Gillian Air  /  Sanjay Bidichandani  /  Robert Broyles
Richard Cummings  /  Paul DeAngelis  /  Bryan Fuller  /  Jay Hanas  /  Martin Levine
Guangpu Li  /  Jialing Lin  /  Hiroyuki Matsumoto  /  Ann Louise Olson  /  Karla Rodgers
Robert Steinberg  /  Leon Unger  /  Paul Weigel 

Christopher West  /  James Wyche /  Adam Zlotnick

Glycoconjugate structure/function/biosynthesis; cell adhesion involving lectins and glycoproteins in human inflammation, tumor metastasis and schistosomiasis.

My laboratory is interested in the fundamental biological process by which cells adhere to each other and interact with the extracellular matrix or basement membrane. This research area also relates to processes by which animal pathogens, such as viruses, bacteria, and parasites stick to animal cells and initiate disease. Cell adhesion is an essential prelude to animal cell development, differentiation, tumor metastasis, inflammation and microbial pathogenesis.

Many recent studies indicate that carbohydrate residues within glycoconjugates on the surfaces of cells and in the extracellular matrices are critically involved in cell "stickiness" or cell adhesion phenomena. The overall hypothesis is that these glycoconjugates are recognized and bound by a class of proteins called lectins expressed by a wide variety of cells. There are likely to be many different lectins and many different glycoconjugates involved in cell adhesion. My laboratory is currently studying lectins and glycoconjugates important in a wide variety of cell adhesion phenomena. These include leukocyte recruitment to sites of inflammation in human tissues, adhesion of human rotaviruses to human intestinal cells, structure and immunogenicity of glycoproteins on the surfaces of the human parasitic blood fluke Schistosoma mansoni, binding of lectins to glycoproteins of the extracellular matrix, and the cloning and identification of genes encoding lectins and enzymes (glycosyl transferases) responsible for synthesizing glycoconjugates.

Recent Publications:

Stowell, S.R., Dias-Baruffi, M., Penttila, L., Renkonen, O., Nyame, A.K. and Cummings, R.D. (2004) Human Galectin-1 Recognition of Poly-N-acetyllactosamine and Chimeric Polysaccharides. Glycobiology. 14(2):157-167.

Xia, L., Ju, T., Westmuckett, A., An, G., Ivanciu, L. McDaniel, J.M., Lupu, F., Cummings, R.D. and McEver, R.P. (2004) Defective Angiogenesis and Fatal Embryonic Hemorrhage in Mice Lacking Core-1-derived O-glycans. J. Cell Biol. 164(3):451-9.

van den Berg, T.K., Honing, H., Franke, N., van Remoortere, A., Schiphorst, W.E.C.M., Liu, F.-T., Deelder, A.M., Cummings, R.D., Hokke, C.H., and van Die, I. (2004) LacdiNAc-glycans constitute a parasite pattern for galectin-3-mediated immune recognition.  J. Immunol. 173(3):1902-7.

Nyame, A.K., Kawar, Z.S. and Cummings, R.D. (2004) Antigenic Glycans in Parasitic Infections:  Implications for Vaccines and Diagnostics.  Arch. Biochem. Biophys. 426(2):182-200.

 Otto, V.I., Schürpf, T., Folkers, G., and Cummings, R.D. (2004) Sialylated Complex-type N-glycans Enhance the Signaling Activity of Soluble Intercellular Adhesion Molecule-1 in Mouse Astrocytes. . J. Biol. Chem. 279(34):35201-9.

 Alvarez-Manilla, G., Mattox, S.A., Sanchez-Brambila, G.Y., Zhou, Q., Smith, D.F. and Cummings, R.D.  (2004) Human a-Fucosyltransferases-III and –IV Differentially Affect the Display of Polylactosamines in N-glycans of Chinese Hamster Ovary Cells. Submitted for publication (Revision Pending).

Zhou, Q., Fujimoto, T., McEver, R.P. and Cummings, R.D. a1,3-Fucosylation and Sialylation of Glycoproteins are Differentially Compartmentalized Within Cells. Manuscript in Preparation.

 NguyenNguyen, K., McEver, R.P. and Cummings, R.D. Peptide Specificity of the Cobra Venom Metalloproteinase Mocarhagin. Manuscript in Preparation.

