Ajit Varki

Summary

Affiliation: University of California
Country: USA

Publications

  1. doi request reprint Biomedical differences between human and nonhuman hominids: potential roles for uniquely human aspects of sialic acid biology
    Nissi M Varki
    Glycobiology Research and Training Center, University of California at San Diego, La Jolla, 92093 0687, USA
    Annu Rev Pathol 6:365-93. 2011
  2. ncbi request reprint Diversity in cell surface sialic acid presentations: implications for biology and disease
    Nissi M Varki
    Department of Pathology, Glycobiology Research and Training Center, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Lab Invest 87:851-7. 2007
  3. ncbi request reprint Siglecs--the major subfamily of I-type lectins
    Ajit Varki
    Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305 8568, Japan
    Glycobiology 16:1R-27R. 2006
  4. pmc Evolution of siglec-11 and siglec-16 genes in hominins
    Xiaoxia Wang
    Glycobiology Research and Training Center, University of California at San Diego, San Diego, CA, USA
    Mol Biol Evol 29:2073-86. 2012
  5. ncbi request reprint Human-specific regulation of alpha 2-6-linked sialic acids
    Pascal Gagneux
    Glycobiology Research and Training Center, Department of Medicine, University of California San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 278:48245-50. 2003
  6. pmc Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid N-glycolylneuraminic acid
    Rachel E Taylor
    Department of Medicine, Skaggs School of Pharmacy and PharmaceuticalSciences, University of California, San Diego, La Jolla, CA 92093, USA
    J Exp Med 207:1637-46. 2010
  7. ncbi request reprint A human-specific gene in microglia
    Toshiyuki Hayakawa
    Glycobiology Research and Training Center, University of California at San Diego, La Jolla, CA 92093, USA
    Science 309:1693. 2005
  8. pmc Inverse hormesis of cancer growth mediated by narrow ranges of tumor-directed antibodies
    Oliver M T Pearce
    Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Department of Pathology, University of California, San Diego, La Jolla, CA 92093
    Proc Natl Acad Sci U S A 111:5998-6003. 2014
  9. pmc Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5
    Aaron F Carlin
    Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
    J Exp Med 206:1691-9. 2009
  10. pmc Cross-comparison of protein recognition of sialic acid diversity on two novel sialoglycan microarrays
    Vered Padler-Karavani
    Department of Medicine and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 287:22593-608. 2012

Collaborators

Detail Information

Publications108 found, 100 shown here

  1. doi request reprint Biomedical differences between human and nonhuman hominids: potential roles for uniquely human aspects of sialic acid biology
    Nissi M Varki
    Glycobiology Research and Training Center, University of California at San Diego, La Jolla, 92093 0687, USA
    Annu Rev Pathol 6:365-93. 2011
    ..We also discuss the metabolic incorporation of a diet-derived nonhuman sialic acid, which generates a novel xeno-autoantigen reaction, and chronic inflammation known as xenosialitis...
  2. ncbi request reprint Diversity in cell surface sialic acid presentations: implications for biology and disease
    Nissi M Varki
    Department of Pathology, Glycobiology Research and Training Center, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Lab Invest 87:851-7. 2007
    ..This review will provide some examples of these diverse roles of Sias and briefly address immunohistochemical approaches to their detection...
  3. ncbi request reprint Siglecs--the major subfamily of I-type lectins
    Ajit Varki
    Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305 8568, Japan
    Glycobiology 16:1R-27R. 2006
    ..This article provides an overview of historical and current information about the Siglecs...
  4. pmc Evolution of siglec-11 and siglec-16 genes in hominins
    Xiaoxia Wang
    Glycobiology Research and Training Center, University of California at San Diego, San Diego, CA, USA
    Mol Biol Evol 29:2073-86. 2012
    ....
  5. ncbi request reprint Human-specific regulation of alpha 2-6-linked sialic acids
    Pascal Gagneux
    Glycobiology Research and Training Center, Department of Medicine, University of California San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 278:48245-50. 2003
    ....
  6. pmc Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid N-glycolylneuraminic acid
    Rachel E Taylor
    Department of Medicine, Skaggs School of Pharmacy and PharmaceuticalSciences, University of California, San Diego, La Jolla, CA 92093, USA
    J Exp Med 207:1637-46. 2010
    ..As the flora residing in the nasopharynx of infants can be in contact with ingested food, we propose a novel model for how NTHi and dietary Neu5Gc cooperate to generate anti-Neu5Gc antibodies in humans...
