Molecular Basis of Myelopoiesis

骨髓生成的分子基础

• 批准号: 6809333
• 负责人: BERNARD G FORGET
• 金额: $ 189.06万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6809333
• 关键词: clinical research; hematopoiesis; human tissue; myeloid stem cell

DESCRIPTION (provided by applicant): Collaborating Investigators at Yale University School of Medicine have jointly developed a Program Project on the molecular basis of myelopoiesis. The research themes focus on the identification and characterization of genes that are critical in the normal pathway of differentiation from the pluripotent hematopoietic stem cell, through intermediate progenitor and precursor cell stages, to mature differentiated and functional neutrophils. These themes coalesce in efforts to improve our understanding of the molecular anatomy of gene expression in myelopoiesis and the specific pathways that regulate the differentiation, maturation and function of myeloid cells. This Program Project is organized into a team approach for the integrated pursuit of five research projects supported by one bioinformatics core and one administrative core. The individual projects address the characterization of the molecular correlates associated with the function of the homeobox gene HoxB4 that is preferentially expressed in primitive hematopoietic stem/progenitor cells; characterization of the role in hematopoiesis of the transcriptional co-factor SHARP and its isoforms; characterization of the molecular mechanisms by which the proto-oncogene Evi1 disrupts normal myelopoiesis; global genomic analysis of gene expression associated with myeloid specification; and study of the transcriptional regulation of neutrophil-specific gene expression. The bioinformatics core will provide state-of-the-art database management and analytical tools for the storing and interpretation of the genomic data generated by these projects. This Program Project application brings together investigators from four different departments of the institution, with a wide variety of basic research expertise to address a number of important questions in hematopoiesis.

描述（由申请人提供）： 耶鲁大学医学学院的调查人员合作，在骨髓卵子的分子基础上共同开发了一个计划项目。 研究主题着重于从多能造血干细胞（通过中间祖细胞和前体细胞阶段）到成熟分化和功能性嗜中性粒细胞的正常造血干细胞的鉴定和表征。 这些主题合并为了提高我们对脊髓脉中基因表达的分子解剖结构以及调节髓样细胞分化，成熟和功能的特定途径。 该计划项目被组织成一个团队方法，以综合追求五个由一个生物信息学核心和一个行政核心支持的研究项目。 单个项目解决了分子的表征与同源造血茎/祖细胞中优先表达的同型基因HOXB4的功能相关。转录共同因素尖锐及其同工型在造血中的作用的表征；原始癌基因EVI1破坏正常髓鞘的分子机制的表征；与髓样规范相关的基因表达的全球基因组分析；并研究中性粒细胞特异性基因表达的转录调节。 生物信息学核心将为这些项目生成的基因组数据的存储和解释提供最新的数据库管理和分析工具。 该计划项目的应用程序汇集了来自该机构四个不同部门的调查人员，并具有各种基础研究专业知识，以解决造血中的许多重要问题。