Expression and Function of the EAATs in the Heart

EAAT 在心脏中的表达和功能

• 批准号: 6899015
• 负责人: John Carter Ralphe
• 金额: $ 12.66万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6899015
• 关键词: cardiac myocytes; cardiovascular function; excitatory aminoacid; gene expression; glutamate transporter; glutamates; laboratory rat; mitochondrial membrane; neurotransmitter metabolism; neurotransmitter transport; pediatrics; protein localization; training

DESCRIPTION (provided by applicant): This proposal details a 5-year training program to develop the skills necessary to pursue independent research in basic science as part of a career in academic medicine. The principal investigator is a board-certified pediatrician, trained in pediatric cardiology, currently holding a tenure-track faculty appointment at the University of Pittsburgh with a minimum of 75% protected time for research. This training program centers upon studies of cardiac cellular physiology as it relates to fetal and neonatal cardiac glutamate metabolism. Dr. Ian Reynolds will mentor the principal investigator's training. He is a well-established investigator in the field of mitochondrial biology. Dr. Bradley Keller, a highly regarded researcher in cardiac development, will act as co-sponsor. Both have extensive experience in training individuals who have gone on to successful research careers and the combination of their skills and interests will provide comprehensive support of the applicant's research efforts. Dr. Ralphe's research will investigate the role of glutamate transport by the excitatory amino acid transporters (EAATs) in the heart. His preliminary data has demonstrated the presence of EAAT1, EAAT2, and EAAT3 in cardiomyocytes, with EAAT1 localizing to the inner mitochondrial membrane. Understanding the mechanisms of glutamate transport in the heart has important implications in the management of children with cyanotic congenital heart defects and all patients undergoing cardiopulmonary bypass. Three specific aims will be addressed: 1) the demonstration of localization of EAAT1, EAAT2, EAAT3 and EAAT4 in the cardiomyocyte; 2) the definition of the functional roles played by EAAT1 and EAAT4 within the mitochondria; and 3) the provision of direct evidence that EAAT2 and EAAT3 mediate glutamate uptake into the cardiomyocyte. The University of Pittsburgh and the Children's Hospital of Pittsburgh provide an ideal setting in which to undertake this proposal due to the strong research environment and the availability of outstanding mentors and advisors who will remain closely involved throughout the tenure of this program. This combination will maximize the potential for the principal investigator to develop into a successful independent research scientist.

描述（由申请人提供）： 该提案详细介绍了一项为期 5 年的培训计划，旨在培养在基础科学领域进行独立研究所需的技能，作为学术医学职业的一部分。 主要研究者是一位经过委员会认证的儿科医生，接受过儿科心脏病学培训，目前在匹兹堡大学担任终身教授，至少有 75% 的受保护时间用于研究。 该培训计划以心脏细胞生理学研究为中心，因为它与胎儿和新生儿心脏谷氨酸代谢有关。 伊恩·雷诺兹博士将指导首席研究员的培训。 他是线粒体生物学领域的知名研究者。 Bradley Keller 博士是一位备受尊敬的心脏发育研究专家，他将担任联合发起人。 两人在培养成功研究生涯的个人方面都拥有丰富的经验，他们的技能和兴趣的结合将为申请人的研究工作提供全面的支持。 Ralphe 博士的研究将调查心脏中兴奋性氨基酸转运蛋白 (EAAT) 转运谷氨酸的作用。 他的初步数据表明心肌细胞中存在 EAAT1、EAAT2 和 EAAT3，其中 EAAT1 定位于线粒体内膜。 了解心脏中谷氨酸转运的机制对于治疗患有紫绀型先天性心脏缺陷的儿童和所有接受体外循环的患者具有重要意义。 将解决三个具体目标：1）演示 EAAT1、EAAT2、EAAT3 和 EAAT4 在心肌细胞中的定位； 2) EAAT1和EAAT4在线粒体内发挥的功能作用的定义； 3)提供EAAT2和EAAT3介导心肌细胞摄取谷氨酸的直接证据。 匹兹堡大学和匹兹堡儿童医院提供了一个理想的环境来开展这项提案，因为它们拥有强大的研究环境以及优秀的导师和顾问，他们将在整个项目的整个任期内密切参与。 这种结合将最大限度地发挥首席研究员发展成为一名成功的独立研究科学家的潜力。