Kel Woo, MD, PhD

High blood pressure in the lung, called pulmonary hypertension (PH), is a debilitating disease that affects premature babies and patients with lung disease. This research focuses on a specific type of PH caused by low oxygen. We developed a system to reproduce PH in mice by exposing them to low oxygen. We have identified signaling molecules called fibroblast growth factors (FGFs), and their receptors (FGFRs), that regulate PH. To learn how these molecules function, we engineered mice that activate FGFRs in cells that line blood vessels. When these mice are exposed to low oxygen levels, they do not develop PH. These preliminary studies suggest that FGFRs may function to prevent PH and that activating FGFRs might reduce disease severity. We proposed to (1) determine how activating FGFRs in mice prevents low oxygen-induced PH, and (2) investigate a new method of delivering the protective FGFR gene to the lungs and its ability to prevent PH. In our first year, we developed a system using human cells that line the blood vessels and turned them into muscle cells that would normally surround blood vessels. We also uncovered the proteins that are involved in this process as we had hypothesized in the proposal. We are now able to use this process to investigate the gene changes when cells are exposed to low oxygen environments. We also developed the tools for a new method of delivering the FGFR gene to lungs. We are now able to induce production of the protective FGFR gene in cells and are now ready to investigate their effect of preventing low oxygen-induced PH in our mouse models.

Update: We developed a system to test how human cells that line the blood vessels respond to low levels of oxygen. We found that low oxygen caused these lining cells to turn into muscle cells that would normally surround blood vessels. We also identified some of the signaling molecules that are involved in this process. We are now able to use this system to investigate the genetic changes that occur when cells are exposed to low oxygen environments. We also developed the tools for a new method of delivering gene to lungs that could prevent the detrimental response to low oxygen that causes pulmonary hypertension.