Project 3: Role of Glycosaminoglycans in Hematopoiesis

项目3：糖胺聚糖在造血中的作用

基本信息

批准号：
10545019
负责人：
Umesh Ramanlal Desai
金额：
$ 58.96万
依托单位：
VERSITI WISCONSIN, INC.
依托单位国家：
美国
项目类别：
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/10545019
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 Glycobiology Glycosaminoglycans Goals Granulopoiesis Growth Factor Hematopoiesis Hematopoietic HepG2 In Vitro Knowledge Leg Length Leukocyte Elastase Libraries Macrophage Maintenance Mediating Megakaryocytes Molecular Nature Outcome Pathway interactions Peptide Hydrolases Physiological Polymers Polysaccharides Proliferating Proteins Proteoglycan Research Personnel Resort Role Sampling Screening procedure Specificity Structure Structure-Activity Relationship Sulfate Technology Therapeutic Thrombopoiesis Time Transferase Work design extracellular in vivo mimetics novel programs receptor response self-renewal sialylation tool

项目摘要

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 (GAG) 有助于多种且常常相反的功能，例如细胞功能然而，人们对增殖和凋亡、自我更新和分化知之甚少。诱导这些功能的确切 GAG 序列对于该计划项目特别重要。 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知之甚少。阐明对造血和血小板生成具有重要意义的 GAG 结构-功能关系。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；以及 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。该项目旨在回答诱导造血功能的 GAG。 GAG 是否调节造血细胞命运的问题如果是的话，GAG 相互作用是否具有选择性？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。