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.

Public Health Relevance

Description The program is built around my vision that pulmonary metabolic dysregulation has an important role in the pathogenesis of lung fibrosis. The studies proposed in this program should not only improve understanding of the participation of metabolic abnormalities of different types of pulmonary cells in progression of lung fibrosis, but also are likely to provide solid groundwork for translating metabolic approaches into effective lung fibrosis therapies.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Unknown (R35)
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Special Emphasis Panel (ZHL1)
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Craig, Matt
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University of Alabama Birmingham
Internal Medicine/Medicine
Schools of Medicine
United States
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Lutful Kabir, Farruk; Ambalavanan, Namasivayam; Liu, Gang et al. (2018) MicroRNA-145 Antagonism Reverses TGF-? Inhibition of F508del CFTR Correction in Airway Epithelia. Am J Respir Crit Care Med 197:632-643
Liu, Gang; Summer, Ross (2018) Cellular Metabolism in Lung Health and Disease. Annu Rev Physiol :
Cui, Huachun; Xie, Na; Banerjee, Sami et al. (2018) Impairment of Fatty Acid Oxidation in Alveolar Epithelial Cells Mediates Acute Lung Injury. Am J Respir Cell Mol Biol :
Ge, Jing; Cui, Huachun; Xie, Na et al. (2018) Glutaminolysis Promotes Collagen Translation and Stability via ?-Ketoglutarate-mediated mTOR Activation and Proline Hydroxylation. Am J Respir Cell Mol Biol 58:378-390
Cui, Huachun; Banerjee, Sami; Guo, Sijia et al. (2018) IFN Regulatory Factor 2 Inhibits Expression of Glycolytic Genes and Lipopolysaccharide-Induced Proinflammatory Responses in Macrophages. J Immunol 200:3218-3230
Liu, Gang; Thannickal, Victor J (2017) The Lung Likes the Little Fella miR-29. Am J Respir Cell Mol Biol 57:637-638
Jiang, Chunsun; Liu, Gang; Luckhardt, Tracy et al. (2017) Serpine 1 induces alveolar type II cell senescence through activating p53-p21-Rb pathway in fibrotic lung disease. Aging Cell 16:1114-1124
Cui, Huachun; Ge, Jing; Xie, Na et al. (2017) miR-34a promotes fibrosis in aged lungs by inducing alveolarepithelial dysfunctions. Am J Physiol Lung Cell Mol Physiol 312:L415-L424
Cui, Huachun; Ge, Jing; Xie, Na et al. (2017) miR-34a Inhibits Lung Fibrosis by Inducing Lung Fibroblast Senescence. Am J Respir Cell Mol Biol 56:168-178
Xie, Na; Cui, Huachun; Ge, Jing et al. (2017) Metabolic characterization and RNA profiling reveal glycolytic dependence of profibrotic phenotype of alveolar macrophages in lung fibrosis. Am J Physiol Lung Cell Mol Physiol 313:L834-L844