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.

心肺血管生物学鞋布团队科学补充项目摘要： 父母奖的目标：心肺血管生物学（CPVB）的愿景是cobre计划 开发有效的方法来预防和治疗影响肺和心血管的血管疾病 通过更好地理解疾病机制的系统。这是通过担任的 跨学科中心促进合作研究并提供出色的技术支持和 资源向调查人员。 CPVB COBRE计划的整体使命是建立人类和 作为增加该州CPVB研究的催化剂的技术基础设施和服务。 心血管疾病和肺部疾病是美国发病率和死亡率的主要原因之一， 在世界上。因此，重要的需要了解心肺血管的发病机理 疾病以开发更有效的治疗和预防。 CPVB Cobre的总体目标 计划是为了促进高影响力血管生物学研究。 CPVB COBRE计划提供基础架构 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。阶段的具体目的 III CPVB COBRE是：i）在心肺血管生物学领域授予高影响力的研究项目； ii）在细胞隔离和离体器官功能（CIOF），线粒体中提供有效且高质量的服务 功能和体内成像（MF-II）； iii）与罗德岛（RI）和其他州的Idea计划合作 通过提供编程，资金，技术服务和资源来增强科学网络 研究生产力；和iv）维持血管生物学的强大调查线 科学界和进一步的预防和治疗心肺血管的研究 疾病。我们将通过促进新的合作来扩展和丰富血管生物学研究社区 并从各个学科中吸引新手的科学家。在第三阶段结束时，我们希望 过渡到可持续的CPVB中心，该中心是CVPB研究社区的住所 核心服务，大量的机构支持以及继续发展有效的承诺 战斗或解决心肺血管疾病的方法。 补充剂奖将解决的研究问题：右心（RV）功能障碍 肺动脉高压（pH）与不良的结局有关，而相关的合并症和 基本条件。 pH是常见的，折磨约占世界人口的1％，通常与 心肺疾病，在许多情况下与肺血管重塑有关。尽管有 迄今为止，与RV功能障碍相关的已知不良预后，尚无RV靶向疗法，并且 RV功能障碍的潜在机制尚不清楚。因此，没有满足的需求 了解与RV功能障碍相关的细胞和分子机制，并将其转换 了解疗法。与RV功能障碍相关的病理生理机制包括变化 心肌的细胞组成，基质重塑（例如纤维化），代谢功能障碍，导致心脏 衰竭，心室和心律不齐。而还原主义的方法导致了重要的见解 进入特定细胞类型和信号通路的作用，这是一种使用多尺度和多尺度和多尺度的全面评估 法学评估和使用新型数据科学分析技术，以识别网络和途径 尚未执行不良适应性RV和RV功能障碍，这是该提案的总体目标。 为什么需要团队科学努力？考虑多种病理生理机制，细胞类型和 与RV功能障碍相关的表型（心律不齐，能量和机械故障），需要带来 心肌生物学，线粒体生物学和心律失常生物学专家。此外，使用大量 无偏见的数据集以揭示新型网络和RV功能障碍潜在的途径需要分析和 减少数据维度和识别重要多OMIC网络的方法学专业知识 使用基于人工智能的新型方法的特征，与适应不良的表型有关 RV功能障碍的设置。这些数据，方法和协作有望导致多PI和 计划项目赠款应用程序将导致可持续团队进行有影响力的科学研究 在心肺血管疾病中，例如RV功能障碍和失败。