James C. Paulson
James C. Paulson obtained his PhD (Biochemistry) in 1974 from the University of Illinois at Champaign-Urbana, and did post-doctoral work at Duke University Medical Centre, in Durham, North Carolina from 1974–78.
From 1978 – 1990 he rose from Assistant Professor to full Professor and vice-chair in the Department of Biological Chemistry at the UCLA School of Medicine where he developed an interest in analysis of receptor specificity of influenza viruses from different host species.
From 1990–1999 he served as Vice President and Member Board of Directors of Cytel Corporation, La Jolla, CA.
From 1999–2012 Professor at the Scripps Research Institute. 2013 to present: Chairman and Professor, Department of Cell and Molecular Biology, Professor, Department of Chemical Physiology at The Scripps Research Institute, La Jolla, CA.
Dr. Paulson served as the President for the Society for Glycobiology from 2002–2003, Director of the Consortium for Functional Glycomics an international consortium of over 500 investigators from 2001–2011, served on National Academy of Sciences Glycoscience Committee from 2011–2012, and currently Chair-elect, ACS Division of Carbohydrate Chemistry.
His current research interests include the roles of glycan binding proteins in the modulation of immune cell signaling, and the influence of receptor specificity in host tropism of mammalian and animal influenza viruses.
Siglecs as sensors of self
The sialic acid binding immunoglobulin lectin (siglec) family of cell adhesion molecules are differentially expressed on white blood cells that confer innate and adaptive immune responses. Because they recognize sialic acid containing glycans as ligands, which are expressed on all mammalian cells, the siglecs are increasingly recognized as receptors that help the immune system distinguish between self and non-self.
To study the roles of ligands in siglec function, we have developed liposomal nanoparticles bearing a multivalent display of specific siglec ligands that can target the desired siglec on living cells in vivo. Using this platform, we have investigated the roles of B cell siglecs, CD22 and Siglec-G in modulation of B cell receptor signaling. CD22 and Siglec-G, are well documented as inhibitory co-receptors of the B cell receptor. We propose that CD22 and Siglec-G cooperate to tolerize B cells that recognize a cell surface autoantigen through their recruitment to the site of the immunological synapse via sialic acid containing ligands on the antigen-bearing cell. The result is induction of a tolerogenic circuit that induces B cell apoptosis. To test this, we generated liposomes displaying an antigen and siglec ligands to mimic a cell expressing an autoantigen.
Remarkably, injection of the liposomes into mice results in induction of apoptosis in reactive B cells, and the mice are then incapable of mounting an antibody response to that antigen in a subsequent challenge. Since development of inhibitory antibodies to FVIII is a serious problem in treatment of hemophilia A patients, we investigated the potential of this approach for inducing tolerance to FVIII in a hemophilia mouse model. Our tolerizing liposomes prevented formation of inhibitory FVIII antibodies, allowing for effective administration of FVIII to hemophilia mice to prevent bleeding. Further studies have documented that the same toleragenic mechanism is induced by natural siglec ligands present on cells that contain a membrane bound antigen.
Thus, we suggest that a major function of the B cell siglecs is to recognize sialic acid as ‘self’, and to induce apoptosis in autoreactive B cells for maintainence of peripheral tolerance. Exploiting this mechanism has therapeutic potential in the areas of autoimmunity, allergies, and biotherapeutics.