Geoffrey S. Kansas, PhD Associate Professor Microbiology-Immunology Molecular Biology of Leukocyte Adhesion and Migration Curricula: Cancer Biology       Cell Biology Immunology and Microbial Pathogenesis Molecular Biology and Genetics E-mail:   gsk@northwestern.edu

There are currently two independent research directions in the lab. The first involves leukocyte adhesion and migration, particularly the biology of selectins. Selectins are a family of three carbohydrate-binding adhesion receptors which play a crucial role in leukocyte recruitment by mediating the inital steps of leukocyte recognition of blood vessel wall. As such, selectins are involved in diseases and disease processes as diverse as inflammation, autoimmunity, and atherosclerosis. The study of selectin biology represents an attractive intersection between immunology, vascular biology and glycobiology.

Our main focus is on identification of enzymes (glycosyltransferases) which play a role in biosynthesis of carbohydrate ligands for selectins, and on how their expression is controlled in T cells. We and other investigators have used mice with targeted disruption of specific genes ("knockout mice") to understand the role of various enzymes in selectin ligand biosynthesis, and we have identified the T Cell Receptor (TCR) and specific cytokine receptors as important in controlling expression of specific enzymes. We are now deciphering the signaling and transcriptional pathways downstream of these receptors, with a focus on Ras and two transcription factors, Stat4 and T-bet, to understand how T cell migration is controlled at the transcriptional level.

The second major area is the biology of plasma cells, antibody-secreting cells about which remarkably little is known. We have used mice with targeted disruption of E- and P-selectins, which harbor extremely elevated levels of IgG plasma cells, to characterize their migration patterns, and to decipher genetic programs which underlie plasma cell differentiation and survival. We are presently focusing on the role of the transcription factor Stat3 in plasma cell development and survival, using mice with a conditional deletion of Stat3 in B cells and other genetically engineered strains. We anticipate that our studies of Stat3 and Ras will intersect in ways that have important implications for understanding multiple myeloma, an incurable disease of malignant plasma cells.

Publications:

Barry SM, Zisoulis DZ, Neal JW, Clipstone NA, Kansas GS. Induction of FucT-VII by the Ras/MAP Kinase cascade in Jurkat T cells. Blood 2003, 102: 1771.

Underhill GH, George D, Bremer EG, Kansas GS. Gene expression profiling reveals a highly specialized genetic program of plasma cells. Blood, 2003, 101: 4013.

White SJ, Underhill GH, Kaplan MH, Kansas GS. Cutting Edge: Differential requirements for Stat4 in expression of glycosyltransferases responsible for selectin ligand formation in Th1 cells. J Immunol, 2001, 167: 628.

Wagers AJ, Waters CM, Stoolman LM, Kansas GS. IL-12 and IL-4 control T cell adhesion to endothelial selectins through opposite effects on FucT-VII gene expression. J Exp Med, 1998, 188, 2225-2230.