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.