腺激素受体的调节机制

• 批准号: 9287926
• 负责人: Dolena Roselle Ledee
• 金额: $ 15.87万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-25 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9287926
• 关键词: Address; Age; Aging; Aging-Related Process; Atherosclerosis; Authorship; Ca(2+)-Transporting ATPase; Cardiac; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Cessation of life; Child; Collaborations; Data; Disease; Elderly; Elements; Environment; Epigenetic Process; Event; Exhibits; Extracorporeal Membrane Oxygenation; Functional disorder; Gene Expression; Gene Targeting; Genes; Goals; Grant; Growth; Health; Heart; Heart failure; Human; Hypertension; Individual; Laboratories; Malignant Neoplasms; Mechanics; Mediating; Medical; Metabolic; Methods; Modification; Molecular; Mus; Myosin Heavy Chains; Older Population; Organ; Paper; Population; Post-Translational Protein Processing; Protein Isoforms; Proteins; Publishing; Regulation; Reporting; Research; Research Institute; Research Personnel; Research Project Grants; Resources; Response Elements; Role; Sarcoplasmic Reticulum; Scientist; Testing; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroid Hormone Receptor; Thyroid Hormones; Tissues; Training; Weaning; age group; age related; aged; base; career; chronotropic; experience; experimental study; heart function; heart metabolism; hormone deficiency; hormone regulation; hormone response element; insight; promoter; protein complex; receptor; receptor expression; response; undergraduate student

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)

描述（由申请人提供）：Ledee博士是一位经验丰富的研究人员，并发表过许多文章。她目前是迈克尔·波特曼博士实验室的研究科学家。她负责的项目包括：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)研究衰老和甲状腺激素治疗后代谢蛋白的变化。她还与部门的其他pi合作。环境有利于这种合作，并为扩大研究计划提供了机会。Ledee博士目前正在完成两篇第一作者论文。她负责培训所有在实验室轮转的医学研究员和本科生。Ledee博士已经在波特曼博士的实验室工作了3年，并被灌输到一个新的研究领域。她打算在心脏代谢方面开始独立的研究生涯，而西雅图儿童研究所的资源非常好。除了知识渊博的科学家外，这个物理场所还为Ledee博士所设想的分子实验提供了良好的设备。Ledee博士提出的研究项目是研究老年人心脏中甲状腺受体的功能变化。观察到老年心脏发生结构、代谢和分子变化；随着老年人口的不断增加，破坏性心血管事件也会增加。先前在实验室的实验观察到，甲状腺激素治疗可以逆转衰老心脏的代谢变化，而不会改变甲状腺受体的表达。基于这一结果，Ledee博士建议研究甲状腺受体潜在的表观遗传和翻译后修饰调节。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衰老心脏中甲状腺激素治疗后表达改变的蛋白质，以此作为了解衰老过程中发生的分子变化的一种方法。总之，我相信我的提议解决了人类健康中一个非常严重的问题——心血管老化。K01资助为追求成为独立的主要研究者的目标提供了手段。（摘要结束）