Mechanobiology of Cardiopulmonary Fibrosis

总结 心肌纤维化是多种病理的统一因素，包括心肌后纤维化。 心肌梗死（MI）瘢痕形成，导致心力衰竭、心脏瓣膜病（HVD）和肺动脉高压。 动脉高血压（PAH）等。我的实验室探索成纤维细胞驱动的， 心肺纤维化重塑的机械生物学机制，并开发创新 预防或治疗这些疾病的方法。我们专注于心肺成纤维细胞， 它们独特的表型特征可被靶向以阻止它们的纤维化机制。我们独一无二 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的承诺提供了强有力的证据， 我们理解的差距，导致新的治疗策略的发展。最初我们 专注于HVD，但后来扩展到一般心肺纤维化，包括PAH， 导致右心衰竭和心肌梗死后的纤维化。这些新的追求是 补充我们在HVD完善的研究计划，并结合我的实验室的 NHLBI的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：1）在过去的成就的基础上，同时保持目前的努力， 足够灵活地追求研究活动过程中出现的机会; 2）巩固 心肺机械生物学的价值，并定位我的团队，不仅继续我们的 研究，但“种子”的专业知识更广泛地在NHLBI社区; 3）最大限度地共同 更有效地使用昂贵的试剂和动物模型; 4）支持我的八人小组 稳定状态的实习生，包括两名初级教师。

Summary 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.