Xia, L., Ramachandran, V., McDaniel, J.M., Cummings, R.D., and Rodger P. McEver.  (2003)  N-terminal Residues in Murine P-selectin Glycoprotein Ligand-1 Required for Binding to Murine P-selectin. Blood. 101(2):552-9.

van Remoortere, A., Bank, C.M.C.Nyame, A.K., Cummings, R.D., Deelder, A.M., van Die, I., (2003) Schistosoma mansoni infected mice produce antibodies that cross-react with plant, insect and human glycoproteins and recognize the truncated biantennary N-glycan Man₃GlcNAc₂-R.  Glycobiology. 13:217-25.

van Die, I., van Vliet, S.J., Schiphorst, W.E.C.M., Bank, C.M.C., Nyame, A.K., Cummings, R.D., Geijtenbeek, T.B.H. and van Kooyk, Y. (2003) The dendritic cell specific C-type lectin DC-SIGN is a receptor for Schistosome mansoni egg antigens and recognizes the glycan antigen Lewis-x.  Glycobiology. 13:471-8.

Leppänen, A., Yago, T., Otto, V.I, McEver, R.P. and Cummings, R.D. (2003) Model Glycosulfopeptides From PSGL-1 Require Tyrosine Sulfation and a Core-2 Branched O-Glycan to Bind to L-selectin. J. Biol. Chem. 278:26391-400.

Dias-Baruffi, M., Zhu, H., Cho, M., Karmaker, S., McEver, R.P. and Cummings, R.D. (2003) Dimeric Galectin-1 Induces Surface Exposure of Phosphatidylserine and Phagocytic Recognition of Leukocytes Without Inducing Apoptosis. J. Biol. Chem. 278:41282-93.

Nyame, K., Doughty, B.L., Wilkins, P.P., and Cummings, R.D. (2003) LDN and LDNF Glycans are (Potential) Targets For Vaccination (Immune Intervention) and Serodiagnosis of Schistosomiasis. Exp. Parasitol. 104(1-2):1-13.

Carylon, J.A., Akkoyunlu, M., Xia, L, Yago, T., Wang, T., Cummings, R.D., McEver, R.P., and Fikrig, E. (2003) Murine neutrophils require a1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophila.  Blood 102(9):3387-95.

Yago, T., Leppänen, A., Carlyon, J.A., Akkoyunlu, Karmaker, S., Fikrig, E., Cummings, R.D., and McEver, R.P. (2003) Structurally distinct requirements for binding of PSGL-1 and sialyl Lewis x to Anaplasma phagocytophila and P-selectin. J. Biol. Chem. 278:37987-97.

Vervelde, L., Bakker, N., Kooyman, F.N.J., Bank, C.M.C., Nyame, A.K., Cummings, R.D. and van Die, I. (2003) Vaccination induced protection of lambs against the parasitic nematode Haemonchus contortus correlates with high IgG antibody responses to the LDNF glycan antigen.  Glycobiology 13(11):795-804.

Xia L, Sperandio M, Yago T, McDaniel JM, Cummings RD, Pearson-White S, Ley K, and McEver RP, 2002: P-selectin glycoprotein ligand-1-deficient mice have impaired leukocyte tethering to E-selectin under flow. J. Clin. Invest. 109:939-950.

Nyame, A.K., Yoshino, T.P. and Cummings, R.D. (2002) Differential Expression of LDN, LDNF and Lewis x Glycan Antigens in Intramolluscan Stages of Schistosoma mansoni.  J. Parasitology 88(5):890-7.

Hicks, A.E.R., Leppänen, A., Cummings, R.D., McEver, R.P., Hellewell, P.G., and Norman, K.E. (2002) Glycosulfopeptides modeled on P-selectin glycoprotein ligand 1 inhibit P-selectin-dependent leukocyte rolling in vivo.  FASEB J. 16(11):1461-2.

Leppänen, A., Penttilä, L., Renkonen, O., McEver, R.P. and Cummings, R.D. (2002) Glycosulfopeptides with O-glycans Containing Sialylated and Polyfucosylated Polylactosamine Bind with Low Affinity to P-selectin. J. Biol. Chem. 277(42):39749-59.

Yago, T., Leppänen, A., Qiu, H., Marcus, W.D., Nollert, M.U., Zhu, C., Cummings, R.D. and McEver, R.P.  (2002) Distinct molecular and cellular contributions to stabilizing selectin-mediated rolling under flow. J. Cell Biol. 158(4):787-99.

Kawar, Z.S., van Die, I., and Cummings, R.D.  (2002) Molecular Cloning and Enzymatic Characterization of a UDPGalNAc:GlcNAc-R b1,4-N-Acetylgalactosaminyltransferase from C. elegans. J. Biol. Chem. 277(38):34924-32.

