Dynamic response of neutrophils to chemokine stimulus
In the vasculature, inflammation leads not only to the expression of new adhesive ligands on the endothelial cell surface, but also the expression of signaling molecules (chemokines) that attract and activate leukocytes. An important chemokine that acts on neutrophils is IL-8, which is typically found immobilized on sugar structures (the gylcocalyx) on the endothelium. In order to imitate the natural presentation of chemokines to neutrophils, we immobilize IL-8 on a fractalkine stalk on the surface of a bead. By this approach, we can control the timing of the exposure of the cells to stimulus very precisely. We have completed several projects in this area, and continue to pursue others.
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Dynamics of bond formation between cells and substrates
A significant advantage of single cell micromanipulation is the ability to control the timing and duration of contact between cells and other surfaces, and also to control the chemistry of the surfaces with which the cell interacts. We have taken advantage of this capability, first to characterize the rate at which bonds form between a cell and a surface presenting a specific adhesion molecule, and second, to examine the dynamics of the cell response when it encounters specific stimulatory molecules immobilized on a surface.
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Mechanical force and leukocyte adhesion
When a tissue becomes injured or infected, the endothelial cells that line the blood vessels receive distress signals from the tissue that cause them to increase their expression of adhesion molecules and signaling molecules on their surface. Complementary molecules on white blood cells circulating in the blood (in our case, neutrophils) bind to these endothelial cell ligands, causing the neutrophils to roll along the vessel wall, stop, and then crawl through the endothelium into the tissue to fight the infection.
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Nano-structured bioreactors for blood cell production
Red blood cells are critical for life, and hundreds of thousands of individuals undergo blood transfusion each year, a procedure that is not without health risks. The emerging fields of tissue engineering and stem cell biology raise hopes for the production of replacement tissues for clinical use. Unfortunately, red blood cells have proven to be notoriously difficult to produce in culture. The Waugh lab, in cooperation with groups in the Department of Pediatrics and at the University of Albany are working to construct flow-based nanostructured devices to help red blood cells mature properly, particularly during the last stages of maturation. An interdisciplinary seed grant (Provost Award) has been received, and a proposal is pending at NIH.
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