  7. ncbi request reprint A human-specific gene in microglia
    Toshiyuki Hayakawa
    Glycobiology Research and Training Center, University of California at San Diego, La Jolla, CA 92093, USA
    Science 309:1693. 2005
    ..SIGLEC11 is expressed in human but not in chimpanzee brain microglia. Further studies will determine if this event was related to the evolution of Homo...
  8. pmc Inverse hormesis of cancer growth mediated by narrow ranges of tumor-directed antibodies
    Oliver M T Pearce
    Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Department of Pathology, University of California, San Diego, La Jolla, CA 92093
    Proc Natl Acad Sci U S A 111:5998-6003. 2014
    ..Similar findings were made in a human tumor xenograft model using a narrow range of doses of a monoclonal antibody currently in clinical use. These findings may have implications for the etiology, prevention, and treatment of cancer. ..
  9. pmc Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5
    Aaron F Carlin
    Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
    J Exp Med 206:1691-9. 2009
    ..We conclude that protein-mediated functional engagement of an inhibitory host lectin receptor promotes bacterial innate immune evasion...
  10. pmc Cross-comparison of protein recognition of sialic acid diversity on two novel sialoglycan microarrays
    Vered Padler-Karavani
    Department of Medicine and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 287:22593-608. 2012
    ..They also highlight important challenges and questions for the future of glycan array technology and suggest that glycan arrays with similar glycan structures cannot be simply assumed to give similar results...
  11. ncbi request reprint Mechanism of uptake and incorporation of the non-human sialic acid N-glycolylneuraminic acid into human cells
    Muriel Bardor
    Glycobiology Research and Training Center, Department of Medicine, University of California San Diego, La Jolla, California, 92093 0687, USA
    J Biol Chem 280:4228-37. 2005
    ..The approach could, thus, potentially be generalized to any small molecule that has a specific lysosomal transporter but not a plasma membrane transporter...
  12. ncbi request reprint 9-O-acetylation of exogenously added ganglioside GD3. The GD3 molecule induces its own O-acetylation machinery
    Helen Y Chen
    Glycobiology Research and Training Center, Department of Medicine, University of California San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 281:7825-33. 2006
    ....
  13. doi request reprint Quantum dot nanometal surface energy transfer based biosensing of sialic acid compositions and linkages in biological samples
    Raghavendra Kikkeri
    Glycobiology Research and Training Center, Department of Medicine, University of California, San Diego, La Jolla, California, United States
    Anal Chem 85:3864-70. 2013
    ....
  14. pmc NeuA sialic acid O-acetylesterase activity modulates O-acetylation of capsular polysaccharide in group B Streptococcus
    Amanda L Lewis
    Glycobiology Research and Training Center, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093 0687, USA
    J Biol Chem 282:27562-71. 2007
    ....
  15. pmc Sexual selection by female immunity against paternal antigens can fix loss of function alleles
    Darius Ghaderi
    Center for Academic Research and Training in Anthropogeny, Glycobiology Research and Training Center and Departments of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 108:17743-8. 2011
    ..Similar circumstances existed when the CMAH null allele was polymorphic in ancestral hominins, just before the divergence of Homo from australopithecines...
  16. ncbi request reprint Human-specific expression of Siglec-6 in the placenta
    Els C M Brinkman-Van der Linden
    Glycobiology Research and Training Center, Department of Medicine, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Glycobiology 17:922-31. 2007
    ..The leptin-binding ability of Siglec-6 is also consistent with this hypothesis, as leptin-deficient mice have increased parturition times...
  17. pmc Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas
    Mark Wahrenbrock
    Department of Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California 92093 0687, USA
    J Clin Invest 112:853-62. 2003
    ..These data may also explain why heparin ameliorates Trousseau syndrome, while vitamin K antagonists that merely depress thrombin production do not...
  18. pmc Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response
    Aaron F Carlin
    Department of Medicine, Pediatrics, and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093 0687, USA
    Blood 113:3333-6. 2009
    ..Thus, GBS can impair neutrophil defense functions by coopting a host inhibitory receptor via sialoglycan molecular mimicry, a novel mechanism of bacterial immune evasion...
