Expression and Function of the EAATs in the Heart

EAAT 在心脏中的表达和功能

• 批准号: 7069039
• 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/7069039
• 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）： 该建议详细介绍了一项为期5年的培训计划，以开发作为学术医学职业的一部分，从事基础科学独立研究所需的技能。 首席研究人员是一名经过董事会认证的儿科医生，接受了儿科心脏病学培训，目前在匹兹堡大学任职期间任命终身教师任命，最少有75％的研究时间进行研究。 该训练计划以与胎儿和新生儿心脏谷氨酸代谢有关的心脏细胞生理学的研究为中心。 伊恩·雷诺兹（Ian Reynolds）博士将指导首席调查员的培训。 他是线粒体生物学领域的成熟研究者。 心脏发展方面备受推崇的研究人员Bradley Keller博士将担任共同提案国。 两者在培训成功研究职业的个人方面都有丰富的经验，并且他们的技能和兴趣相结合将为申请人的研究工作提供全面的支持。 Ralphe博士的研究将研究心脏中兴奋性氨基酸转运蛋白（EAATS）谷氨酸转运的作用。 他的初步数据证明了心肌细胞中EAAT1，EAAT2和EAAT3的存在，EAAT1位于线粒体内部膜。 了解心脏中谷氨酸的机制对患有氰基先天性心脏缺陷的儿童和所有经历心肺旁路的患者的治疗具有重要意义。 将解决三个具体目标：1）eaat1，eaat2，eaat3和eaat4在心肌细胞中的定位； 2）eaat1和eaat4在线粒体中扮演的功能角色的定义； 3）提供直接证据表明EAAT2和EAAT3介导谷氨酸摄取到心肌细胞中。 匹兹堡大学和匹兹堡儿童医院提供了一个理想的环境，可以在此提案中进行该提案，这是由于强大的研究环境以及在该计划任期期间将密切参与的杰出导师和顾问的可用性。 这种组合将使主要研究者发展成为成功的独立研究科学家的潜力。