MOLECULAR MECHANISMS OF CONGENITAL HEART DISEASE

该SCOR项目的目标是进一步了解 先天性心脏病的基本机制与使用 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 心脏病学哈佛儿科心脏病学SCOR将汇集 哈佛医学院最优秀的基础科学研究人员 学校及其附属教学医院。每一个参与者， SCOR有一个强大的记录，使原始和基本的 对心血管科学的贡献，因为它涉及到这一目标， 射频消融本SCOR应用程序中描述的项目旨在采取 研究密切相关的科学主题的最大优势 使用不同的模式生物和系统来剖析 心脏形态发生中的转录因子和分泌因子 以及它们在人类和实验动物中的突变， 儿童先天性心脏病患者人群的关联 疾病因此，这份哈佛SCOR申请的题目是“分子生物学”。 先天性心脏病的发病机制，”并由五个独立的 但高度互动的项目和三个核心， 专业技术支持和行政支持， 推动每个项目的进展。具体项目包括： 项目一：心脏特异性同源异型盒基因的功能分析 Csx/Nkx（P.I.- Seigo，Izumo）.项目二：遗传分析 先天性心脏病（P.I.-克莉丝汀E. Seidman; Co-P.I.-乔恩 Seidman）。项目三.诱导细胞凋亡的信号分子的鉴定 心脏形成（P.I.-安德鲁B。Lasser）。项目四：T-Box基因在 先天性心脏和肢体畸形（P.I.- Clifford J. Tabin）。项目五： 先天性心律失常的遗传因素 心脏畸形（P.I.- Charles I. Berul;共同研究者Mark E. Josephson和Edward沃尔什）。小动物生理学核心（主任-詹姆斯 P.摩根）将提供最先进的生理分析， 小鼠心血管系统使用多学科的方法。的 胚胎生理学和成像实验室将是一个独特的资源， 哈佛社区。将开发形态核心， 每个项目的形态学研究。该计划旨在使 明确关注心脏病的分子基础研究 发展及其遗传改变，特别强调 心脏转录因子和分泌因子的研究， 在早期心脏发生中的重要作用。所有项目都广泛 在科学主题和技术方面都是相互联系的 同时利用实验和临床方法。 该计划联合了基础科学部门和临床心脏病学 哈佛医学院的课程。SCOR主任拥有广泛的 组织互动多学科项目的经验， 包括临床和学术学科。SCOR已满 机构支持，使方案取得成功。我们认为这 SCOR将产生许多新的发现，这些发现对我们理解 先天性心脏病，同时旨在提供丰富的 下一代心血管疾病的培训机会 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.