Project 3: Role of Glycosaminoglycans in Hematopoiesis

项目3：糖胺聚糖在造血中的作用

• 批准号: 10321582
• 负责人: Umesh Ramanlal Desai
• 金额: $ 53.07万
• 依托单位: VERSITI WISCONSIN, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10321582
• 关键词: Affinity; Affinity Chromatography; Algorithms; Apoptosis; Area; B-Lymphocytes; Binding; Binding Proteins; Biochemical; Biological; Bone Marrow; Cell Proliferation; Cell Survival; Cell surface; Cells; Cellular Structures; Clinical; Collaborations; Disease; Environment; Extracellular Matrix; Foundations; GAG Gene; Glycobiology; Glycosaminoglycans; Goals; Granulopoiesis; Growth Factor; Hematopoiesis; Hematopoietic; HepG2; In Vitro; Knowledge; Leg; Length; Leukocyte Elastase; Libraries; Maintenance; Mediating; Megakaryocytes; Molecular; Nature; Outcome; Pathway interactions; Peptide Hydrolases; Physiological; Polymers; Polysaccharides; Proteins; Proteoglycan; Research Personnel; Resort; Role; Sampling; Screening procedure; Specificity; Structure; Structure-Activity Relationship; Sulfate; Technology; Therapeutic; Thrombopoiesis; Time; Transferase; Work; base; design; extracellular; in vivo; macrophage; mimetics; novel; programs; receptor; response; self-renewal; sialylation; tool

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.

项目3 -项目概要/摘要 糖胺聚糖（GAG）有助于无数的，而且往往是相反的，功能，如细胞 增殖以及凋亡、自我更新以及分化。然而，人们对 诱导这些功能的确切GAG序列。对于这个项目来说，虽然 GAG是骨髓（BM）微环境的重要组成部分，无论是骨髓微环境还是骨髓微环境， GAG调节造血细胞的命运;这些相互作用是否是选择性/特异性的;以及GAG或 GAG样分子可用于治疗目的仍然知之甚少。该项目重点 阐明GAG结构-功能关系对造血和血小板生成的重要性。三 提出的目标包括：1）开发用于生物样品的GAGactomes的解析的技术， 特别是骨髓的细胞和微环境; 2）使用合成的GAG模拟物文库 用于调节造血结果;和3）阐明GAG识别的特异性和功能， 唾液酸转移酶ST 6 Gal-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。特别是关于造血，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相互作用是选择性的吗？如果 选择性地，GAG序列或GAG的模拟物可以被利用作为造血障碍的治疗剂吗？ 总的来说，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 造血和血栓形成的过程。