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骨髓生成分子基础的计划项目。 研究主题集中在基因的鉴定和表征，这些基因在从多能造血干细胞分化的正常途径中至关重要，通过中间祖细胞和前体细胞阶段，成熟分化和功能性中性粒细胞。 这些主题结合在一起，努力提高我们的理解的基因表达在骨髓细胞和特定的途径，调节分化，成熟和功能的髓样细胞的分子解剖。 该计划项目被组织成一个团队的方法，由一个生物信息学核心和一个行政核心支持的五个研究项目的综合追求。 个别项目涉及与同源框基因HoxB 4的功能有关的分子相关性的表征，该基因优先在原始造血干/祖细胞中表达;转录辅因子SHARP及其同种型在造血中的作用的表征;原癌基因Evi 1破坏正常骨髓生成的分子机制的表征;与骨髓特化相关的基因表达的全球基因组分析;以及嗜中性粒细胞特异性基因表达的转录调控研究。 生物信息学核心将提供最先进的数据库管理和分析工具，用于储存和解释这些项目产生的基因组数据。 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，他们具有各种基础研究专业知识，以解决造血中的一些重要问题。

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.