University of Virginia Health System

Our laboratory is developing applications of molecular mechanics to the challenges of targeted drug and gene delivery. To increase specificity and reduce toxic side effects, we are incorporating leukocyte adhesion receptors into liposomes and polymeric microparticles containing encapsulated therapeutics to target defective cells with high specificity. To this end, we are using a mutagenesis approach coupled with biophysical analysis of mechanically stressed bonds to identify the controlling features of adhesion receptors that permit binding in the presence of fluid shear forces. Additionally, we have developed several model flow systems to examine the dynamics of platelet-leukocyte-vessel wall interactions that take place during the acute phases of an inflammatory challenge or the formation of blood clots on the vessel wall. Common to interactions between platelets, leukocytes, and the vessel wall is the involvement of a family of receptors called selectins that support transient adhesions in which leukocytes and platelets roll along the vessel wall in shear flow. These studies have significance for the understanding of the regulatory effects of blood flow, adhesion receptor expression, and chemokines on inflammatory responses and blood clotting.

• NIH Style Biographical Sketch
• Current Techniques and Protocols (UVA Intranet log-in required)