University of Virginia Health System

The formation of new microvessel networks is a critically important event in many normal and pathological adaptations. Proper network assembly involves formation of new capillaries then investment of these new capillaries with perivascular or smooth muscle cells. Our research seeks to understand how molecular signals and hemodynamic stresses coordinate the assembly of these networks. Specifically, the laboratory is studying how migrating vascular cells are guided by underlying matrix protein scaffolds and how the process of capillary investment with perivascular cells is controlled by signaling molecules produced by capillary wall cells in response to alterations in blood pressure and flow. The delivery of genes and drugs encased in liposomes to specific regions of the body is often hindered by the endothelial lining of microvessels. We have observed that under certain conditions, insonified albumin-shelled microbubbles can produce ruptures in small skeletal muscle microvessels, allowing intravascular gene- and drug-bearing liposomes to pass across the endothelial lining in ultrasonically targeted regions in the body. Studies are currently aimed at determining optimal ultrasound parameters and microbubble composition for producing various rupture sizes in tissue and testing this technique for its ability to enhance the delivery of gene- and drug-bearing liposomes to tumors and myocardium.