About

Most diseases are due to or involve a significant component of inflammation. The Muller Lab studies the inflammatory response at the cellular and molecular level. We are focused on the process of diapedesis, the “point of no return” in inflammation where leukocytes squeeze between tightly apposed endothelial cells to enter the site of inflammation. We have identified and cloned several molecules that are critical to the process of diapedesis (PECAM (CD31), CD99, and VE-cadherin) and are studying how they regulate the inflammatory response using in vitro and in vivo models. We have described the Lateral Border Recycling Compartment (LBRC), a novel para-junctional organelle that contains PECAM and CD99 and is critical for diapedesis to occur, seemingly independent of the leukocyte type, inflammatory stimulus, or vascular bed. We are currently investigating how this compartment regulates diapedesis in the hope of finding novel targets for anti-inflammatory therapy. Our discovery that a single splice form of a single kinesin light chain is required for moving the LBRC to the site of diapedesis has led to the design of a prototype anti-inflammatory drug that is currently being tested in several mouse models. Our inflammatory models include atherosclerosis, myocardial infarction, ischemia/reperfusion injury, stroke, dermatitis, multiple sclerosis, peritonitis, acute and chronic lung diseases, and rheumatoid arthritis. We are also using 4-dimensional intravital microscopy to view the inflammatory response in real time in living animals. In addition to performing intravital microscopy in standard vascular beds such as cremaster muscle, skin, and mesentery, we are in the process of expanding our capabilities to include the vascular beds of the lung, cerebral cortex, and retina.