  19. ncbi request reprint System-wide genomic and biochemical comparisons of sialic acid biology among primates and rodents: Evidence for two modes of rapid evolution
    Tasha K Altheide
    Glycobiology Research and Training Center, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 281:25689-702. 2006
    ....
  20. pmc Relative over-reactivity of human versus chimpanzee lymphocytes: implications for the human diseases associated with immune activation
    Paula C Soto
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    J Immunol 184:4185-95. 2010
    ..Taken together, these data may help explain human propensities for diseases associated with excessive activation of the adaptive immune system...
  21. ncbi request reprint The group B streptococcal sialic acid O-acetyltransferase is encoded by neuD, a conserved component of bacterial sialic acid biosynthetic gene clusters
    Amanda L Lewis
    Division of Biological Sciences, University of California San Diego, 92093 0687, USA
    J Biol Chem 281:11186-92. 2006
    ..These studies define a molecular genetic approach for the selective elimination of GBS Sia O-acetylation without concurrent loss of sialylation, a key to further studies addressing the role(s) of this modification in bacterial virulence...
  22. doi request reprint alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo
    Maria Hedlund
    Glycobiology Research and Training Center, Department of Medicine, University of California, San Diego, La Jolla, California 92093 0687, USA
    Cancer Res 68:388-94. 2008
    ..These findings indicate a role for ST6Gal-I as a mediator of tumor progression, with its expression causing a less differentiated phenotype, via enhanced beta1-integrin function...
  23. ncbi request reprint A uniquely human consequence of domain-specific functional adaptation in a sialic acid-binding receptor
    Justin L Sonnenburg
    Glycobiology Research and Training Center, Department of Medicine, University of California, San Diego, La Jolla, CA 92093 0687, USA
    Glycobiology 14:339-46. 2004
    ..Such domain-specific divergences should also be considered in upcoming comparisons of human and chimpanzee genomes...
  24. pmc Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins
    Darius Ghaderi
    Glycobiology Research and Training Center, Department of Medicine and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, USA
    Nat Biotechnol 28:863-7. 2010
    ..Our findings may be relevant to improving the half-life, efficacy and immunogenicity of glycoprotein therapeutics...
  25. ncbi request reprint Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates
    Takashi Angata
    Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, 1 1 1 Umezono, Tsukuba, Ibaraki 305 8568, Japan
    FASEB J 20:1964-73. 2006
    ..The "essential arginine" critical for sialic acid recognition in both Siglec-14 and Siglec-5 is present in humans but mutated in almost all great ape alleles...
  26. ncbi request reprint Differential metastasis inhibition by clinically relevant levels of heparins--correlation with selectin inhibition, not antithrombotic activity
    Jennifer L Stevenson
    Glycobiology Research and Training Center, Department of Medicine, Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, California 92093 0687, USA
    Clin Cancer Res 11:7003-11. 2005
    ..We studied metastasis inhibition by clinically relevant levels of various heparins and investigated the structural basis for selectin inhibition differences...
  27. ncbi request reprint Heparin attenuates metastasis mainly due to inhibition of P- and L-selectin, but non-anticoagulant heparins can have additional effects
    Jennifer L Stevenson
    Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA
    Thromb Res 120:S107-11. 2007
    ..However, such heparins could have further effects at higher doses...
  28. pmc Rapid evolution of binding specificities and expression patterns of inhibitory CD33-related Siglecs in primates
    Vered Padler-Karavani
    39500 Gilman Dr, University of California at San Diego, La Jolla, CA 92093 0687, USA
    FASEB J 28:1280-93. 2014
    ....
  29. pmc ABO blood group glycans modulate sialic acid recognition on erythrocytes
    Miriam Cohen
    Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA
    Blood 114:3668-76. 2009
    ..Thus, ABH antigens can noncovalently alter the presentation of other cell surface glycans to cognate-binding proteins, without themselves being a direct ligand...
  30. pmc Evolution of human-chimpanzee differences in malaria susceptibility: relationship to human genetic loss of N-glycolylneuraminic acid
    Maria J Martin
    Glycobiology Research and Training Center and Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 102:12819-24. 2005
    ..These results also have implications for the prehistory of hominids and for the genetic origins and recent emergence of P. falciparum as a major human pathogen...
