Idiopathic Pulmonary Fibrosis (IPF) is characterized by progressive pulmonary scarring and decline in lung function. Lung epithelial injury and aberrant recovery is believed to be central to the pathogenesis of IPF. The median survival for IPF is 3-5 years after diagnosis, the underlying cause of IPF is not known, and pharmacologic treatments have limited efficacy. Fibroblast Growth Factors (FGFs) are implicated in the pathogenesis of IPF, although the mechanism through which FGFs promote fibrogenesis is unclear. We study cellular mechanisms of FGF and growth factor signaling in pulmonary fibrosis, using transgenic mouse models of lung injury and pulmonary fibrosis. Projects in the lab focus on cell-specific growth factor signaling and their role in 1) recovery from lung injury and 2) fibroblast activation and pulmonary fibrosis.

Examples of projects include: 1) Study the requirement of FGF2 for epithelial recovery following injury. This project involves assessment of lung epithelial proliferation and differentiation in FGF2 wild-type and knockout mice using lineage tracing analysis. To determine if FGF2 is protective in response to injury, mice with inducible overexpression of FGF2 will be used.

2) Determine the requirement of epithelial FGF receptor signaling in the development of pulmonary fibrosis. This project involves the use of mice with lung epithelial-specific FGF receptor knockouts, and will evaluate development of pulmonary fibrosis in response to bleomycin treatment.

3) Determine fibroblast-specific signaling involved in pulmonary fibrosis. This project will involve gene expression and protein analysis of fibroblasts from IPF patients and mice treated with bleomycin. The mice in this project are engineered to have fibroblast-specific FGF receptor knockouts, fibroblasts from WT or knockout mice are collected using cell sorting, and quantitative RT-PCR or western blot analysis is performed using both cultured and freshly sorted cells.

Techniques required will depend upon the project performed. Techniques used in the laboratory include the following: Histology, Immunohistochemistry, Immunofluorescence, western blot, quantitative RT-PCR, Flow cytometry, cell sorting, primary cultures of mouse lung epithelium and fibroblasts, mouse intubation and administration of intratracheal bleomycin.

Graphpad (Graphpad and any other required software will be provided)

Pulmonary Research In Progress Seminar, Weekly lab meeting