DEPARTMENT OF MOLECULAR PHYSIOLOGY
AND BIOLOGICAL PHYSICS
Research Opportunities
Dr. Brian R. Duling
Cell-cell Signaling in the Microcirculation and Selective Genetic Manipulation of Connexin Expression
Much of cardiovascular pathophysiology derives ultimately from deranged function of either the smooth muscle or the endothelium of the microvessels. Our laboratory focuses on the means by which the cells of the arteriolar wall operate as a coordinated unit. Using video microscopy of living cells in situ, we operate at the interface between cell and integrative biology. State-of-the-art imaging technologies and computer processing, combined with newly developed cell-specific surface labels and detection indicators allow us to visualize the individual cells of the microvessel wall, as well as the formed elements of the blood in the living animal. Using these tools, we have three major experimental efforts underway.
First, we are attempting to understand the role played by the endothelial cell glycocalyx in the control of erythrocyte and leukocyte distribution in the mircrovessels. This work has special relevance to the factors which regulate tissue oxygen supply, and the permeability of the microvessels to solutes and water. Second, we are studying the chemical, mechanical, and electrical signaling processes, which establish cell-cell communications within and between smooth muscle and endothelial cell. Our special interest is in the role of gap junctions in the vessel wall. This work is facilitated by the use of cell specific regulation of gene knockout in smooth muscle and endothelial cells. Third, we are searching for the trigger mechanisms responsible for stretch and flow sensitivity of blood vessels. These three experimental programs are part of an ongoing effort to understand the vasculature as a communications network, and to discover how the functions of the vasculature are matched to the needs of the organ and organism.