Andrew Haak, Ph.D.
Funded by the American Lung Association of the Upper Midwest
Seeking Therapeutic Targets for Idiopathic Pulmonary Fibrosis
Interstitial pulmonary fibrosis (IPF), which causes scarring of the lungs, has limited treatment options. Cells called myofibroblasts are a core contributor to lung scarring, or fibrosis. Recent studies have identified an important role for two proteins called transcription factors in activating these myofibroblasts. Stimulating a specific class of cell receptors can block these transcription factors. We will study whether activating these receptors in lung myofibroblasts will reduce these cells scarring effect in IPF. This class of receptors is one of the most common targets for clinically approved drugs. Many of the compounds we are testing are approved drugs with a long history of safe, effective use. We are hopeful that we can identify one or more treatments for IPF from these compounds.
Update: The main goal of the first year of this project was to identify a compound that can selectively inhibit YAP and TAZ transcription factors in lung fibroblasts while not affecting epithelial and endothelial cells, which line the insides of blood vessels. We have since validated that our original lead compound affects only lung fibroblasts, and is effective in test-tube models of lung fibrosis. Our plan for the second year of this project is to run a full scale mouse model experiment and expand our compound search to identify the best molecule to continue these studies in the future.