Nathan Sandbo, M.D.

Dalsemer Research Grant: Targeting Cell Signaling Process May Stop Scarring in Pulmonary Fibrosis

Nathan Sandbo, M.D., would one day like to be able to tell his patients with idiopathic pulmonary fibrosis (IPF) that there is an effective treatment for them. "Now, when I have to give a patient a diagnosis of pulmonary fibrosis, it is challenging and disconcerting, because there are no effective therapies," he says.

His patients are his motivation for trying to understand the process by which cells in the lung called fibroblasts become overactive and change shape, leading to fibrosis, or scarring, in the lungs. With an American Lung Association Dalsemer Research Grant, Dr. Sandbo is studying fibroblasts, and hopes that his research could lead to treatments for IPF. Dr. Sandbo is focusing on how molecular "switches" inside fibroblasts get turned on by signals outside of the cell and lead the fibroblasts to become overactive. One such signal is induced by a substance called Transforming Growth Factor-beta, or TGF-beta. "There is a first wave of TGF-beta signals that goes through the cell, which is well understood," he says. "But then there is a second signal wave that is less well understood, which may be a new target for therapies for pulmonary fibrosis." Dr. Sandbo is investigating how this second wave of signaling leads to the production of proteins that change the shape and structure of the fibroblast cells and leads to lung scarring.

There are already some therapies in development that target TGF-beta. But Dr. Sandbo says that because it is a molecule that is involved in normal cell processes as well as disease, using a drug that broadly targets TGF-beta could interfere with normal cell functioning and lead to unintended problems. "If we can identify the molecules and mechanisms involved in this later wave of cell signaling involving TGF-beta, we would have a more specific target for drugs that stop the fibrosis process but don’t interfere with normal tissue functioning," he says. Dr. Sandbo says he is grateful for the American Lung Association grant, which has allowed him to hire a technician and purchase supplies to move his research forward. "I’m a young investigator just starting out in my career, and this support is immensely helpful," he says.