Project 3: Role of Glycosaminoglycans in Hematopoiesis

项目 3 – 项目摘要/摘要 糖胺聚糖 (GAG) 有助于多种且常常相反的功能，例如细胞功能 增殖和凋亡、自我更新和分化。然而，人们对此知之甚少 诱导这些功能的确切 GAG 序列。尽管对本计划项目特别重要 GAG 是骨髓 (BM) 微环境的重要组成部分，是骨髓 (BM) 微环境的具体细节 GAG 调节造血细胞命运；这些相互作用是否具有选择性/特异性；以及是否是 GAG 或 GAG 样分子可用于治疗目的仍知之甚少。该项目重点 阐明对造血和血小板生成重要的 GAG 结构-功能关系。三 提出的目标包括 1) 开发生物样本 GAGactome 阐明技术， 特别是骨髓的细胞和微环境； 2) 使用合成 GAG 模拟物库 用于调节造血结果； 3) 阐明 GAG 识别的特异性和功能 唾液酸转移酶 ST6Gal-1。这些目标的结果将是精确的结构-功能关系 诱导造血功能的 GAG。特别是在造血作用方面，该项目旨在回答 GAG 是否调节造血细胞命运的问题。如果是这样，GAG 相互作用是否具有选择性？如果 选择性的，GAG 序列或 GAG 模拟物能否用于治疗造血系统疾病？ 总体而言，该项目贡献了该领域的知识、工具/技术和有治疗前景的药物 造血和血小板生成。

Project 3 – Project Summary/Abstract Glycosaminoglycans (GAGs) contribute to myriad, and very often opposing, functions such as cellular proliferation as well as apoptosis, self-renewal as well as differentiation. Yet, precious little is understood about the exact GAG sequences that induce these functions. Of particular importance to this program project, although GAGs are significant components of the bone marrow (BM) microenvironment, the nuts and bolts of whether GAGs modulate hematopoietic cell fate; whether these interactions are selective/specific; and whether GAG or GAG-like molecules can be harnessed for therapeutic purposes remain poorly understood. This project focuses on elucidating the GAG structure–function relationships of importance to hematopoiesis & thrombopoiesis. Three aims are proposed including 1) Develop Technology for Elucidation of GAGactomes of Biological Samples, especially Cells and Microenvironment of the Bone Marrow; 2) Employ the Library of Synthetic GAG Mimetics for Modulation of Hematopoietic Outcomes; and 3) Elucidate Specificity and Function of GAG Recognition of Sialyl Transferase ST6Gal-1. The outcomes of these aims will be the precise structure–function relationships in GAGs that induce hematopoietic functions. Specifically with respect to hematopoiesis, the project aims to answer the question of whether GAGs modulate hematopoietic cell fate. If so, are GAG interactions are selective? If selective, can GAG sequences or mimetics of GAGs be harnessed as therapeutics for hematopoietic disorders? Overall, this project contributes knowledge, tools/technology, and therapeutically promising agents in the area of hematopoiesis and thrombopoeisis.