Pathway maps of platelet phenotype and function

血小板表型和功能的通路图

基本信息

批准号：
10599257
负责人：
JOSEPH E ASLAN
金额：
$ 38.5万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10599257
关键词：
Acceleration Address Adhesions Adhesives Affect Agonist Alpha Granule Atherosclerosis Biochemical Biological Blood Cells Blood Platelets Cardiovascular Diseases Cause of Death Cell model Cell-Cell Adhesion Cells Chronic Disease Coagulation Process Complement Complex Cues Cytokine Receptors Cytoplasmic Granules Cytoskeleton Data Disease Endothelium Event Filopodia Glycoproteins Goals Hemorrhage Hemostatic Agents Hemostatic function Image Inflammation Inflammatory Inflammatory Response Injury Integrins Knowledge Leukocytes Maps Measurement Measures Mediating Mediator Methodology Methods Modeling Molecular Morbidity - disease rate Output P-Selectin Pathogenesis Pathway interactions Phenotype Phospholipase Phosphorylation Physiological Platelet Activation Process Proteins Proteomics Public Health Purinoceptor Receptor Signaling Regulation Role Signal Pathway Signal Transduction Site Specific qualifier value System Systems Biology Testing Thrombosis Work adhesion receptor disability extracellular improved in vivo mortality novel platelet function platelet phenotype prevent programs receptor release factor response thrombotic tool trafficking translatable strategy vascular inflammation

项目摘要

PROJECT SUMMARY As the primary cellular mediators of hemostasis, platelets are optimized to limit bleeding through rapid adhesion, secretion and aggregation responses at sites of endothelial injury. Platelets also adhere to dysfunctional endothelium, where they secrete proinflammatory molecules and form aggregates with leukocytes to progress vascular inflammation in a manner relevant to the pathogenesis of chronic diseases, including atherosclerosis. Ongoing efforts aiming to understand and target platelet activities specific to disease have characterized a spectrum of platelet functional phenotypes associated with inflammatory, thrombotic and other conditions. Despite the identification of key molecular alterations that highlight differences between these phenotypes, it remains unclear how different platelet phenotypes develop, how they should be defined, and, ultimately, how they should be targeted. We hypothesize that platelet hemostatic, inflammatory and other phenotypes are determined by the systematic activation of intracellular signaling pathways and effectors that result in specific platelet functional outputs in response to physiological context. We aim to systematically define intracellular signaling events that progress platelet adhesion (Aim 1), secretion (Aim 2) and aggregation (Aim 3) in hemostatic programs and to determine how these responses mechanistically differ in the context of vascular inflammation. We will engage these studies through the use of a high-throughput, proteomics-based workflow that measures and maps intracellular signaling events and pathways underlying platelet function in specific experimental and physiological contexts. We now use this set of proteomics, computational and cell biological tools to build pathway maps intracellular signaling relations in platelet activation programs. In this proposal, we use this first-in-class pathway mapping methodology together with other physiological and systems biology tools to address how platelet signaling programs specify platelet phenotypes favoring hemostatic and inflammatory responses. Ultimately, this work will generate knowledge as well as a conceptual means to define and understand systems level mechanisms of platelet regulation in hemostasis as well as in inflammation and the manifestation of disease.

项目概要作为止血的主要细胞介质，血小板被优化以通过快速止血来限制出血。内皮损伤部位的粘附、分泌和聚集反应。血小板也粘附在功能失调的内皮，它们分泌促炎分子并与白细胞以与慢性疾病发病机制相关的方式进展血管炎症，包括动脉粥样硬化。正在进行的努力旨在了解和针对疾病特有的血小板活性已经表征了与炎症、血栓形成和相关的一系列血小板功能表型其他条件。尽管识别出关键的分子改变突出了这些之间的差异表型，目前尚不清楚不同的血小板表型如何发展，如何定义它们，以及，最终，他们应该如何定位。我们假设血小板具有止血、抗炎和其他作用表型是由细胞内信号通路和效应器的系统激活决定的导致响应生理环境的特定血小板功能输出。我们的目标是系统地定义促进血小板粘附（目标 1）、分泌（目标 2）和聚集的细胞内信号传导事件（目标 3）在止血程序中，并确定这些反应在机制上有何不同血管炎症。我们将通过使用高通量、基于蛋白质组学的方法来开展这些研究测量和绘制血小板功能背后的细胞内信号事件和通路的工作流程特定的实验和生理背景。我们现在使用这套蛋白质组学、计算和细胞构建血小板激活程序中细胞内信号传导关系通路图的生物工具。在这个建议，我们将这种一流的路径图谱方法与其他生理学和系统生物学工具可解决血小板信号传导程序如何指定有利于血小板表型的问题止血和炎症反应。最终，这项工作将产生知识和概念是指定义和理解止血和血小板调节的系统水平机制。炎症和疾病的表现。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Novel disintegrin-like peptides derived from an amphibian skin cDNA sequence of Hypsiboas punctatus.

源自 Hypsiboas punctatus 两栖动物皮肤 cDNA 序列的新型解整合素样肽。

DOI：
发表时间：
2022-05
期刊：
影响因子：
0
作者：
Pires, Diego A T;Tacca, Luisa M R A;Aslan, Joseph E;Murad, André M;Nascimento, Claudia J;Barbosa, Eder A;Bloch Jr, Carlos
通讯作者：
Bloch Jr, Carlos

Platelet reactivity and platelet count in women with iron deficiency treated with intravenous iron.

接受静脉补铁治疗的缺铁女性的血小板反应性和血小板计数。

DOI：
发表时间：
2022-02
期刊：
影响因子：
0
作者：
Elstrott, Benjamin K;Lakshmanan, Hari H S;Melrose, Alexander R;Jordan, Kelley R;Martens, Kylee L;Yang, Chih;Peterson, Danielle F;McMurry, Hannah Stowe;Lavasseur, Corinne;Lo, Jamie O;Olson, Sven R;DeLoughery, Thomas G;Aslan, Joseph E;Shatz
通讯作者：
Shatz

Perspectives on Platelet Heterogeneity and Host Immune Response in Coronavirus Disease 2019 (COVID-19).

2019 年冠状病毒病 (COVID-19) 中血小板异质性和宿主免疫反应的观点。

DOI：
发表时间：
2020-10
期刊：
影响因子：
5.7
作者：
Parra;Aslan, Joseph E
通讯作者：
Aslan, Joseph E

Different strokes, different thrombus proteomes.

不同的中风，不同的血栓蛋白质组。

DOI：
发表时间：
2023-10
期刊：
影响因子：
0
作者：
Aslan; Joseph E
通讯作者：
Joseph E

A Sample Preparation Protocol for High Throughput Immunofluorescence of Suspension Cells on an Adherent Surface.

粘附表面悬浮细胞高通量免疫荧光的样品制备方案。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Bäckström, Anna;Kugel, Laura;Gnann, Christian;Xu, Hao;Aslan, Joseph E;Lundberg, Emma;Stadler, Charlotte
通讯作者：
Stadler, Charlotte