  31. pmc Diversity in specificity, abundance, and composition of anti-Neu5Gc antibodies in normal humans: potential implications for disease
    Vered Padler-Karavani
    Glycobiology Research and Training Center and Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Glycobiology 18:818-30. 2008
    ....
  32. pmc O-Acetylation of sialic acid on Group B Streptococcus inhibits neutrophil suppression and virulence
    Shannon Weiman
    Department of Pediatrics, Glycobiology Research and Training Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0687, U S A
    Biochem J 428:163-8. 2010
    ..In vitro and in vivo assays demonstrate that this subtle modification attenuates GBS Sia-mediated neutrophil suppression and animal virulence...
  33. pmc Lectin galactoside-binding soluble 3 binding protein (LGALS3BP) is a tumor-associated immunomodulatory ligand for CD33-related Siglecs
    Heinz Laubli
    From the Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093
    J Biol Chem 289:33481-91. 2014
    ..These findings suggest a novel immunoinhibitory function for LGALS3BP that might be important for immune evasion of tumor cells during cancer progression. ..
  34. pmc CD33/Siglec-3 binding specificity, expression pattern, and consequences of gene deletion in mice
    Els C M Brinkman-Van der Linden
    Department of Medicine, University of California, San Diego, La Jolla, California 92093 0687, USA
    Mol Cell Biol 23:4199-206. 2003
    ....
  35. pmc Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils
    Mai Zhang
    Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, and Biomedical Sciences Graduate Program, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Blood 109:4280-7. 2007
    ....
  36. pmc Evidence for a novel human-specific xeno-auto-antibody response against vascular endothelium
    Tho Pham
    Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093 0687, USA
    Blood 114:5225-35. 2009
    ..In the case of atherosclerosis, Neu5Gc is present both in endothelium overlying plaques and in subendothelial regions, providing multiple pathways for accelerating inflammation in this disease...
  37. pmc Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression
    Maria Hedlund
    Glycobiology Research and Training Center and Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 105:18936-41. 2008
    ....
  38. pmc Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer
    Vered Padler-Karavani
    University of California at San Diego, CA, USA
    Cancer Res 71:3352-63. 2011
    ..Such xeno-autoantibodies and xeno-autoantigens have potential for novel diagnostics, prognostics, and therapeutics in human carcinomas...
  39. pmc Loss of Siglec expression on T lymphocytes during human evolution
    Dzung H Nguyen
    Glycobiology Research and Training Center and Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 103:7765-70. 2006
    ....
  40. pmc Group B streptococcal capsular sialic acids interact with siglecs (immunoglobulin-like lectins) on human leukocytes
    Aaron F Carlin
    Department of Pediatrics, Division of Pharmacology and Drug Discovery, University of California, San Diego School of Medicine, Cellular and Molecular Medicine East, La Jolla, CA 92093 0687, USA
    J Bacteriol 189:1231-7. 2007
    ..Thus, production of Sia-capped bacterial polysaccharide capsules that mimic human cell surface glycans in order to engage CD33rSiglecs may be an example of a previously unrecognized bacterial mechanism of leukocyte manipulation...
  41. pmc N-glycolylneuraminic acid deficiency in mice: implications for human biology and evolution
    Maria Hedlund
    Glycobiology Research and Training Center, Department of Medicine, University of California San Diego, La Jolla, CA 92093 0687, USA
    Mol Cell Biol 27:4340-6. 2007
    ..Adult animals also showed delayed skin wound healing. Loss of Neu5Gc in hominid ancestors approximately 2 to 3 million years ago likely had immediate and long-term consequences for human biology...
  42. pmc Metabolism of vertebrate amino sugars with N-glycolyl groups: mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid
    Kalyan Banda
    Department of Medicine, University of California San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 287:28852-64. 2012
    ..This human-like model can be used to elucidate specific mechanisms of Neu5Gc delivery from the gut to tissues, as well as general mechanisms of metabolism of ingested sialic acids...
  43. pmc Innovations in host and microbial sialic acid biosynthesis revealed by phylogenomic prediction of nonulosonic acid structure
    Amanda L Lewis
    Glycobiology Research and Training Center, Departments of Pediatrics, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 106:13552-7. 2009
    ..Together, these data indicate that some of the long-standing paradigms in Sia biology should be reconsidered in a wider evolutionary context of the extended family of NulO sugars...
