GlyCORE: Glycoscience Center of Research Excellence

GlyCORE：糖科学卓越研究中心

基本信息

批准号：
10853237
负责人：
SAMIR A ROSS
金额：
$ 47.49万
依托单位：
UNIVERSITY OF MISSISSIPPI
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-15 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10853237
关键词：
Address Adipocytes Adopted Affect Amino Acids Analytical Chemistry Binding Biological Biological Assay Biological Process Biology Biomedical Research Blood capillaries Bone Development Carbohydrates Cell Culture Techniques Cell Survival Cell physiology Cells Cellular biology Centers of Research Excellence Characteristics Chemicals Chronic Collaborations Collagen Collagen Receptors Confocal Microscopy Core Facility Data Endothelial Cells Energy Metabolism Enzyme-Linked Immunosorbent Assay Evaluation Faculty Fibroblasts Fluorine Foundations Funding Genus Hippocampus Glycolysis Glycoproteins Goals Growth Health Histopathology Homeostasis Human Image Inflammation Injury Label Laboratories Length Link Maine Malignant - descriptor Malignant Neoplasms Mass Spectrum Analysis Mediator Mentors Metabolic Metabolism Mississippi Mitochondria Modification N-terminal NMR Spectroscopy National Institute of General Medical Sciences Nature Osteogenesis Pharmaceutical Chemistry Play Post-Translational Protein Processing Process Protein Secretion Proteins Recombinants Regenerative Medicine Regulation Research Research Institute Research Personnel Research Project Grants Resources Respiration Role Science Site Structure Structure-Activity Relationship System Techniques Therapeutic Uses Tissues Umbilicus Universities Variant Work biophysical chemistry career clinical translation experience glycosylated collagen glycosylation healing interdisciplinary approach lipid biosynthesis meetings metabolic abnormality assessment protein expression recruit stem stem cells synergism tissue injury tissue repair tool translational potential triple helix wound healing

项目摘要

Project Summary Understanding tissue healing and protein expression after injury is crucial in regenerative medicine. The glycoprotein CTHRC1 plays a vital role in tissue repair, regulation of fat cell formation, and bone development. It is produced by activated fibroblasts and contributes to metabolic efficiency and the survival of endothelial cells, which maintain homeostasis and capillary networks during healing. However, abnormal CTHRC1 expression is observed in chronic inflammation as well as malignant growth. While glycosylation is essential for the proper functioning of many secreted proteins, we don't yet understand how glycosylation impacts the beneficial effects of CTHRC1. CTHRC1 is a secreted protein with a 16-amino acid pro-peptide at its N-terminus. Removing this pro-peptide increases the biological activity of the protein. Our recent findings indicate that both the full-length and truncated forms of CTHRC1 promote glycolysis in endothelial cells, with the truncated form being particularly potent. Even though these initial structure–activity observations highlight the importance of protein modifications in controlling activity of CTHRC1, no further studies exploring the relationship between structure and function of CTHRC1 have been conducted. Additionally, the specific receptor for CTHRC1 remains unknown. In this collaborative project, our goal is to investigate how glycosylation of CTHRC1 influences its binding to target cells and its role in regulating energy metabolism. We will also track the cellular localization of internalized CTHRC1 by chemically tagging different amino acid residues to elucidate its site of action. Understanding the pro-glycolytic effects of CTHRC1 is instrumental in comprehending the functioning of endothelial cells during ongoing tissue repair. This proposal aims to develop CTHRC1 into a valuable tool to better understand the characteristics of activated endothelial cells during wound healing. To accomplish this objective, we will adopt an interdisciplinary team-science approach that builds upon the expertise and resources of the Centers for Biomedical Research Excellence (COBRE) supported by NIGMS in Mississippi and Maine. By leveraging state-of-the-art glycoscience techniques, we aim to address the challenges faced in the field of regenerative medicine.

