Program on cellular metabolism and lung fibrosis

细胞代谢和肺纤维化项目

• 批准号: 10320790
• 负责人: Gang Liu
• 金额: $ 74.25万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-03 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320790
• 关键词: Affect; Cells; Chronic Obstructive Pulmonary Disease; Clinical; Diagnosis; Disease; Epigenetic Process; Foundations; Functional disorder; Genetic; Life Expectancy; Light; Lung; Lung diseases; Metabolic; Metabolic Pathway; Metabolism; MicroRNAs; Pathogenesis; Pharmacology; Phenotype; Program Description; Pulmonary Fibrosis; Pulmonary Hypertension; Refractory Disease; Research; Role; Solid; Translating; Vision; Work; base; cell type; design; effective therapy; idiopathic pulmonary fibrosis; improved; insight; intercellular communication; novel; novel therapeutic intervention; programs; promoter

Abstract Idiopathic pulmonary fibrosis (IPF) is a clinically refractory disease with a life expectancy of 2-6 years after diagnosis. Despite decades of extensive research, effective treatments for IPF are disappointingly limited. There is a pressing need for discovering novel therapeutic strategies based on better understanding of the disease pathogenesis. This program is based on my prior work and vision that lung fibrosis is characterized by perturbations of distinct core metabolic programs in different types of pulmonary cells, a potentially paradigm- shifting concept that has just begun to be appreciated. Delineation of how core metabolic pathways are specifically regulated, particularly at the epigenetic level by specific miRNAs, in different pulmonary cell types, how they contribute to the pro-fibrotic phenotypic alterations of the affected cells, and how metabolic intermediators act in intercellular communication to promoter pulmonary cell dysfunction will significantly advance our understanding of the pathogenesis of lung fibrosis. In this program, we will use genetic, epigenetic and pharmacological approaches to fine-tune dysregulated core metabolic program in the lung to gain novel insight into the contributions of core metabolic abnormalities to lung fibrosis pathogenesis and to determine the best strategies to fix these metabolic aberrations for treating this disease. I believe that my program will lay a solid foundation for designing potentially ground-braking metabolic approaches to effective lung fibrosis therapies. My program will also shed new light into disease mechanism of many other mechanistically related pulmonary disorders, such as pulmonary hypertension and COPD.

摘要