CardioPulmonary Vascular Biology COBRE

心肺血管生物学 COBRE

• 批准号: 10854140
• 负责人: Gaurav Choudhary
• 金额: $ 109.16万
• 依托单位: OCEAN STATE RESEARCH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10854140
• 关键词: Address; Affect; Applications Grants; Area; Arkansas; Arrhythmia; Artificial Intelligence; Award; Bioenergetics; Biological Assay; Biology; Blood Vessels; Cardiac Myocytes; Cardiac Output; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular system; Cell Separation; Centers of Research Excellence; Collaborations; Communities; Compensation; Core Facility; Data; Data Science; Data Set; Development; Dimensions; Discipline; Disease; Doctor of Philosophy; Engineering; Evaluation; Experimental Designs; Extracellular Matrix; Failure; Fibrosis; Fostering; Functional disorder; Funding; Goals; Heart Atrium; Heart failure; Heterogeneity; Home; Hospitals; Human; Infrastructure; Institution; Investigation; Kentucky; Knowledge; Lung; Lung diseases; Mathematics; Mechanics; Mediator; Medicine; Metabolic; Metabolic Diseases; Metabolic dysfunction; Methodology; Mission; Mitochondria; Molecular; Morbidity - disease rate; Myocardial; Myocardium; New Hampshire; Oceans; Organ; Outcome; Parents; Pathogenesis; Pathway interactions; Pharmacy facility; Phase; Phenotype; Pilot Projects; Population; Pre-Clinical Model; Prevention; Productivity; Prognosis; Program Research Project Grants; Proteomics; Pulmonary Heart Disease; Pulmonary Hypertension; Research; Research Institute; Research Personnel; Research Project Grants; Resources; Rhode Island; Right Ventricular Dysfunction; Right Ventricular Function; Role; Science; Scientist; Services; Severities; Signal Pathway; Signal Transduction; Techniques; Therapeutic; Time; Universities; Vascular Diseases; Ventricular; Ventricular Remodeling; Vision; Work; catalyst; cell type; combat; comorbidity; effective therapy; experimental study; hemodynamics; human tissue; in vivo imaging; insight; inter-institutional; metabolomics; mortality; multidisciplinary; multimodality; multiple omics; neural network; novel; prevent; programs; pulmonary vascular remodeling; response; right ventricular failure; synergism; targeted treatment; transcriptome sequencing; transcriptomics; ventricular hypertrophy

Cardiopulmonary Vascular Biology COBRE Team Science Supplement Project Summary: Goal of the parent award: The vision of the CardioPulmonary Vascular Biology (CPVB) COBRE program is to develop effective approaches to prevent and treat vascular diseases affecting the pulmonary and cardiovascular systems through better understanding of disease mechanisms. This is accomplished by serving as an interdisciplinary center which promotes collaborative research and provides excellent technical support and resources to investigators. The overall mission of the CPVB COBRE program has been to build the human and technical infrastructure and services that serve as catalysts to increase CPVB research in the state. Cardiovascular and pulmonary diseases are among the leading causes of morbidity and mortality in the US and in the world. Thus, there is an important need to understand the pathogenesis of cardiopulmonary vascular diseases in order to develop more effective treatments and prevention. The overall goal of the CPVB COBRE program is to facilitate high impact vascular biology research. The CPVB COBRE program provides infrastructure with administrative, pilot project, and two technical cores, thus providing opportunities to expand areas of investigation, experimental and technical approaches, and scientific collaborations. The specific aims of Phase III CPVB COBRE are to: i) award high-impact research projects in the area of cardiopulmonary vascular biology; ii) provide effective and high-quality services in cell isolation and ex vivo organ function (CIOF), mitochondrial function, and in vivo imaging (MF-II); iii) collaborate with IDeA programs in Rhode Island (RI) and other states to foster scientific networks by providing programming, funding, technical services, and resources to enhance research productivity; and iv) maintain a robust line of investigation in vascular biology that meets the needs of the scientific community and furthers research in prevention and treatment of cardiopulmonary vascular diseases. We will expand and enrich the vascular biology research community by promoting new collaborations and engaging scientists new to the field from a variety of disciplines. At the end of Phase III, we expect to transition to a sustainable CPVB Center serving as a home to the CVPB research community with high quality core services, significant institutional support, and commitment to continue the development of effective approaches to combat or resolve cardiopulmonary vascular diseases. Research question to be addressed by the supplement award: Right Ventricular (RV) dysfunction in settings of pulmonary hypertension (PH) is associated with poor outcomes irrespective of associated comorbidities and underlying conditions. PH is common and afflicts ~ 1 % of world population, is commonly associated with cardiopulmonary diseases, and in many cases is associated with pulmonary vascular remodeling. Despite the known poor prognosis associated with RV dysfunction, to date, no RV targeted therapies are available, and the underlying mechanisms of RV dysfunction remain unclear. Therefore, there is an unmet need for a better understanding of cellular and molecular mechanisms associated with RV dysfunction and to convert this knowledge into therapies. Pathophysiological mechanisms associated with RV dysfunction include changes in cellular composition of the myocardium, matrix remodeling (e.g., fibrosis), metabolic dysfunction resulting in heart failure and ventricular and atrial arrhythmias. While reductionist approaches have resulted in important insights into role of specific cell types and signaling pathways, a comprehensive evaluation using multi-scale and multi- omics evaluation and use of novel data-science analytical techniques to identify the networks and pathways that underlie maladaptive RV and RV dysfunction has not been performed and is the overall objective of this proposal. Why need for team science effort? Considering the multiple pathophysiological mechanisms, cell types and phenotypes (arrhythmia, energetic and mechanical failure) associated with RV dysfunction, there is need to bring together experts in myocardial biology, mitochondrial biology, and arrhythmia biology. Furthermore, use of large unbiased datasets to unravel novel networks and pathways underlying RV dysfunction requires analytical and methodological expertise in reducing the dimensionality of data and identification of important multi-omic network features using novel artificial intelligence based methodology that relate with the maladaptive phenotypes in settings of RV dysfunction. These data, approaches and collaborations are expected to result in multi-PI and program project grant applications that will lead to sustainable teams to perform impactful scientific investigation in cardiopulmonary vascular diseases such as RV dysfunction and failure.

