Dr. Ulrich von Andrian

Harvard Medical School, USA

Research in the von Andrian lab seeks answers to the question how circulating blood cells find their way in the body.

Directed migration of blood-borne cells to distinct target tissues can be observed in embryos as soon as the circulatory system is established and plays a critical role throughout life in numerous physiologic and pathologic conditions. Despite considerable progress in this field, it is still beyond the reach of even the most sophisticated in vitro methodology to simulate the complex interplay of physical, cellular, biochemical, and other factors that determine blood cell behavior in micro-vessels. Therefore, the von Andrian lab employs intravital microscopy to study the molecular mechanisms of interactions between blood cells and the vascular wall by direct observation in anesthetized mice. Using this approach, they have demonstrated that blood cell homing to most target tissues requires an initial tethering step that leads to rolling in postcapillary venules and is followed by an activation step which, in turn, triggers stationary adhesion and emigration. Each of these three steps (i.e. 1. rolling; 2. chemotactic stimulation; and 3. firm arrest) involves distinct molecular pathways whose unique combination is the reason why certain blood cells migrate to a particular organ, whereas others don’t.

von Andrian and colleagues are now dissecting the site-specific adhesion cascades that direct leukocytes, hematopoietic stem cells, and platelets to normal and diseased tissues. They have established models in mice that allow quantitative observations in the gut; bladder; striated muscle; skin; pancreas; liver; bone marrow; bone; and peripheral lymph nodes. The techniques for observing the latter three tissues were developed in the von Andrian lab.

Understanding how lymphocytes, in particular T cells, home to and migrate within peripheral lymph nodes is a major focus of the von Andrian group. To this end, they are using a panel of mice that are genetically deficient in specific adhesion pathways. They have also generated transgenic mouse strains that express fluorescent proteins in distinct T cell subsets; they are using these mice to study how T cells differentiate into effector and memory subsets; how this differentiation affects their migratory properties; and how antigen-presenting dendritic cells influence these processes. T cells and dendritic cells can be visualized in the intra- and extravascular space by intravital microscopy using both single- and multi-photon fluorescence techniques. This allows von Andrian and colleagues to dissect the trafficking behavior of these immune cells at a resolution and specificity that could not otherwise be achieved.

Von Andrian received his M.D. and Ph.D. from Ludwig-Maximilians University in Munich, Germany. He did postdoctoral work at the La Jolla Institute for Experimental Medicine in California. He is a member of the European Academy of Sciences and the American Society for Cell Biology, and in 2004 he was awarded the Amgen Outstanding Investigator Award.