Calcium-mediated modulation of cardiac development

钙介导的心脏发育调节

• 批准号: 6609725
• 负责人: George A Porter
• 金额: $ 13.15万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-08 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6609725
• 关键词: calcium flux; calmodulin dependent protein kinase; cardiac myocytes; cell differentiation; congenital heart disorder; developmental genetics; heart; histogenesis; laboratory mouse; mammalian embryology; transcription factor

DESCRIPTION (provided by applicant): This Mentored Clinical Scientist Developmental Award application describes a program of career development and training for the applicant, who has completed a residency in pediatrics and a fellowship in pediatric cardiology. This program will be under the mentorship of Dr. Scott Rivkees, who has experience grooming young M.D. and Ph.D. trained scientists for independent research and who is a recognized leader in the field of receptor biology. The applicant intends to study the origins of abnormal heart development by using his expertise in muscle cell biology and in the physiology of congenital heart lesions and by continuing his training in developmental molecular biology. The research plan presented herein will focus on the role of intracellular calcium signals in controlling cardiac development. Calcium's role as an intracellular messenger is well-recognized. Preliminary data demonstrate that alterations in intracellular calcium levels and the signal cascades that lie downstream of calcium can dramatically alter cardiac development. In addition, previous studies have demonstrated the presence of calcium regulatory mechanisms in the early mammalian heart. To further understand these phenomena, following Specific Aims are proposed. (1) I will examine whether a reduction of intracellular calcium levels affect cardiac myocyte differentiation and cardiac morphogenesis. (2) I will examine the role of CaMK II in the regulation of cardiac morphogenesis and myocyte differentiation. Finally, (3) I will determine whether calcium signals modulate TAF expression and function in the developing heart. Yale University is a world leader in biomedical research, and the Department of Pediatrics has proven itself to be an ideal setting to train pediatric physician-scientists. A prestigious advisory committee drawn from the faculty at Yale will monitor the applicant's progress during this project. Combined with Dr. Rivkees mentorship, these resources should allow the applicant to develop into a successful independent investigator and make great contributions to the field of developmental cardiology.

描述（由申请人提供）： 该指导临床科学家发展奖申请描述了申请人的职业发展和培训计划，申请人已完成儿科住院医师培训和儿科心脏病学研究金。 该项目将由 Scott Rivkees 博士指导，他拥有培养年轻医学博士和博士的经验。训练有素的独立研究科学家，是受体生物学领域公认的领导者。 申请人打算利用他在肌肉细胞生物学和先天性心脏病变生理学方面的专业知识，并继续接受发育分子生物学方面的培训，研究异常心脏发育的起源。 本文提出的研究计划将重点关注细胞内钙信号在控制心脏发育中的作用。 钙作为细胞内信使的作用是众所周知的。 初步数据表明，细胞内钙水平和钙下游信号级联的改变可以显着改变心脏发育。 此外，先前的研究已经证明早期哺乳动物心脏中存在钙调节机制。 为了进一步了解这些现象，提出了以下具体目标。 (1)我将检查细胞内钙水平的降低是否影响心肌细胞分化和心脏形态发生。 (2)我将研究CaMK II在心脏形态发生和肌细胞分化调节中的作用。 最后，(3) 我将确定钙信号是否调节发育中心脏中的 TAF 表达和功能。 耶鲁大学在生物医学研究方面处于世界领先地位，儿科系已证明自己是培养儿科医师科学家的理想场所。 由耶鲁大学教师组成的著名咨询委员会将监督申请人在该项目期间的进展。结合 Rivkees 博士的指导，这些资源应该使申请人能够发展成为一名成功的独立研究者，并为发育心脏病学领域做出巨大贡献。