Leukocyte Diapedesis
Our investigations of the cell biological basis of immune cell trafficking have generated a range of insights. Dynamic, high-resolution imaging revealed that endothelium form actin-based structures termed ‘transmigratory cups’ that embrace’ the immune cells and help guide their egress into the tissue. We also, showed for the first time in vitro that leukocytes can cross the endothelium not only by squeezing between endothelial cells but also by penetrating individual endothelial cells directly (i.e., ‘trans-cellularly’). We further uncovered new actin-rich protrusion ‘Invadosome-like protrusions’ (ILPs) that facilitate leukocyte pathfinding and barrier breaching.
Our current studies endeavor to understand biomechanical sensing by leukocytes that facilitates these critical capabilities. We have also developed analogous studies to investigation how mesechymal stem cells (an emerging anti-inflammatory therapeutic) traffick across the endothelium through both in vitro and intravital imaging approaches.