Professor, Department of Immunology and Microbial Science
Professor, Department of Chemical Physiology
Faculty, Graduate Program
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.
Ph.D., Biochemistry, University of Illinois at Urbana-Champaign , 1974
M.S., Biochemistry, University of Illinois at Urbana-Champaign , 1971
A.B., Chemistry/Biology, MacMurray College, 1970
Dept. of Biochemistry, Duke University, Postdoctoral Fellow 1974-1978; Dept. of Biol. Chem., Univ. California Los Angeles, Assistant Professor 1978-1981, Associate Professor 1981-1985, Professor and Vice Chair 1985-1990; Cytel Corporation, V.P. Research Development and Board of Directors 1990-1996, Chief Scientific Officer and General Manager and Board of Directors 1996-1999; The Scripps Research Institute, Professor, Depts. of Chemical Physiology and Molecular Biology 1999-2012, Chairman and Professor, Department of Cell and Molecular Biology 2013-2014, Acting President & CEO 2014-present.
Activities: Members Advisory Board, Florida Inventors Hall of Fame (2015 to present); Members Board of Directors, Sanford Consortium for Regenerative Medicine (2014 to present); Chair, ACS Division of Carbohydrate Chemistry (2013-2014); National Academy of Sciences Glycoscience Committee (2011-2012); Principle Investigator/Director, Consortium Functional Glycomics, http://www.functionalglycomics.org (2001-2012); Co-chair Human Glycomics/Proteomics Initiative (HGPI), http://www.hgpi.jp (2005-present); President, The Society for Glycobiology (2002-2003); Editorial board, Glycobiology (1990-present); Scientific Advisory Boards: Neose Technologies Inc (1999-2008), Virdante Pharmaceuticals Inc. (2007-2011), Zacharon (2006-2009), Nexbio (2004-present), Alberta Ingenuity Center for Carbohydrate Science-AICCS, (2003-present), Institute for Biological Sciences-IBS, NRC, Ottawa (2004-present), Joint Center for Structural Genomics-JCSG, PSI Biology (2005-present), and the Boston University Mass Spectrometry Resource, (2006-present)
Awards: United States EPA Green Chemistry Challenge Award, 2000; Barnett Lecture, 2008; Bijvoet Medal, 2008; Karl Meyer Award, 2009; Melville L. Wolfrom Award, 2016.
A complete list of publications can be viewed at http://www.scripps.edu/chemphys/paulson/publications.html
Also available listing at Google Scholar
Macauley MS, Crocker PR, Paulson JC. (2014) Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol. (10):653-66.
Stowell SR, Arthur CM, McBride R, Berger O, Razi N, Heimburg-Molinaro J, Rodrigues LC, Gourdine JP, Noll AJ, von Gunten S, Smith DF, Knirel YA, Paulson JC, Cummings RD. (2014) Microbial glycan microarrays define key features of host-microbial interactions. Nat Chem Biol. 10:470-476.
de Vries RP, Zhu X, McBride R, Rigter A, Hanson A, Zhong G, Hatta M, Xu R, Yu W, Kawaoka Y, de Haan CA, Wilson IA, Paulson JC. (2014) Hemagglutinin receptor specificity and structural analyses of respiratory droplet transmissible H5N1 viruses. J Virol. 88(1):768-773.
Macauley MS, Arlian BM, Rillahan CD, Pang PC, Bortell N, Marcondes MC, Haslam SM, Dell A, Paulson JC. (2014) Systemic blockade of sialylation in mice with a global inhibitor of sialyltransferases. J Biol Chem. 289(51):35149-58.
Macauley, M.S., Pfrengle, F., Rademacher, C., Nycholat, C.M., Gale, A.J., von Drygalski, A., and Paulson, J.C. (2013) Antigenic liposomes displaying CD22 ligands induce antigen-specific B cell apoptosis. J Clin Invest. 123(7):3074-3083.
Wang, Z., Chinoy, Z.S., Ambre, S.G., Peng, W., McBride, R., de Vries, R.P., Glushka, J., Paulson, J.C., and Boons, G.J. (2013) A General Strategy for the Chemoenzymatic Synthesis of Asymmetrically Branched N-Glycans. Science. 341(6144):379-383.
Rillahan, C.D., Schwartz, E., Rademacher, C., McBride, R., Rangarajan, J., Fokin, V.V., and Paulson, J.C. (2013) On-Chip Synthesis and Screening of a Sialoside Library Yields a High Affinity Ligand for Siglec-7. ACS Chem Biol. 8(7):1417-1422.
Kawasaki, N., Vela, J.L., Nycholat, C., Rademacher, C., Khurana, A., van Rooijen, N., Crocker, P.R., Kronenberg, M., and Paulson, J.C. (2013) Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation. Proc Natl Acad Sci U S A. 110(19):7826-31.
Pfrengle, F., Macauley, M.S., Kawasaki, N.,, and Paulson, J.C. (2013) Copresentation of Antigen and Ligands of Siglec-G Induces B Cell Tolerance Independent of CD22. J Immunol. 191(4):1724-1731.
Rillahan, C.D., Antonopoulos, A., Lefort, C.T., Sonon, R., Azadi, A., Ley, K., Dell, A., Haslam, S.M., and Paulson, J.C. (2012) Global metabolic inhibitors of sialyl- and fucosyltransferases remodel the glycome. Nat. Chem. Biol. 8:661-668.
Rillahan, C.D., Schwartz, E., McBride, R., Fokin, V.V., and Paulson, J.C. (2012) Click and Pick: Identification of Sialoside Analogues for Siglec-Based Cell Targeting. Angew Chem Int Ed Engl. 51(44):11014-18
Nycholat, C.M., McBride, R., Ekiert, D.C., Xu, R., Rangarajan, J., Peng, W., Razi, N., Gilbert, M., Wakarchuk, W., Wilson, I.A., and Paulson, J.C. (2012) Recognition of Sialylated Poly-N-acetyllactosamine Chains on N- and O-Linked Glycans by Human and Avian Influenza A Virus Hemagglutinins. Angew Chem Int Ed Engl. 51(20):4860-63
Chen, W.C., Completo, G.C., Sigal, D.S., Crocker, P.R., Saven, A. and Paulson, J.C. (2010) In vivo targeting of B-cell lymphoma with glycan ligands of CD22. Blood. 115(23):4778-86.