Biographical Sketch

Dr. Kansas earned his bachelor's degree in biology from Brandeis University in 1978 and his PhD degree from Stanford University in cancer biology in 1984.  His postdoctoral training was with Dr. Morris Dailey at the University of Iowa and subsequently with Dr. Thomas F. Tedder at Harvard Medical School.  Dr. Kansas joined the faculty of Northwestern University in July 1994 and has more than 20 years of experience in leukocyte/endothelial cell adhesion.

Research Description

(i)  Molecular, genetic, cell biologic and in vivo studies of selectins, their ligands, and the enzymes and other proteins which control the functions of selectins.  Control of expression of glycosyltransferases which form selectin ligands,

(ii)  Normal and malignant plasma cell biology, with an emphasis of the role of the transcription factor Stat3 in the differentiation and transformation of IgG plasma cells.

Research Abstract

We have two major research interests.  The first involves leukocyte adhesion and migration, particularly the biology and molecular biology of selectins. Selectins are a group of three carbohydrate-binding proteins expressed on leukocytes (L-selectin), activated endothelium (E- and P-selectin), or activated platelets (P-selectin), that mediate the earliest interactions between leukocytes and endothelium. Selectins play a crucial role in recruitment and migration of all classes of leukocytes to essentially all tissue sites examined. Selectins are therefore involved in the pathogenesis of numerous diseases, including inflammation, autoimmune disease, tumor metastasis, and atherosclerosis.

We are interested in the precise role of specific glycosyltransferases in the biosynthesis of functional selectin ligands.  We are studying certain knockout mice which are missing one or more of these enzymes to understand their role in selectin ligand biosynthesis.  In addition, we are exploring how the expression of these enzymes is controlled, with a particular emphasis on regulation of expression by the TCR and by specific cytokines. 

The second research direction focuses on the biology of plasma cells, terminally differentiated B cells which are responsible for production of antibody.  We have shown that conditional deletion of Stat3 in B cells blocks development of IgG plasma cells, but not plasma cells of other isotypes, thereby defining for the first time the role of a transcription factor in development of a specific plasma cell subset defined by isotype.  We are pursuing the molecular and cellular mechanisms by which Stat3 controls this process.  In addition, due to the likely role of Stat3 in multiple myeloma, a disease of malignant plasma cells which are nearly all IgG isotype, we are pursuing the role of Stat3 in novel mouse models of myeloma.

Publications

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.

Herron MJ, Nelson CM, Larson J, Snapp KR, Kansas GS, Goodman JL.  Intracellular parasitism by the Human Granulocytic Ehrlichiosis Bacterium through the P-selectin ligand PSGL-1.  Science, 2000; 288, 1653.

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

Underhill GH, Kolli KP, Kansas GS.  Complexity within the plasma cell compartment of mice deficient in both E- and P-selectin:  implications for plasma cell differentiation.  Blood, 2003, 102, 4076.

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

Zisoulis, DG, Kansas GS.  H-Ras and PI3K cooperate to induce FucT-VII expression in Jurkat T cells.  J Biol Chem, 2004, 279: 39495.