Her project, titled “TRPC4-Dependent Cytosolic Calcium Signals Coordinate Interendothelial Forces That Elicit Gap Formation,” studies the mechanism underlying inflammation-induced lung tissue swelling.
According to Dr. Xu, her research has far-reaching potential to impact patient care, as lung tissue swelling contributes significantly to the mortality and morbidity of patients in intensive care units. “Lung endothelial cells, which form a barrier to keep blood contents within the vessels, express pore-forming proteins in their plasma membranes to form calcium channels known as the canonical transient receptor potential 4, or TRCP4,” she said. “Inflammatory substances in the bloodstream cause the TRPC4 channel to open and allow calcium ions to enter the lung endothelial cells. Calcium influx serves as a critical signal to pull endothelial cells apart and form holes in the vessel wall. Thus, fluid, proteins and blood cells in the bloodstream penetrate through these holes into the interstitium, leading to lung tissue swelling.”
Dr. Xu said the ultimate goal is to perform a target-based drug screen and identify new drugs targets for lung swelling patients. “This grant allows me to test my hypothesis and pave the way to discover novel and effective drugs for lung edema patients,” she said. “Reducing contractile forces and improving lung endothelial barrier integrity could be potential drug targets to reduce lung endothelial permeability.”
“I would like to thank the many people who helped me during this grant application,” said Dr. Xu. “My mentor and sponsor, Dr. Troy Stevens, along with my co-sponsor Dr. Dhananjay Tambe, guided me through this proposal.”
Dr. Xu also credits a host of supporters, secretaries and grant officers for playing a vital role in helping her secure the three-year grant from the NIH: Drs. Elly Trepman (Grand Rapids, Minn.), Mary Townsley, Mikhail Alexeyev, Silas leavesley, Mike Lin, Michael Francis, Thomas Rich, Mark Taylor, Donna Cioffi, Michelle Schuller, Diego Alveraze, Steve Lim, and Ms. Charlene Jorden, Kelli Robinson, Penny Cook, and Jennifer Collins. “Thank you all for the support to make this happen,” Dr. Xu said.
The Ruth L. Kirschstein-NRSA postdoctoral fellowship is designed to enhance the research training of promising postdoctoral candidates who have the potential to become productive, independent investigators in scientific health-related research fields relevant to the missions of the participating NIH Institutes and Centers. Learn more about the grant here.