Kobzdej, M.M.A., Leppänen, A., Ramachandran, V., Cummings, R.D. and McEver, R.P. (2002) Discordant Expression of Selectin Ligands and Sialyl Lewis x-related Epitopes on Murine Myeloid Cells.  Blood. 100(13):4485-94.

Zheng, Q., van Die, I., Barstead, R. and Cummings, R.D. (2002) Cloning and Characterization of a Novel a-1,2-Fucosyltransferase (CE2FT-1) from C. elegans. J. Biol. Chem. 277(42):39823-32.

Ju, T. and Cummings, R.D. (2002) A Unique Molecular Chaperone Cosmc Required for Activity of the Mammalian Core-1 b3-Galactosyltransferase.  Proc. Natl. Acad. Sci. USA 99(26):16613-8.

Walcheck B, Leppanen A, Cummings RD, Knibbs RN, Stoolman LM, Alexander SR, Mattila PE, and McEver RP, 2002: The monoclonal antibody CHO-131 binds to a core 2 O-glycan terminated with sialyl-Lewis x, which is a functional glycan ligand for P-selectin. Blood 99:4063-4069.

Carlos A. Rivera-Marrero, C.A., Newburn, S., Roman, J., Ritzenthaler, J., and Cummings, R.D. (2002)  Identification, Cloning and Expression of a Glycolipid Sulfotransferase in Mycobacterim tuberculosis.  Microbiology. 148:783-92.

 Kelder, B., Erney, R., Kopchick, J., Cummings, R.D. and Prieto, P. (2001) Glycoconjugates in human and transgenic animal milk.  Adv. Exp. Med. Biol. 501:269-78.

Ju Tongzhong, Brewer K, D'Souza A, Cummings R.D., Canfield W.M., 2001: Cloning and Expression Human Core 1 Beta 1,3-Galactosyltransferase. J. Biol. Chem.

Ju Tongzhong, Cummings R.D., Canfield W.M. 2001: Purification, Characterization and Subunit Structure of Rat Core 1 Beta 1,3-Galactosyltransferase. J. Biol. Chem.

Ramachandran V, Yago T, Epperson TK, Kobzdej MMA, Nollert MU, Cummings RD, Zhu C, and McEver RP, 2001. Dimerization of a Selectin and its Ligand Stabilizes Cell Rolling and Enhances Tether Strength in Shear Flow. Proc. Natl Acad. Sci. U.S.A. 98(18):10166-10171.

Eberl M., Langermans J.A., Vervenne R.A., Nyame A.K., Cummings R.D., Thomas A.W., Coulson P.S., Wilson R.A. 2001: Antibodies to glycans dominate the host response to schistosome larvae and eggs: is their role protective or subversive? J Infect Dis. 183(8):1238-47.

van Die, I., Cummings, R.D., van Tetering, A., Hokke, C.H., Koeleman, C.A.M. and van den Eijnden, D.H. 2000: Identification of a novel UDP-Glc:GlcNAc b 1-4-glucosyltransferase in Lymnaea stagnalis that may be involved in the synthesis of complex-type oligosaccharide chains. Glycobiology 10:263-271.

Baxter, J.H., Anderson, S.N., Cummings, R.D., Yeh, J.-C., Snowden, M.K. and Mukerji, P. Human b- and k-casein: a simple purification and their potential anti-infective properties. Submitted for publication.

Epperson, T.K., Patel, K.D., McEver, R.P. and Cummings, R.D. 2000: Noncovalent Dimerization of P-selectin Glycoprotein Ligand-1 and Minimal Determinants for Binding to P-selectin. J. Biol. Chem. 275:7839-7853.

Stray, S.J., Cummings, R.D. and Air, G.M. 2000: Sialic acid-independent infection by influenza virus. Glycobiology 10:649-658.

Keusch, J., Manzella, S.M., Nyame, A.K. Cummings, R.D. and Baenziger, J.U., 2000: Expression cloning of a new member of the ABO blood group glycosyltransferases, iGb₃ synthase, that directs the synthesis of isogloboglycosphingolipids. J. Biol. Chem. 275:25308-25314. 

Keusch, J., Manzella, S.M., Nyame, A.K. Cummings, R.D. and Baenziger, J.U. 2000: Cloning of Gb₃ synthase, the key enzyme in globo-series glycosphingolipid synthesis, predicts a family of a 1,4 glycosyltransferases conserved in plant insects and mammals. J. Biol. Chem. 275:25315-25321.

