Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a median survival of 2-5 years. The incidence of IPF increases with age, thus IPF will affect more individuals as the population continues to grow older. There is no effective treatment for IPF except lung transplantation. Our current understanding of IPF suggests that pathogenesis begins when environmental factors alter normal lung homeostasis in a genetically or epigenetically susceptible individual. This altered state disrupts normal cell communication and induces a wound healing response, ultimately leading to irreversible fibrosis of the lung parenchyma. Although the exact etiology of IPF is unknown, pro-fibrotic macrophages have been implicated in disease pathogenesis. Preliminary data suggests that patients with IPF have a population of disease-specific macrophages. This proposal aims to elucidate the role of specific histone modifications on disease-specific macrophage transcriptome in IPF.
Aim 1 combines biochemical and genetic tools to identify the targets and regulators of histone modifications in IPF- specific macrophages.
Aim 2 will evaluate the transcriptional changes directly caused by presence or absence of a histone modification in macrophages. These experiments will elucidate a mechanism of macrophage dysfunction with direct translational implications for patients with IPF.
Macrophages are thought to drive excessive scar tissue in patients with idiopathic pulmonary fibrosis (IPF), a deadly lung disease with no cure other than lung transplantation. This proposal aims to understand the epigenetic profile of macrophages present in the lungs of patients with IPF but not found in healthy people or patients with another pulmonary disease. Completion of this work will assist in identifying new avenues of therapy for this devastating lung disease.
