Expression and Function of the EAATs in the Heart

描述(由申请人提供)： 这项建议详细说明了一项为期5年的培训计划，该计划旨在发展必要的技能，作为学术医学职业生涯的一部分，在基础科学领域进行独立研究。首席研究员是一名经过委员会认证的儿科医生，接受过儿科心脏病学方面的培训，目前在匹兹堡大学担任终身教职，至少有75%的保护时间用于研究。 该培训计划以心脏细胞生理学的研究为中心，因为它与胎儿和新生儿的心脏谷氨酸代谢有关。伊恩·雷诺兹博士将指导首席调查员的培训。他是线粒体生物学领域的知名研究员。心脏开发领域备受尊敬的研究员布拉德利·凯勒博士将担任共同发起人。这两家公司在培训成功的研究人员方面都有丰富的经验，他们的技能和兴趣的结合将为申请者的研究努力提供全面的支持。 拉尔夫博士的研究将调查心脏兴奋性氨基酸转运体(EAATs)对谷氨酸运输的作用。他的初步数据表明，心肌细胞中存在EAAT1、EAAT2和EAAT3，EAAT1定位于线粒体膜内。了解谷氨酸在心脏中的转运机制，对青紫型先天性心脏病患儿和所有接受体外循环的患者的治疗具有重要意义。本课程将致力于三个具体目标：1)EAAT1、EAAT2、EAAT3和EAAT4在心肌细胞中的定位；2)EAAT1和EAAT4在线粒体中所扮演的功能角色的定义；以及3)提供EAAT2和EAAT3介导谷氨酸进入心肌细胞的直接证据。 匹兹堡大学和匹兹堡儿童医院为实施这项计划提供了理想的环境，因为强大的研究环境和优秀的导师和顾问将在整个计划期限内密切参与。这一组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。

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.