Mechanobiology of Cardiopulmonary Fibrosis

心肺纤维化的力学生物学

• 批准号: 10535459
• 负责人: WILLIAM D MERRYMAN
• 金额: $ 76.41万
• 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/10535459
• 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; Translating; cost; innovation; novel; prevent; programs; pulmonary arterial hypertension; right ventricular failure; treatment strategy

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.

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