Grant: Operating Grant

When bacteria or viruses enter the bloodstream, the body has to recognize these foreign infectious agents and then respond to contain these agents. Infectious agents are recognized by a family of proteins on the cell surface called Toll-like receptors (TLR). When TLRs recognize the presence of an infection they send a signal to the inside of the cell called an innate immune signal. However, these same receptors also respond to various proteins that are normally present in the body. It is thought that blood vessels play a crucial role in development of many organs in the fetus. This proposal is designed to understand how the cells lining the inside of blood vessels, called endothelial cells regulate the development of the lung. We are interested in the innate immune signals within the endothelial cell that regulate how the lung develops. We have discovered a new gene that we believe plays a role in regulating the signal transmitted by specific TLRs on endothelial cells. When this gene is deleted in mice, the newborn animals are unable to breathe. Our early experiments suggest that this is because they are not able to inflate their lungs. The studies in this grant are designed to understand how Sash1 functions to send signals within the endothelial cell and how these signals then affect the normal development and function of lung cells in the fetus.