Calcium-mediated modulation of cardiac development

钙介导的心脏发育调节

• 批准号: 6898270
• 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/6898270
• 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）： 这项受过指导的临床科学家发展奖申请介绍了申请人的职业发展和培训计划，后者已经完成了儿科居民和儿科心脏病学研究金的居民。 该计划将在Scott Rivkees博士的指导下，他在Young M.D.和Ph.D.上的经验经验。受过独立研究的训练有素的科学家，并且是受体生物学领域的公认领导者。 申请人打算通过利用其在肌肉细胞生物学和先天性心脏病变的生理学方面的专业知识来研究异常心脏发育的起源，并继续他在发育分子生物学方面的培训。 本文介绍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已得到充分认可。 初步数据表明，细胞内钙水平和位于钙下游的信号级联反应可以极大地改变心脏发育。 此外，先前的研究表明，早期哺乳动物心脏中存在钙调节机制。 为了进一步理解这些现象，提出了以下特定目标。 （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在心脏形态发生和心肌分化的调节中的作用。 最后，（3）我将确定钙信号是否调节发育中心的TAF表达和功能。 耶鲁大学是生物医学研究的世界领导者，儿科系证明自己是培训小儿医师科学家的理想场所。 一个享有声望的咨询委员会从耶鲁大学的教职员工中提取的委员会将在此项目期间监视申请人的进度。结合Rivkees博士的指导，这些资源应使申请人能够发展成为成功的独立研究者，并为发展心脏病学领域做出巨大贡献。