Our laboratory studies the glycobiology (glycoprotein- and/or glycolipid-dependent biologic processes) inherent to the leukocyte adhesion cascade, which is a critical early component of inflammatory and immune-mediated processes that include atherosclerosis. This cardiovascular disease, commonly referred to as “hardening of the arteries,” is responsible for most “heart attacks” and “strokes,” and is therefore a leading cause of death in westernized countries. Our work focuses on understanding how the selectin-type adhesion molecules and their glycoprotein receptors contribute to the recruitment of various leukocyte types at the sites necessary for atherosclerotic disease development and progression. Particular attention is directed toward understanding the role of two enzymes, alpha(1,3)-fucosyltransferase IV and VII, in the synthesis of active selectin adhesion molecule ligands used for leukocyte homing and trafficking in the atherosclerotic disease process. Our goal is to understand which types of leukocytes use the fucosyltransferases and the selectin adhesion molecule system to contribute to the disease process.

Heart attacks and strokes are generally caused by acute thrombotic events superimposed upon the atherosclerotic process. A number of biologic links between components of the coagulation cascade and the inflammation system have been identified recently, including modulation of the cascade by P-selectin and its fucosylated ligand, PSGL-1. Initial studies demonstrate that mice deficient in the alpha(1,3)-fucosyltransferases IV and VII exhibit an unexpected pro-thrombotic phenotype that does not correlate with the synthesis of selectin ligand activity traditionally ascribed to these enzymes. Thus, a second major research project is to further characterize this pro-thrombotic phenotype and to define the responsible underlying cellular and molecular mechanisms.

These studies utilize a variety of experimental methods and approaches, from classic cellular and molecular biology, to in vitro study of leukocyte adhesion and rolling, to genetic manipulation of mice, and the in vivo study of transgenic and “knockout” mice. Please contact Dr. Homeister to further discuss opportunities in the laboratory.