Sarah Childs

We are interested in angiogenesis, the process by which new blood vessels develop. Blood vessels first develop as naked endothelial tubes, and then acquire a coating of ‘mural’ cells (either smooth muscle cells or pericytes). Dysfunctional vessels underlie a large number of serious diseases. We focus on using developmental biology to tease out the signals that grow and stabilize new blood vessels as a means to potential therapy for blood vessel disorders. Project in vascular patterning:Blood vessels are customized for delivery of oxygen and nutrients to different organs with different architectures and metabolic needs. How do blood vessels acquire organ-specific patterns? In this project we examine the normal patterning of blood vessels during development and the molecular pathways that control their pattern. We also examine the role of patterning genes such as the PlexinD1 receptor to determine how it guides vascular development using genetic analysis of ligands and signalling pathways. We have a strong interest in GTPase control of the actin cytoskeleton in vascular development, and their particular roles in diseases such as vascular malformation. Project in vascular stabilization:The origins of mural cells are not well understood. In the head, mural cells are thought to originate in neural crest cells, but how do they migrate to specific vessels and what signals allow them to contact and ensheath endothelial cells? In this project we examine the genetic control of mural cell development. Using transgenic smooth muscle and pericyte marker lines we trace mural cell migration in real time. Loss of mural cell attachment to endothelial cells results in brain hemorrhage. We have developed mutant animals with defective vascular stabilization that are models of both hemorrhagic and ischemic stroke.