  44. ncbi request reprint Effects of natural human antibodies against a nonhuman sialic acid that metabolically incorporates into activated and malignant immune cells
    Dzung H Nguyen
    Glycobiology Research and Training Center, and Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    J Immunol 175:228-36. 2005
    ..Further studies are needed to determine whether deposition of natural GcIg and complement can also target healthy proliferating immune cells for death in vivo following incorporation of dietary Neu5Gc...
  45. pmc Colloquium paper: uniquely human evolution of sialic acid genetics and biology
    Ajit Varki
    Center for Academic Research and Training in Anthropogeny, Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 107:8939-46. 2010
    ....
  46. pmc Sensitive and specific detection of the non-human sialic Acid N-glycolylneuraminic acid in human tissues and biotherapeutic products
    Sandra L Diaz
    Departments of Medicine, Pathology and Cellular and Molecular Medicine, Glycobiology Research and Training Center, School of Medicine, University of California San Diego, La Jolla, California, United States of America
    PLoS ONE 4:e4241. 2009
    ..However, prior preparations of such antibodies (including our own) suffered from some non-specificity, as well as some cross-reactivity with the human sialic acid N-acetylneuraminic acid (Neu5Ac)...
  47. pmc SIGLEC12, a human-specific segregating (pseudo)gene, encodes a signaling molecule expressed in prostate carcinomas
    Nivedita Mitra
    Glycobiology Research and Training Center, Department of Medicine, University of California at San Diego, La Jolla, California 92093, USA
    J Biol Chem 286:23003-11. 2011
    ..Polymorphic expression of Siglec-XII in humans thus has implications for prostate cancer biology and therapeutics...
  48. pmc Metabolism of vertebrate amino sugars with N-glycolyl groups: elucidating the intracellular fate of the non-human sialic acid N-glycolylneuraminic acid
    Anne K Bergfeld
    Department of Medicine, Glycobiology Research and Training Center, University of California San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 287:28865-81. 2012
    ..Finally, we demonstrate that the proposed degradative pathway is partially reversible, showing that N-glycolylmannosamine and N-glycolylglucosamine (but not glycolate) can serve as precursors for biosynthesis of endogenous Neu5Gc...
  49. pmc Metabolism of vertebrate amino sugars with N-glycolyl groups: resistance of ╬▒2-8-linked N-glycolylneuraminic acid to enzymatic cleavage
    Leela R L Davies
    Department of Medicine, Glycobiology Research and Training Center, University of California San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 287:28917-31. 2012
    ..In keeping with this, polymers of N-propionylneuraminic acid are sensitive to sialidases. Resistance of Neu5Gc-containing polySia to sialidases provides a potential explanation for the rarity of Neu5Gc in the vertebrate brain...
  50. pmc Multifarious roles of sialic acids in immunity
    Ajit Varki
    Glycobiology Research and Training Center, Department of Medicine, University of California at San Diego, La Jolla, 92093 0687, USA
    Ann N Y Acad Sci 1253:16-36. 2012
    ....
  51. ncbi request reprint Genes modulated by expression of GD3 synthase in Chinese hamster ovary cells. Evidence that the Tis21 gene is involved in the induction of GD3 9-O-acetylation
    Honoo Satake
    Glycobiology Research and Training Center, Department of Medicine, University of California, San Diego, La Jolla 92093 0687, USA
    J Biol Chem 278:7942-8. 2003
    ..This indicates separate machineries for 9-O-acetylation on alpha2-8-linked sialic acids of gangliosides and on alpha2-6-linked sialic acids on N-glycans...
  52. pmc Generation of mice deficient for macrophage galactose- and N-acetylgalactosamine-specific lectin: limited role in lymphoid and erythroid homeostasis and evidence for multiple lectins
    Thandi M Onami
    Molecular Biology Section, Division of Biology, Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
    Mol Cell Biol 22:5173-81. 2002
    ..Experiments are presented that indicate the existence of another galactose- and N-acetylgalactosamine-recognizing lectin distinct from mMGL. This may explain the absence of a strong phenotype in mMGL-deficient mice...
