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.

项目摘要了解损伤后的组织愈合和蛋白质表达在再生医学中至关重要。这糖蛋白CTHRC1在组织修复，脂肪细胞形成和骨发育中起着至关重要的作用。它是由活化的成纤维细胞产生的，并有助于代谢效率和内皮细胞的存活，在康复过程中维持体内稳态和毛细血管网络。但是，异常的CTHRC1表达是在慢性炎症和恶性生长中观察到。而糖基化对于适当的许多分泌蛋白的功能，我们尚不了解糖基化如何影响有益作用 CTHRC1。 CTHRC1是一种分泌的蛋白质，其N末端为16-氨基酸促肽。删除此促肽增加蛋白质的生物学活性。我们最近的发现表明全长 CTHRC1的截短形式促进内皮细胞中的糖酵解，截短的形式尤其是潜在的。即使这些初始的结构活性观测突出了蛋白质修饰的重要性在控制CTHRC1的活动时，没有进一步的研究探讨结构与功能之间的关系已经进行了CTHRC1。另外，CTHRC1的特定接收器仍然未知。在这个协作项目，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及其在控制能量代谢中的作用。我们还将跟踪内部化CTHRC1的细胞定位通过化学标记不同的氨基酸以阐明其作用部位。了解亲糖酵解 CTHRC1的影响有助于理解持续组织中内皮细胞的功能维修。该建议旨在将CTHRC1开发为有价值的工具，以更好地了解伤口愈合过程中激活的内皮细胞。为了实现这一目标，我们将采用跨学科团队科学方法以生物医学研究中心的专业知识和资源为基础在密西西比州和缅因州的Nigms支持的卓越（鞋底）。通过利用最先进的糖性技术，我们旨在应对再生医学领域所面临的挑战。

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）

Assessment of Evolutionary Relationships for Prioritization of Myxobacteria for Natural Product Discovery.

DOI：
10.3390/microorganisms9071376
发表时间：
2021-06-24
期刊：
Microorganisms
影响因子：
4.5
作者：
Ahearne A;Albataineh H;Dowd SE;Stevens DC
通讯作者：
Stevens DC

Inhibition of SARS-CoV-2 wild-type (Wuhan-Hu-1) and Delta (B.1.617.2) strains by marine sulfated glycans.

DOI：
10.1093/glycob/cwac042
发表时间：
2022-09-19
期刊：
Glycobiology
影响因子：
4.3
作者：
通讯作者：

Red Algal Sulfated Galactan Binds and Protects Neural Cells from HIV-1 gp120 and Tat.

DOI：
10.3390/ph14080714
发表时间：
2021-07-23
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
0
作者：
Pomin VH;Mahdi F;Jin W;Zhang F;Linhardt RJ;Paris JJ
通讯作者：
Paris JJ

Antiviral activity of marine sulfated glycans against pathogenic human coronaviruses.

DOI：
10.1038/s41598-023-31722-5
发表时间：
2023-03-23
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
Zoepfl, Mary;Dwivedi, Rohini;Kim, Seon Beom;McVoy, Michael A.;Pomin, Vitor H.
通讯作者：
Pomin, Vitor H.

Functional genomics study of Pseudomonas putida to determine traits associated with avoidance of a myxobacterial predator.