Mechanobiology of Cardiopulmonary Fibrosis

项目摘要/摘要 心肺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)的疤痕形成， 还有其他的。我的实验室探索成纤维细胞驱动的心肺机械生物学机制 纤维化重塑，并开发创新的策略来预防或治疗这些疾病。我们专注于 心肺成纤维细胞及其独特的表型特征如何被靶向阻止其纤维化 机械设备。我们独一无二地利用我们的工程专业知识来解决驱动 心肺纤维化，通过有效地结合疾病的动物模型和体外原代细胞研究。 我们以前的成就为未来弥合我们理解中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，但后来扩展了 转化为全身性心肺纤维化，包括导致右心衰竭的PAH，以及随后的纤维化 密西西比。这些新的追求是对我们在HVD的成熟研究计划的补充，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)在过去成就的基础上，保持目前的努力并足够灵活地追求 在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团队不仅要继续我们的研究，而且要在更广泛的范围内“播种”专业知识 在NHLBI社区；3)更有效地最大限度地使用昂贵的试剂和动物模型；4) 在稳定状态下支持我的八名实习生，其中包括两名初级教员。

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.