  53. pmc Immunomodulatory activity of extracellular Hsp70 mediated via paired receptors Siglec-5 and Siglec-14
    Jerry J Fong
    Glycobiology Research and Training Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA Department of Cellular and Molecular Medicine, Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA
    EMBO J 34:2775-88. 2015
    ....
  54. pmc A red meat-derived glycan promotes inflammation and cancer progression
    Annie N Samraj
    Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093
    Proc Natl Acad Sci U S A 112:542-7. 2015
    ..This mechanism might also contribute to other chronic inflammatory processes epidemiologically associated with red meat consumption. ..
  55. pmc Specific inactivation of two immunomodulatory SIGLEC genes during human evolution
    Xiaoxia Wang
    Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 109:9935-40. 2012
    ..Taken together, these data suggest that genetic elimination of Siglec-13 and/or Siglec-17 represents signatures of infectious and/or other inflammatory selective processes contributing to population restrictions during hominin origins...
  56. pmc Expression of Siglec-11 by human and chimpanzee ovarian stromal cells, with uniquely human ligands: implications for human ovarian physiology and pathology
    Xiaoxia Wang
    Center for Academic Research and Training in Anthropogeny, Department of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Glycobiology 21:1038-48. 2011
    ..Siglec-11 expression was also found on human ovarian stromal tumors and in polycystic ovarian syndrome, a human-specific disease. These results indicate potential roles for Siglec-11 in ovarian physiology and human evolution...
  57. pmc Genetic and biochemical modulation of sialic acid O-acetylation on group B Streptococcus: phenotypic and functional impact
    Shannon Weiman
    Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093 0687, USA
    Glycobiology 19:1204-13. 2009
    ..We conclude that native GBS likely expresses a phenotype of intermediate Sia O-acetylation to strike a balance between competing selective pressures present in the host environment...
  58. ncbi request reprint Cell surface sialic acids do not affect primary CD22 interactions with CD45 and surface IgM nor the rate of constitutive CD22 endocytosis
    Mai Zhang
    Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093 0687, USA
    Glycobiology 14:939-49. 2004
    ..The effects on antibody-mediated endocytosis could be of relevance to immunotoxin treatment of lymphomas...
  59. pmc Cell-intrinsic mechanism involving Siglec-5 associated with divergent outcomes of HIV-1 infection in human and chimpanzee CD4 T cells
    Paula C Soto
    Department of Pathology, University of California, San Diego and Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA
    J Mol Med (Berl) 91:261-70. 2013
    ..Taken together, our results suggest that Siglec-5 expression protects T cells from HIV-1- and apoptosis-induced cell death and contributes to the different outcomes of HIV-1 infection in humans and chimpanzees...
  60. pmc A simple method for assessment of human anti-Neu5Gc antibodies applied to Kawasaki disease
    Vered Padler-Karavani
    Glycobiology Research and Training Center, Department of Medicine, University of California San Diego, La Jolla, California, United States of America
    PLoS ONE 8:e58443. 2013
    ..Both assays revealed an elevated response in acute KD patients with normal coronaries compared to patients with aneurysm or dilated coronaries. Implications of these findings are discussed...
  61. pmc Heparin's anti-inflammatory effects require glucosamine 6-O-sulfation and are mediated by blockade of L- and P-selectins
    Lianchun Wang
    Department of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0687, USA
    J Clin Invest 110:127-36. 2002
    ..Such analogs may prove useful as therapeutically effective inhibitors of inflammation...
  62. ncbi request reprint Genetically altered mice with different sialyltransferase deficiencies show tissue-specific alterations in sialylation and sialic acid 9-O-acetylation
    Laura T Martin
    Glycobiology Research and Training Center, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA
    J Biol Chem 277:32930-8. 2002
    ..These data demonstrate selective regulation of sialylation and 9-O-acetylation, point to cell types with potential physiological defects in null animals, and show in vivo evidence for competition between Golgi enzymes...
  63. doi request reprint Multiple changes in sialic acid biology during human evolution
    Ajit Varki
    Center for Academic Research and Training in Anthropogeny, Department of Medicine, University of California, San Diego, 9500 Gilman Dr MC 0687, La Jolla, CA 92093 0687, USA
    Glycoconj J 26:231-45. 2009
    ..As humans also have varying and sometime high levels of circulating anti-Neu5Gc antibodies, there are implications for biotechnology products, and for some human diseases associated with chronic inflammation...
