Hyaluronan Matrices in Vascular Pathologies

血管病理学中的透明质酸基质

基本信息

批准号：
8669079
负责人：
VINCENT CHARLES HASCALL
金额：
$ 221.18万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8669079
关键词：
Adenosine Adhesives Anabolism Authorship Blood Platelets Blood Vessels Carbohydrates Cell membrane Cells Cellular Stress Chondroitin Sulfates Clinical Pathology Collaborations Complex Core Protein Cytosol Development Diabetes Mellitus Excision Extracellular Space Functional disorder Future Glucose Glycocalyx Glycosaminoglycans Goals Golgi Apparatus Heparin Heparitin Sulfate Hyaluronan Hyperglycemia Inflammation Inflammatory Inflammatory Bowel Diseases Inflammatory Response Investigation Keratan Sulfate Leadership Leukocytes Medical Students Methods Modification Paper Pathology Pathway interactions Postdoctoral Fellow Process Proteoglycan Pulmonary Hypertension Recruitment Activity Research Research Personnel Resource Sharing Role Signal Transduction Staining method Stains Structure Techniques Tissues Training Uncertainty Universities Uridine Diphosphate Sugars Vascular Diseases Visit Work Wound Healing base diabetic frontier graduate student hyaluronan synthase 1 macrophage meetings member monocyte novel programs research study response skills sugar

项目摘要

DESCRIPTION (provided by applicant): (Overview, Hascall) Program Introduction and Objectives - The 5 projects in our PEG, Hyaluronan Matrices in Vascular Pathologies, explore the emerging central role that hyaluronan (HA)-based matrices have in vascular development and inflammatory pathologies of the vasculature. Members of the Research Team have already collaborated and pioneered the initial research with this matrix and its dialogue with inflammatory cells. We now propose to focus in depth on novel investigations that further investigate the HA matrix and its interactions with leukocytes in vasculopathies related to diabetes (Project 1), wound healing (Project 2), inflammatory bowel disease (Project 3), pulmonary hypertension (Project 4), and glycocalyx/pericellular matrix modification in vascular development (Project 5). The existing synergy of the Research Team is established by the co-authorship of papers in the biosketches, by new collaborations, and by the crosstalk between the aims of the projects and the methods employed. During the course of the PEG, each project will recruit two junior investigators (graduate student, medical student, or postdoctoral fellow) who will receive glycoscience and glycotechnology training through the enrichment course described in the Glycosciences Skills Development Core C and by attending courses at the Complex Carbohydrate Research Center at the University of Georgia. Shared Resource Core B will provide all projects with comprehensive analyses to determine the amounts, sizes, fine structures, and modifications of glycosaminoglycans, and will prepare tissues for sectioning and staining for HA and relevant matrix molecules. Shared Resource Core B will work with Glycosciences Skills Development Core C to provide training for the junior investigators in these techniques with emphasis on their project-related experiments. The Administration Core will provide overall leadership for the PEG and coordinate the biweekly meetings of the investigators in the Research Teams to discuss ongoing experimental results and plan future experiments. Biannual meetings of the Internal Advisory Board, and visits by the Visiting Scholars and members of an External Advisory Board will review progress, provide project guidance, and enrich scholarly activities within the PEG. RELEVANCE: Vascular tissues and circulating leukocytes are involved in essentially all inflammatory processes. Thus, understanding the mechanisms involved in synthesizing the monocyte-adhesive hyaluronan matrix and the responses of inflammatory cells that interact with it, offers to provide a central paradigm for most inflammatory processes and subsequent pathologies.

描述（由申请人提供）：（概述，Hascall）项目简介和目标 - 我们的 PEG（血管病理学透明质酸基质）中的 5 个项目探索基于透明质酸 (HA) 的基质在血管发育和炎症病理学中的新兴核心作用脉管系统的。研究团队的成员已经合作并开创了对该基质及其与炎症细胞对话的初步研究。我们现在建议深入关注新的研究，进一步研究与糖尿病（项目 1）、伤口愈合（项目 2）、炎症性肠病（项目 3）、肺动脉高压（项目）相关的血管病变中的 HA 基质及其与白细胞的相互作用4），以及血管发育中的糖萼/细胞周基质修饰（项目 5）。研究团队现有的协同作用是通过生物草图中论文的共同作者、新的合作以及项目目标和所采用的方法之间的相互影响而建立的。在 PEG 课程期间，每个项目将招募两名初级研究员（研究生、医学生或博士后），他们将通过糖科学技能发展核心 C 中描述的强化课程以及参加佐治亚大学复杂碳水化合物研究中心。共享资源核心B将为所有项目提供全面的分析，以确定糖胺聚糖的数量、大小、精细结构和修饰，并准备组织用于HA和相关基质分子的切片和染色。共享资源核心 B 将与 Glycosciences 技能开发核心 C 合作，为初级研究人员提供这些技术方面的培训，重点是他们的项目相关实验。管理核心将为 PEG 提供全面领导，并协调研究团队中研究人员每两周一次的会议，讨论正在进行的实验结果并规划未来的实验。内部顾问委员会每年两次的会议以及访问学者和外部顾问委员会成员的访问将审查进展情况，提供项目指导，并丰富 PEG 内的学术活动。相关性：血管组织和循环白细胞基本上参与所有炎症过程。因此，了解合成单核细胞粘附性透明质酸基质所涉及的机制以及与其相互作用的炎症细胞的反应，可以为大多数炎症过程和随后的病理学提供中心范例。