心肺血管生物学 COBRE 团队科学补充项目摘要： 家长奖的目标：心肺血管生物学 (CPVB) COBRE 计划的愿景是 开发有效的方法来预防和治疗影响肺部和心血管的血管疾病 通过更好地了解疾病机制来建立系统。这是通过充当 跨学科中心，促进合作研究并提供卓越的技术支持和 调查人员的资源。 CPVB COBRE 计划的总体使命是建设人类和 技术基础设施和服务，作为增加该州 CPVB 研究的催化剂。 心血管和肺部疾病是美国和美国发病率和死亡率的主要原因之一 在世界上。因此，了解心肺血管疾病的发病机制非常重要。 以便开发出更有效的治疗和预防方法。 CPVB COBRE 的总体目标 该计划旨在促进高影响力的血管生物学研究。 CPVB COBRE 计划提供基础设施 具有行政、试点项目和两个技术核心，从而提供了扩大领域的机会 调查、实验和技术方法以及科学合作。阶段的具体目标 III CPVB COBRE 将： i) 授予心肺血管生物学领域的高影响力研究项目； ii) 在细胞分离和离体器官功能（CIOF）、线粒体 功能和体内成像（MF-II）； iii) 与罗德岛州 (RI) 和其他州的 IDeA 项目合作 通过提供规划、资金、技术服务和资源来促进科学网络的发展 研究生产力； iv) 维持血管生物学领域的强大研究路线，以满足以下需求： 科学界并进一步研究心肺血管的预防和治疗 疾病。我们将通过促进新的合作来扩大和丰富血管生物学研究界 并吸引来自不同学科领域的新科学家。在第三阶段结束时，我们预计 过渡到可持续的 CPVB 中心，作为高质量 CVPB 研究社区的家园 核心服务、重要的机构支持以及继续开发有效的 对抗或解决心肺血管疾病的方法。 补充奖要解决的研究问题：右心室（RV）功能障碍 肺动脉高压（PH）与不良预后相关，无论相关合并症和 基础条件。 PH 很常见，困扰着约 1% 的世界人口，通常与 心肺疾病，并且在许多情况下与肺血管重塑有关。尽管 已知与右心室功能障碍相关的不良预后，迄今为止，尚无可用的右心室靶向治疗，并且 RV 功能障碍的潜在机制仍不清楚。因此，对于更好的需求尚未得到满足 了解与 RV 功能障碍相关的细胞和分子机制，并将其转化为 将知识转化为治疗方法。与右心室功能障碍相关的病理生理机制包括 心肌的细胞组成、基质重塑（例如纤维化）、导致心脏的代谢功能障碍 衰竭以及室性和房性心律失常。虽然还原论方法已经产生了重要的见解 深入研究特定细胞类型和信号通路的作用，采用多尺度、多维度的综合评估 组学评估和使用新颖的数据科学分析技术来识别网络和途径 右心室适应不良和右心室功能障碍的基础尚未进行，这是该提案的总体目标。 为什么需要团队科学努力？考虑到多种病理生理机制、细胞类型和 与右心室功能障碍相关的表型（心律失常、精力和机械衰竭），需要携带 心肌生物学、线粒体生物学和心律失常生物学领域的专家齐聚一堂。此外，使用大 揭示 RV 功能障碍背后的新网络和通路的无偏见数据集需要分析和 降低数据维度和识别重要多组学网络的方法学专业知识 使用新颖的基于人工智能的方法来描述与适应不良表型相关的特征 RV 功能障碍的设置。这些数据、方法和协作预计将产生多 PI 和 计划项目拨款申请将导致可持续团队进行有影响力的科学研究 心肺血管疾病，如右心室功能障碍和衰竭。