Calcium-mediated modulation of cardiac development

描述（由申请人提供）： 这个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，申请人已经完成了儿科住院医师和儿科心脏病学奖学金。 这个项目将在斯科特·里夫纳博士的指导下进行，他有培养年轻医学博士的经验。和博士他是接受过独立研究训练的科学家，也是受体生物学领域公认的领导者。 申请人打算利用其在肌细胞生物学和先天性心脏病损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集中在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公认的。 初步数据表明，细胞内钙水平的改变和钙下游的信号级联可以显着改变心脏发育。 此外，先前的研究已经证明了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)我将研究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在调节心脏形态发生和心肌细胞分化中的作用。 最后，（3）我将确定钙信号是否调节TAF在发育中的心脏中的表达和功能。 耶鲁大学是生物医学研究的世界领导者，儿科系已经证明自己是培养儿科医生科学家的理想场所。 一个来自耶鲁大学教师的著名咨询委员会将监督申请人在这个项目中的进展。与Rivership指导相结合，这些资源应使申请人能够发展成为一名成功的独立研究者，并为发展心脏病学领域做出巨大贡献。

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.