Nyame, A.K., Leppanen, A.M., Bogitsch B.J. and Cummings, R.D. 2000: Antibody Responses to the Fucosylated LacdiNAc Glycan Antigen in Schistosoma mansoni Infected Mice and Expression of the Glycan Among Schistosomes. Exp. Parasitology . 96:202-212.

Leppanen, A., White, S., Helin, J., McEver, R.P. and Cummings, R.D. 2000: Binding of Glycosulfopeptides to P-selectin Requires Stereospecific Contributions of Individual Tyrosine Sulfate and Sugar Residues. J. Biol. Chem. 275:39569-39578.

Zhu, H., Cho, M., McEver, R.P. and Cummings, R.D. 2000: Dimeric Galectin-1 Induces Apoptotic-Like Changes (Adpararesis) and Phagocytic Recognition of Leukocytes. Submitted for publication.

Kudo, M., McEver, R.P. and Cummings, R.D. 2000: O-Glycosylation of Recombinant PSGL-1 Bound by P-selectin. Submitted for publication.

Leppänen, A., Mehta, P., Ouyang, Y.B., Ju, T., Helin, J., Moore, K.L., van Die, I., Canfield, W.M., McEver, R.P. and Cummings, R.D. 1999: A Novel Glycosulfopeptide Binds to P-selectin and Inhibits Leukocyte Adhesion to P-selectin. J. Biol. Chem. 274:24838-24848.

Ramachandran, V., Matthias, U. , Nollert, M.U., Qui, H., Liu, W.-J., Cummings, R.D. Zhu, C., and McEver, R.P., 1999: Substitutions of Tyrosines in P-Selectin Glycoprotein Ligand-1 Affect Distinct Kinetic and Mechanical Properties of Bonds with P- and L-Selectin. Proc. Natl. Acad. Sci. U.S.A. 96(24):13771-13776.

Zhu, H., Cho, M., Brower, C., McEver, R.P. and Cummings, R.D. 1999: Apoptotic-Like Changes (Adpararesis) and Phagocytic Recognition of Leukocytes Induced by Dimeric Galectin-1. Submitted for publication.

Cummings, R.D. and Canfield, W.M. 1999: N-Glycosylation in The Encyclopedia of Molecular Biology (T.E. Creighton, Ed), John Wiley and Sons, Inc., New York.

Cummings, R.D. and A.K. Nyame 1999: Schistosome Glycoconjugates. Biochem. Biophys. Acta. 1455:363-374.

Cummings, R.D. 1999: Structure and Function of the Selectin Ligand PSGL-1. Invited Review for Brazilian J. Med. Biol. Res. 32:519-528.

Kwame, A.K., Leppanen, A.M., DeBose-Boyd, R. and Cummings, R.D. 1999: Mice Infected with Schistosoma mansoni Generate Antibodies to LacdiNAc GalNAcb1® 4GlcNAc) Determinants. Glycobiology 9:1029-1035.

Mehta, P., Cummings, R.D. and McEver, R.P. 1998: Affinity and kinetic analysis of P-selectin binding to P-selectin glycoprotein ligand-1. J. Biol. Chem. 273:32506-13.

Liu, W.-J., Ramachandran, V. Kang, J., Kishimoto, T.K., Cummings, R.D. and McEver, R.P., 1998: Identification of N-Terminal Residues on P-selectin Glycoprotein Ligand-1 Required for Binding to P-selectin. J. Biol. Chem. 273:7078-7087.

DeBose-Boyd, R.A., Nyame, A.K., and Cummings, R.D., 1998: Molecular Cloning and Characterization of an a1,3-Fucosyltransferase CEFT-1 from Caenorhabditis elegans. Glycobiology 8:905-917.

DeBose-Boyd, R.A., Nyame, A.K., Jasmer, D.P. and Cummings, R.D., 1998: The Ruminant Parasite Haemonchus contortus Expresses an a1,3-Fucosyltransferase Capable of Synthesizing the Lewis x and Sialyl Lewis x Antigens. Glycoconj. J. 15:789-798.

Nyame, A.K., DeBose-Boyd, R.A., Long, T.D., Tsang, V.C.W and Cummings, R.D., 1998: Expression of Le^x Antigen in Schistosoma japonicum and S. haematobium and Immune Response to Le^x in Infected Animals: Lack of Le^x Expression in Other Trematodes and Nematodes. Glycobiology. 8:615-624.

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