Edy Kim, MD, PhD

Idiopathic pulmonary fibrosis (IPF) is the most common type of lung fibrosis—a type of scarring of the lungs. IPF can cause progressive shortness of breath and death. We need new treatments for IPF, since the median survival is only 5 years. We will study a possible new approach to therapy: targeting a molecule called the LIF receptor (LIFR), which activates cells called fibroblasts that are a key part of the lung scarring. Several clinical trials in IPF that target one fibroblast activator at a time have failed. We propose that, by shutting down LIFR on fibroblasts, we can block the effects of many stimulators of scarring at the same time. We will first study how LIFR activates fibroblasts to cause scarring. Then we will show the feasibility of   a new treatment by silencing the LIFR gene in fibroblasts to improve lung fibrosis in a mouse model of IPF. This research will provide the foundation for developing a new treatment for lung fibrosis.

Innovation Award, applied under the Hastings Award

Update: This research is testing a new way to treat lung fibrosis, a disease in which scar tissue builds up in the lungs. Lung fibrosis can cause shortness of breath, low oxygen levels and death. Our team focuses on fibroblasts, the cells responsible for producing scar tissue in the lung. We discovered a “master switch” that controls the disease-causing activity of fibroblasts, the leukemia inhibitory factor receptor (LIFR). LIFR amplifies the response of fibroblasts to inflammatory and other disease-causing signals. In lab experiments, we found that turning off LIFR in fibroblasts from people with lung fibrosis reduced inflammation and scarring. Even better, turning off LIFR did not affect fibroblasts from healthy lungs, an important feature if we are designing new medications to turn off LIFR. We treated mice with a new type of therapy, tiny lipid nanoparticles to turn off LIFR in fibroblasts. This anti-LIFR medication reduced lung and skin fibrosis when given early in the disease. Our findings provide strong, early evidence that targeting LIFR could become the first “precision medication” to directly target the fibroblasts that drive lung fibrosis while preserving healthy lung function.