Endothelial Cell Phenotypes in Health and Disease

健康和疾病中的内皮细胞表型

基本信息

批准号：
8697092
负责人：
William C Aird
金额：
$ 203.51万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8697092
关键词：
Address Advisory Committees Alberta province Area Award Azacitidine Biological Assay Biology Blood Circulation Blood Vessels Cell Differentiation process Cell physiology Characteristics Collaborations Complementary DNA Country Cues DNA Methylation DNA Methyltransferase Inhibitor Data Development Disease E-Selectin Endothelial Cells Endothelium Environment Enzymes Epigenetic Process Foundations Functional RNA Funding Gene Expression Gene Expression Regulation Gene Targeting Genes Genetic Goals Grant Health Health Sciences Heterogeneity Histone Deacetylase Inhibitor Histones Human Human Development Hypoxia Individual Inherited Institutes Institution Lead Lesion Mediating Mediator of activation protein Messenger RNA MicroRNAs Mission Modeling Modification Molecular Morbidity - disease rate Mus Nature Ocular orbit Organ Paper Phenotype Poly A Population Principal Investigator Process Publishing RNA Recovery Recruitment Activity Regulation Relative (related person)Repression Research Research Personnel Resources Role Scientist Seminal Sepsis Site Smooth Muscle Myocytes Stem cells Talents Technical Expertise Techniques Technology Time Tissues Transcriptional Regulation Trees Trichostatin A Umbilical vein United States Universities Vascular Diseases Vascular Endothelial Growth Factor Receptor-2 Western World Wisconsin Writing base cadherin 5 cell type chromatin remodeling embryonic stem cell experience extracellular histone modification human NOS3 protein inhibitor/antagonist insight interdisciplinary approach interest medical schools meetings member mortality new technology novel therapeutics programs promoter success text searching tool transcription factor vascular bed von Willebrand Factor

项目摘要

Vascular diseases are among the most common causes of morbidity and mortality in the Western world. A remarkable feature of these disorders is the local nature of their distribution; virtually all diseases are associated with focal pathological lesions in characteristic sites of the vascular tree. A key to understanding the mechanisms of focal vasculopathy is found within the endothelium. Endothelial cell (EC) phenotypes are differentially regulated in space and time. Phenotypic heterogeneity is governed largely at the level of gene expression. The integrating theme of this program is that cis-trans and epigenetics contribute to lineage determination and EC heterogeneity. The overall goal is to apply multidisciplinary approaches, including cutting-edge epigenetic assays, gene targeting, embryoid body differentiation assays, flow models and sepsis models to dissect the relative contribution of cis-trans and epigenetic forces in mediating lineage- and vascular bed-specific endothelial gene expression and phenotypes. The PPG integrates investigators with diverse expertise required to advance our understanding of gene regulation in the endothelium. Project 1 ("Spatial and temporal dynamics of von Willebrand factor (vWF) gene expression"; William C. Aird, Project Leader) focuses on molecular mechanisms governing vWF expression in health and disease. Project 2 ("Transcriptional regulation of endothelial differentiation by ERG"; Peter Oettgen, Project Leader) explores the role of the ETS transcription factor ERG in the regulation of EC differentiation, vascular development, and human endothelial progenitor cell function. Project 3 ("Endothelial lineage diversity: role of epigenetics"; Philip Marsden, Project Leader) examines the role of epigenetic forces in mediating endothelial cell-specific gene expression of eNOS. Core A ("Administrative Support"; William C. Aird, Core Leader) provides standard administrative support, including the coordination of all applicable statutory compliance, for the Program. Core B ("Epigenetics Core"; John Whetstine, Core Leader) provides expertise and technical support for studying epigenetic modification of endothelial genes. Core C ("Gene Targeting Core"; William C. Aird, Core Leader) provides the necessary tools for targeting the Hprt locus and the loci of endogenous genes in ES cells and mice.

血管疾病是西方世界中发病和死亡率最常见的原因之一。这些疾病的一个了不起的特征是它们分布的局部性质。几乎所有疾病都与血管树特征部位的局灶性病变病变有关。在内皮中发现了了解局灶性血管病的机制的关键。内皮细胞（EC）表型在空间和时间上受到差异调节。表型异质性在很大程度上受到基因表达水平的控制。该程序的综合主题是顺式传播和表观遗传学有助于谱系确定和EC异质性。总体目标是采用多学科方法，包括尖端的表观遗传测定，基因靶向，胚胎身体分化测定，流程模型和败血症模型，以剖析介导谱系和血管性底型内皮细胞基因表达和均具有相对贡献的相对贡献。 PPG将研究人员与需要多样化的专业知识相结合，以促进我们对内皮中基因调节的理解。项目1（“ von Willebrand因子（VWF）基因表达的空间和时间动力学”；项目负责人William C. Aird）着重于控制VWF健康和疾病中VWF表达的分子机制。项目2（“通过ERG对内皮分化的转录调节”；项目负责人Peter Oettgen）探讨了ETS转录因子ERG在EC分化，血管发育和人类内皮祖细胞功能的调节中的作用。项目3（“内皮谱系多样性：表观遗传学的作用”；项目负责人菲利普·马斯登（Philip Marsden）研究表观遗传力在介导eNOS的内皮细胞特异性基因表达中的作用。核心A（“行政支持”；核心负责人威廉·C·艾尔德（William C. Aird）提供了标准的行政支持，包括该计划的所有适用法定合规性的协调。 Core B（“表观遗传学核心”；核心负责人John Whetstine）为研究内皮基因的表观遗传学修饰提供了专业知识和技术支持。 Core C（“基因靶向核心”； William C. Aird，核心负责人）提供了靶向HPRT基因座和ES细胞和小鼠内源基因基因座的必要工具。

项目成果

期刊论文数量（55）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Bone marrow cell therapies for endothelial repair and their relevance to kidney disease.

用于内皮修复的骨髓细胞疗法及其与肾脏疾病的相关性。

DOI：
10.1016/j.semnephrol.2012.02.008
发表时间：
2012
期刊：
Seminars in nephrology
影响因子：
3.3
作者：
Yuen,DarrenA;Gilbert,RichardE;Marsden,PhilipA
通讯作者：
Marsden,PhilipA

ERG is required for the differentiation of embryonic stem cells along the endothelial lineage.

DOI：
10.1186/1471-213x-9-72
发表时间：
2009-12-23
期刊：
BMC developmental biology
影响因子：
0
作者：
Nikolova-Krstevski V;Yuan L;Le Bras A;Vijayaraj P;Kondo M;Gebauer I;Bhasin M;Carman CV;Oettgen P
通讯作者：
Oettgen P

Angiogenesis in glioblastoma.