Expression and Function of the EAATs in the Heart

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，以培养在基础科学领域进行独立研究所需的技能，作为学术医学职业生涯的一部分。 主要研究者是一名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职，至少有75%的研究时间受到保护。 这个培训计划的中心是心脏细胞生理学的研究，因为它涉及到胎儿和新生儿心脏谷氨酸代谢。 伊恩·雷诺兹博士将指导主要研究者的培训。 他是线粒体生物学领域的知名研究者。 布拉德利凯勒博士，一位在心脏发育方面备受推崇的研究人员，将担任共同赞助人。 两者都有丰富的经验，在培训个人谁已经去了成功的研究事业和他们的技能和兴趣的结合将提供申请人的研究工作的全面支持。 博士Ralphe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EAAT 1、EAAT 2和EAAT 3，EAAT 1定位于线粒体内膜。 了解心脏中谷氨酸转运的机制对紫绀型先天性心脏病患儿和所有接受体外循环的患者的管理具有重要意义。 将解决三个具体目标：1）EAAT 1，EAAT 2，EAAT 3和EAAT 4在心肌细胞中的定位的证明; 2）EAAT 1和EAAT 4在线粒体中发挥的功能作用的定义;和3）提供直接证据，EAAT 2和EAAT 3介导谷氨酸摄取到心肌细胞。 匹兹堡大学和匹兹堡儿童医院提供了一个理想的环境，由于强大的研究环境和优秀的导师和顾问的可用性，他们将在整个项目的任期内密切参与。 这种结合将最大限度地发挥主要研究者发展成为一名成功的独立研究科学家的潜力。

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.