Mechanobiology of Cardiopulmonary Fibrosis

心肺纤维化的力学生物学

• 批准号: 10397848
• 负责人: WILLIAM D MERRYMAN
• 金额: $ 3.72万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-11 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10397848
• 关键词: Address; Animal Disease Models; Animal Model; Cardiopulmonary; Cells; Cicatrix; Communities; Development; Disease; Engineering; Faculty; Fibroblasts; Fibrosis; Future; Heart Valve Diseases; Heart failure; In Vitro; Laboratories; Myocardial Infarction; National Heart, Lung, and Blood Institute; Pathology; Patients; Phenotype; Positioning Attribute; Reagent; Research; Research Activity; Seeds; Translating; cost; innovation; novel; prevent; programs; pulmonary arterial hypertension; treatment strategy

PROJECT SUMMARY/ABSTRACT Cardiopulmonary fibrosis is a unifying factor in multiple pathologies, including post myocardial infarction (MI) scarring that leads to heart failure, heart valve disease (HVD), and pulmonary arterial hypertension (PAH), among others. My laboratory explores fibroblast-driven, mechanobiological mechanisms of cardiopulmonary fibrotic remodeling and develops innovative strategies to prevent or treat these diseases. We focus on cardiopulmonary fibroblasts and how their unique phenotypic signatures can be targeted to halt their fibrotic machinery. We uniquely leverage our engineering expertise to address mechanobiological inputs that drive cardiopulmonary fibrosis, by effectively combining animal models of disease with primary cell in vitro studies. Our prior accomplishments provide strong evidence for future promise to bridge key gaps in our understanding that leads to development of novel treatment strategies. Initially, we focused on HVD, but have since expanded into general cardiopulmonary fibrosis, including PAH, which results in right heart failure, and fibrosis following MI. These new pursuits are complementary to our well-established research program in HVD and combining my laboratory’s NHLBI research portfolio would allow us to make rapid progress and translate our findings to patients by: 1) building on past accomplishments, while sustaining present efforts and being nimble enough to pursue opportunities presented in the course of research activities; 2) solidifying the value of cardiopulmonary mechanobiology and positioning my group to not only continue our research but to “seed” expertise more broadly in the NHLBI community; 3) maximizing common use of costly reagents and animal models more effectively; 4) supporting my group of eight trainees at steady state, including two junior faculty.

项目总结/摘要 心肌纤维化是多种病理的统一因素，包括心肌梗死后（MI） 导致心力衰竭、心脏瓣膜病（HVD）和肺动脉高压（PAH）的瘢痕形成， 还有其他的我的实验室探索了成纤维细胞驱动的心肺功能的机械生物学机制。 纤维化重塑和开发创新的策略，以预防或治疗这些疾病。我们专注于 心肺成纤维细胞以及如何靶向它们独特的表型特征以阻止它们的纤维化 机械.我们独特地利用我们的工程专业知识来解决机械生物学输入， 心肺纤维化，通过有效地结合疾病的动物模型与原代细胞体外研究。 我们先前的成就为未来弥合我们认识上的关键差距提供了强有力的证据 这导致了新的治疗策略的发展。最初，我们专注于HVD，但后来扩大了 一般心肺纤维化，包括PAH，导致右心衰竭，以及 MI.这些新的追求是我们在HVD完善的研究计划的补充，并结合我的 实验室的NHLBI研究组合将使我们能够取得快速进展，并将我们的发现转化为患者 通过：1）以过去的成就为基础，同时保持目前的努力，并灵活地追求 研究活动过程中提供的机会; 2）巩固心肺功能的价值 机械生物学和定位我的小组不仅继续我们的研究，但“种子”的专业知识更广泛 在NHLBI社区; 3）更有效地最大限度地提高昂贵试剂和动物模型的通用性; 4） 支持我在稳定状态的八名学员，包括两名初级教师。