We study both acute and chronic inflammation and in particular the mechanisms of leukocyte recruitment within the vasculature in vivo using intravital microscopy and in vitro using endothelial monolayers and flow chambers.
We have contributed significantly to the current leukocyte recruitment paradigm that consists of tethering, rolling, firm adhesion and transmigration. Importantly we have demonstrated the importance of unique tissue specific recruitment cascades in organs such as liver. As well we have uncovered novel roles of known adhesion molecules in leukocyte behaviors such as intravascular crawling.
We are interested in defining the host immune response to multiple different pathogens during intravascular and parenchymal infections. A major focus has been to investigate novel neutrophil mediated strategies of host-defense against antibiotic resistant Staphylococci aureus. We have defined a novel means by which neutrophils in vitro and in vivo release DNA in large mesh structures (neutrophil extracellular traps, NETs) in order to trap bacteria at focal sites like skin.
Intravascular pathogens pose significant problems for innate immune cells as no focus of infection exists to direct leukocyte recruitment. We are interested in how the liver, a highly vascular organ, mediates effective host defense via specialized cells named Kupffer and NKT cells.
Tissue and cellular injury occurs following many different pathological insults, including trauma, ischemia reperfusion, and necrosis. We are interested in how non-infectious sterile injury results in inflammation and how these mechanisms differ from infectious stimuli. Our lab has developed multiple sterile injury models using the liver and the brain that allow us to visualize the host response in real time. Using a liver model of sterile injury we have begun to define a novel hierarchy of danger signals required to recruit immune cells to the injured site.
We have also uncovered a surprisingly new link between sterile ischemic injury and immunity that begins to explain immunosuppression following brain injury due to acute stroke.
The Kubes lab is interested in studying immune mechanisms that are relevant to human disease. Some of the illnesses we are interested in are sepsis, cellulitis, hepatitis, stroke and Lyme disease.
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