项目概要了解损伤后的组织愈合和蛋白质表达对于再生医学至关重要。糖蛋白 CTHRC1 在组织修复、脂肪细胞形成调节和骨骼发育中发挥着至关重要的作用。它由活化的成纤维细胞产生，有助于代谢效率和内皮细胞的存活，然而，CTHRC1 表达异常。在慢性炎症和恶性生长中观察到，而糖基化对于正常的正常生长至关重要。许多分泌蛋白的功能，我们还不了解糖基化如何影响有益效果 CTHRC1 是一种分泌蛋白，其 N 末端有一个 16 个氨基酸的前肽。我们最近的研究结果表明，前肽增加了蛋白质的生物活性。 CTHRC1 的截短形式促进内皮细胞中的糖酵解，尤其是截短形式尽管这些最初的结构-活性观察强调了蛋白质修饰的重要性。在控制CTHRC1的活性方面，没有进一步的研究探索其结构和功能之间的关系此外，CTHRC1 的特异性受体仍未知。合作项目，我们的目标是研究 CTHRC1 的糖基化如何影响其与靶细胞的结合我们还将追踪内化 CTHRC1 的细胞定位。通过化学标记不同的氨基酸残基来阐明其促糖酵解的作用位点。 CTHRC1 的作用有助于理解正在进行的组织过程中内皮细胞的功能该提案旨在将 CTHRC1 开发成一个有价值的工具，以更好地了解修复的特征。为了实现这一目标，我们将采用跨学科的方法。基于生物医学研究中心的专业知识和资源的团队科学方法 Excellence (COBRE) 得到密西西比州和缅因州 NIGMS 的支持，利用最先进的糖科学。技术，我们的目标是解决再生医学领域面临的挑战。

项目成果

期刊论文数量（47）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Selective 2-desulfation of tetrasaccharide-repeating sulfated fucans during oligosaccharide production by mild acid hydrolysis.

在低聚糖生产过程中，通过弱酸水解对四糖重复硫酸化岩藻聚糖进行选择性 2-脱硫。

DOI：
发表时间：
2023-02-01
期刊：
影响因子：
11.2
作者：
Kim, Seon Beom;Farrag, Marwa;Mishra, Sushil K;Misra, Sandeep K;Sharp, Joshua S;Doerksen, Robert J;Pomin, Vitor H
通讯作者：
Pomin, Vitor H

Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2.

人 Dectin-1 是 O-糖基化的，可作为 C 型凝集素受体 CLEC-2 的配体。

DOI：
发表时间：
2022-12-08
期刊：
影响因子：
7.7
作者：
Haji, Shojiro;Ito, Taiki;Guenther, Carla;Nakano, Miyako;Shimizu, Takashi;Mori, Daiki;Chiba, Yasunori;Tanaka, Masato;Mishra, Sushil K;Willment, Janet A;Brown, Gordon D;Nagae, Masamichi;Yamasaki, Sho
通讯作者：
Yamasaki, Sho

Chromosomal organization of biosynthetic gene clusters, including those of nine novel species, suggests plasticity of myxobacterial specialized metabolism.

生物合成基因簇（包括九个新物种的基因簇）的染色体组织表明粘细菌专门代谢的可塑性。

DOI：
发表时间：
2023
期刊：
影响因子：
0
作者：
Ahearne, Andrew;Phillips, Kayleigh E;Knehans, Thomas;Hoing, Miranda;Dowd, Scot E;Stevens, David Cole
通讯作者：
Stevens, David Cole

Transient Formation of Hemiketals from Pentafluoro-gem-diols in the Presence of Alcohols.

在醇存在下由五氟宝石二醇瞬时形成半缩酮。

DOI：
10.1016/j.jfluchem.2023.110162
发表时间：
2023-08-01
期刊：
Journal of fluorine chemistry
影响因子：
1.9
作者：
Baharul Islam;David A. Colby
通讯作者：
David A. Colby

Generation of formaldehyde and formaldehyde-d2 for hydroxymethylations and hydroxydeuteromethylations of difluoroenolates and difluorobenzyl carbanions.

生成甲醛和甲醛-d2，用于二氟烯醇盐和二氟苄基碳负离子的羟甲基化和羟基氘甲基化。

DOI：
10.1039/d2cc01518h
发表时间：
2022-05-03
期刊：
Chemical communications
影响因子：
4.9
作者：
Khatri, Hari R.;Han, Changho;Alkhodier, Reem A.;Adam, Amna T.;Islam, Baharul;Colby, David A.
通讯作者：
Colby, David A.