William Muller, MD, PhD
Professor, Pathology; Feinberg School of Medicine
Research Program
Cancer-Focused Research
My 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 recently described the Lateral Border Recycling Compartment (LBRC), a novel para-junctional organelle that contains PECAM and CD99 and is critical for diapedesis to occur. During diapedesis, membrane from this compartment traffics rapidly along microtubules to surround the leukocyte, providing a source of critical adhesion/signaling moleucules and expanding the membrane surface area of the junction. This trafficking is critical for transendothelial migration of neutrophils, monocytes, and lymphocytes and appears to be the final common pathway for transmigration. Not only do leukocytes use the LBRC for transmigration, but we have preliminary data that cancer cells may usurp this pathway to exit the vasculature during metastasis. We are interested in pursuing these studies using in vitro and in vivo models of cancer cell extravasation.