|
Faculty
James Paulson
Professor
CHEMICAL PHYSIOLOGY
TSRI - 1999
Joint Appointments Molecular and Experimental Medicine
Education
Ph.D., University of Illinois, 1974
Research Focus
Carbohydrate Binding Proteins in Regulation Of Immune Function
Carbohydrate binding proteins are increasingly recognized to mediate key aspects of cell trafficking and cell signaling in the immune system. At least three families of carbohydrate binding proteins are known to mediate cellular communication among leukocytes. The siglec family now has thirteen members which are expressed on the surface of various white blood cells (e.g. B cells, NK cells, eosinophils, monocytes etc.), and all recognize sialic acid (NeuAc) containing carbohydrate ligands. The best understood for its function is CD22 (siglec-2), which is known to be a negative regulator of B cell receptor signaling. The carbohydrate ligand of CD22 is the sequence NeuAca2,6Gal on N-linked oligosaccharides of glycoproteins. It is required for normal CD22 function since its absence in mutant mice results in marked immuno-suppression in response to vaccination. Our goal is to elucidate the roles of siglec receptors in immune function, and to define biochemical basis for how the interaction with their carbohydrate ligands modulate their function.
Selected References
Crocker, P., Paulson, J.C., & Varki, A. (2007) Siglecs and their roles in the immune system. Nature Reviews Immunology, 4:255-66.
Collins, B.E., Smith, B.A., Bengtson, P., & Paulson, J.C. (2006) Ablation of CD22 in ligand-deficient mice restores B cell receptor signaling. Nature Immunol. 7:199-206
Collins, B.E., Blixt, O., Han, S. Duong, B., Li, H., Nathan, J.K., Bovin, N., & Paulson, J.C. (2006) High Affinity Ligand Probes of CD22 Overcome the Threshold set by cis Ligands to Allow for Binding, Endocytosis and Killing of B cells. J. Immunol. 177:2994-3003.
Han, S., Collins, B.E., Bengtson, P., & Paulson, J.C. (2005) Homo-multimeric Complexes of CD22 in B cells Revealed by Protein-Glycan Crosslinking. Nature Chem. Biol. 1:93-97
|