MOLECULAR MECHANISMS OF CONGENITAL HEART DISEASE

这个SCOR项目的目标是加深对 先天性心脏病的基本机制与应用 最新的分子生物学、发育生物学、 人类遗传学、小动物心脏生理学和临床儿科 心脏科。哈佛儿科心脏病学SCOR将汇集 哈佛医学院一些最优秀的基础科学研究人员 学校及其附属教学医院。本次活动的每一位参与者 SCOR在制作原创和基础产品方面有着很好的记录 对心血管科学的贡献，因为它与这一目标有关 RFA。此SCOR应用程序中描述的项目旨在 研究密切相关的科学主题的最大优势 用不同的模式生物和系统来剖析 转录因子和分泌因子在心脏形态发生中的作用 以及它们在人类和实验动物中的突变，以及它们的 与儿童先天性心脏病患者群体的关联 疾病。因此，这份哈佛大学SCOR申请的标题是 先天性心脏病的机制》，由五个独立的 但高度互动的项目和三个核心提供了高度 专门的技术支持以及行政支持 促进每个项目的进度。具体项目包括： 项目I：心脏特异同源框基因的功能分析 CSX/NKX(P.I.-Seigo，Izumo)项目二：遗传遗传分析 先天性心脏病(P.I.-Christine E.Seidman；Co-P.I.-Jon 塞德曼)。项目III.识别诱导信号的分子 心脏形成(P.I.-安德鲁·B·拉塞尔)。项目IV：T-Box基因在 先天性心脏和肢体畸形(P.I.-Clifford J.Tabin)。项目V： 先天性心律失常发生的遗传决定因素 心脏畸形(P.I.-Charles I.Berul；共同调查者Mark E. 约瑟夫森和爱德华·沃尔什)。小动物生理学核心(导演-詹姆斯 P·摩根)将提供最先进的生理分析 使用多学科方法研究小鼠心血管系统。这个 胚胎生理学和影像实验室将是 哈佛社区。将开发形态核心以促进 每个项目的形态研究。该计划被设计为具有 明确重点研究心脏疾病的分子基础 发育及其基因改变，特别强调 心脏转录因子和分泌因子的研究进展 在早期心脏发生中的关键作用。所有项目都是广泛的 科学主题和技术方面的相互联系 同时利用实验和临床方法。 该计划将基础科学系和临床心脏病学联合起来 哈佛大学医学院的课程。SCOR主任拥有广泛的 组织互动式多学科项目的经验 涵盖临床和学术两个学科。SCOR已经满了 机构支持，以使该计划取得成功。我们相信这一点 SCOR将产生许多新的发现，这对我们理解 同时也为先天性心脏病提供了丰富的 为下一代心血管疾病提供培训机会 科学家和临床医生。

The goal of this SCOR project is to further the understanding of the fundamental mechanism of congenital heart disease with the use of the state-of-the-art technology of molecular biology, developmental biology, human genetics, small animal cardiac physiology, and clinical pediatric cardiology. The Harvard SCOR in Pediatric Cardiology would bring together some of the finest basic science research faculty of the Harvard Medical School and its affiliated teaching hospitals. Each participant of this SCOR has a strong track record of making original and fundamental contributions to cardiovascular sciences as it relates to the aim of this RFA. The projects described in this SCOR application are designed to take the maximum advantage of studying the closely related scientific theme using the different model organisms and system to dissect the role of transcription factors and secreted factors in the cardiac morphogenesis and their mutations in human and in experimental animals, as well as their linkage into the population of pediatric patients with congenital heart disease. Accordingly, this Harvard SCOR application is entitled "Molecular Mechanisms of Congenital Heart Disease," and consists of five independent but highly interactive projects and three cores that provide highly specialized technological support as well as administrative support to facilitate the progress of each project. Specific projects include: Project I: Functional Analysis of the Cardiac Specific Homeobox Gene Csx/Nkx (P.I.-Seigo, Izumo). Project II: Genetic Analytic of Inherited Congenital Heart Diseases (P.I.-Christine E. Seidman; Co-P.I.-Jon Seidman). Project III. Identification of Signaling Molecules that Induce Heart Formation (P.I.-Andrew B. Lasser). Project IV: T-Box Gene in Congenital Heart and Limb Deformities (P.I.-Clifford J. Tabin). Project V: Genetic Determinants of Arrythmia Development Associated with Congenital Heart Malformation (P.I.-Charles I. Berul; Co-Investigators Mark E. Josephson and Edward Walsh). Small Animal Physiology Core (Director- James P. Morgan) will provide the state-of-the-art physiological analysis of the murine cardiovascular system using a multi-disciplinary approach. The Embryo Physiology and Imaging Laboratory will be a unique resource to the Harvard community. Morphology Core will be developed to facilitate morphological studies by each Project. The program is designed to have clear focus on the investigations of the molecular basis for cardiac development and their genetic alterations with particular emphasis on the studies of cardiac transcription factors and secreted factors that play critical roles in early cardiogenesis. All projects are extensively interconnected both in scientific theme and the technological aspects while taking advantage of both experimental and clinical methodologies. The program unites both basic science departments and clinical cardiology programs of Harvard Medical Campus. The SCOR Director has extensive experiences in organizing interactive multi-disciplinary programs that encompasses both clinical and academic disciplines. The SCOR has full institutional support to make the program successful. We believe that this SCOR will generate many new findings fundamental to our understanding of congenital heart disease and at the same time is designed to provide rich training opportunities for the next generation of cardiovascular scientists and clinicians.