CardioPulmonary Vascular Biology COBRE

心肺血管生物学科博尔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 开发有效的方法预防和治疗影响肺和心血管的血管疾病 通过更好地了解疾病的机制，提高对疾病系统的认识。这是通过充当一个 跨学科中心，促进合作研究，提供出色的技术支持和 将资源分配给调查人员。CPVB Cobre项目的总体使命一直是建立人类和 作为国家增加CPVB研究的催化剂的技术基础设施和服务。 心血管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，有必要了解心肺血管疾病的发病机制。 以开发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 拥有行政、试点项目和两个技术核心，从而提供了扩大以下领域的机会 调查、实验和技术方法以及科学合作。阶段性的具体目标 CPVB Cobre将：i)授予在心肺血管生物学领域具有重大影响的研究项目； 二)在细胞分离和体外器官功能(CIOF)、线粒体方面提供有效和高质量的服务 功能和活体成像(MF-II)；iii)与罗德岛(RI)和其他州的IDEA计划合作，以 通过提供规划、资金、技术服务和资源促进科学网络 研究生产力；以及iv)保持强大的血管生物学研究队伍，以满足以下需求 心肺血管疾病防治的科学界与深入研究 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社区 以及吸引来自不同学科的新科学家。在第三阶段结束时，我们预计 向可持续发展的CPVB中心过渡，作为CVPB研究社区的高质量家园 核心服务，重要的机构支持，并承诺继续发展有效的 防治或解决心肺血管疾病的方法。 补充奖将解决的研究问题：右室功能障碍 肺动脉高压(PH)与不良预后有关，而不考虑相关的合并症和 潜在的条件。PH是一种常见的疾病，困扰着世界约1%的人口，通常与 心肺疾病，在许多情况下与肺血管重塑有关。尽管 已知的与RV功能障碍相关的不良预后，到目前为止，还没有RV靶向治疗可用，并且 RV功能障碍的潜在机制尚不清楚。因此，有一种对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RV功能障碍相关的病理生理机制包括 心肌细胞组成、基质重构(如纤维化)、导致心脏的代谢功能障碍 心衰以及室性和房性心律失常。虽然简化论者的方法带来了重要的见解 对于特定的细胞类型和信号通路的作用，采用多尺度和多层次的综合评价方法 组学评估和使用新的数据科学分析技术来确定 潜在的适应性不良的RV和RV功能障碍还没有进行，这是本提案的总体目标。 为什么需要团队科学的努力？考虑到多种病理生理机制，细胞类型和 与RV功能障碍相关的表型(心律失常、能量和机械衰竭)，需要 汇集了心肌生物学、线粒体生物学和心律失常生物学的专家。此外，使用大型 要解开RV功能障碍背后的新网络和通路，需要无偏数据集的分析和 在数据降维和重要多组学网络识别方面的方法专长 使用新的基于人工智能的方法的功能，这些功能与 右室功能障碍的设置。这些数据、方法和协作预计将导致多PI和 计划项目拨款申请，将导致可持续的团队进行有影响力的科学研究 在心肺血管疾病中，如右室功能障碍和衰竭。

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.