Project 3: Role of Glycosaminoglycans in Hematopoiesis

项目3：糖胺聚糖在造血中的作用

• 批准号: 10088970
• 负责人: Umesh Ramanlal Desai
• 金额: $ 59.97万
• 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/10088970
• 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 - 项目摘要/摘要 糖胺聚糖（插科打）有助于无数且经常相反的功能，例如细胞 增殖以及凋亡，自我更新和分化。然而，宝贵的理解很少 影响这些功能的确切GAG序列。对于这个程序项目特别重要，尽管 插科打术是骨髓（BM）微环境的重要组成部分 插科打调节造血细胞命运；这些相互作用是选择性/特定的；以及插科打还是 为治疗目的可以利用类似插科打的分子。这个项目集中在 阐明重要性与造血和血小板的插科打结构 - 功能关系。三 提出了目标，包括1）开发技术来阐明生物样品的肠胃乳突， 尤其是骨髓的细胞和微环境； 2）雇用合成插科打的库 用于调节造血结果； 3）阐明插科打识别的特异性和功能 siAlyl转移酶ST6GAL-1。这些目标的结果将是精确的结构 - 功能关系 影响造血功能的堵嘴。该项目旨在回答 插科打s的问题是否调节造血细胞命运。如果是这样，GAG交互是选择性的吗？如果 有选择性，插科打s序列或模拟物可以用作造血疾病的治疗吗？ 总体而言，该项目在该地区贡献知识，工具/技术和热有前途的代理商 造血和血栓形成。