Molecular Basis of Myelopoiesis

描述(由申请人提供)： 耶鲁大学医学院的合作研究人员共同开发了一个关于骨髓生成分子基础的项目。研究主题集中于鉴定和表征在从多能造血干细胞到成熟、分化和功能性中性粒细胞的正常分化途径中至关重要的基因。这些主题结合在一起，努力提高我们对骨髓生成基因表达的分子解剖学以及调节髓系细胞分化、成熟和功能的特定途径的理解。该计划项目被组织成一个团队方法，由一个生物信息学核心和一个管理核心支持五个研究项目的综合追求。这些单独的项目涉及与同源盒基因HOXB4的功能相关的分子的表征，该基因在原始的造血干/祖细胞中优先表达；转录辅助因子Sharp及其异构体在造血中的作用的表征；原癌基因Evi1破坏正常骨髓生成的分子机制的表征；与髓系规范相关的基因表达的全球基因组分析；以及中性粒细胞特异性基因表达的转录调控研究。生物信息学核心将为存储和解释这些项目产生的基因组数据提供最先进的数据库管理和分析工具。该计划项目申请汇集了来自该机构四个不同部门的研究人员，他们拥有广泛的基础研究专业知识，以解决一些重要的造血问题。

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.