  64. doi request reprint The sialome--far more than the sum of its parts
    Miriam Cohen
    Glycobiology Research and Training Center, Department of Medicine, University of California, San Diego, La Jolla, California, USA
    OMICS 14:455-64. 2010
    ..Understanding the full complexity of the sialome thus requires combined analyses at multiple levels, that is, the sialome is far more than the sum of its parts...
  65. ncbi request reprint Heparin inhibition of selectin-mediated interactions during the hematogenous phase of carcinoma metastasis: rationale for clinical studies in humans
    Nissi M Varki
    Department of Medicine, Cancer Center, University of California, San Diego, La Jolla, California 92093 0687, USA
    Semin Thromb Hemost 28:53-66. 2002
    ..A suggested clinical trial is outlined...
  66. pmc Large-scale sequencing of the CD33-related Siglec gene cluster in five mammalian species reveals rapid evolution by multiple mechanisms
    Takashi Angata
    Glycobiology Research and Training Center, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Proc Natl Acad Sci U S A 101:13251-6. 2004
    ....
  67. ncbi request reprint Glycan-based interactions involving vertebrate sialic-acid-recognizing proteins
    Ajit Varki
    Department of Medicine, Glycobiology Research and Training Center, University of California at San Diego, La Jolla, California 92093 0687, USA
    Nature 446:1023-9. 2007
    ..Studying the roles of such proteins in vertebrates has improved our understanding of normal physiology, disease and human evolution...
  68. pmc Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis
    Lubor Borsig
    Glycobiology Research and Training Center and the Cancer Center, Department of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Proc Natl Acad Sci U S A 99:2193-8. 2002
    ..Thus, L-selectin on neutrophils, monocytes, and/or NK cells has a role in facilitating metastasis, acting beyond the early time points wherein P-selectin mediates interactions of platelet with tumor cells...
  69. pmc Metabolism of vertebrate amino sugars with N-glycolyl groups: incorporation of N-glycolylhexosamines into mammalian glycans by feeding N-glycolylgalactosamine
    Anne K Bergfeld
    Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 287:28898-916. 2012
    ..This study demonstrates that mammalian N-acetylhexosamine pathways and glycan assembly are surprisingly tolerant toward the N-glycolyl substituent...
  70. ncbi request reprint Myeloid precursors and acute myeloid leukemia cells express multiple CD33-related Siglecs
    Dzung H Nguyen
    Glycobiology Research and Training Center, University of California, San Diego, La Jolla, USA
    Exp Hematol 34:728-35. 2006
    ..We sought to characterize the spectrum of expression of the other CD33rSiglecs on bone marrow precursors and AML cells and asked if they can potentially serve as targets for therapy...
  71. ncbi request reprint Cloning and characterization of human Siglec-11. A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia
    Takashi Angata
    Glycobiology Research and Training Center, Department of Medicine, University of California, San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 277:24466-74. 2002
    ....
  72. ncbi request reprint Multiple hepatic receptors cooperate to eliminate secretory mucins aberrantly entering the bloodstream: are circulating cancer mucins the "tip of the iceberg"?
    Mark G Wahrenbrock
    Glycobiology Research and Training Center, Department of Medicine, University of California, San Diego, California 92093 0687, USA
    Cancer Res 66:2433-41. 2006
    ..quot; Such aberrantly circulating mucins could play pathologic roles not only in cancer but also during injury or inflammation of hollow organs and in liver disease...
  73. pmc Pancreatic beta-cell failure in obese mice with human-like CMP-Neu5Ac hydroxylase deficiency
    Sarah Kavaler
    Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0673, USA
    FASEB J 25:1887-93. 2011
    ..This may lend insight into the pathogenesis of type 2 diabetes in obese humans...
  74. pmc Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands
    Lesley G Ellies
    Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, 9500 Gilman Drive 0625, University of California San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 99:10042-7. 2002
    ..Oligosaccharide branch-specific sialylation by the ST3Gal-IV sialyltransferase is required to sustain the physiologic half-life of murine hemostatic components and may be an important modifier of plasma VWF level in humans...
  75. ncbi request reprint Recombinant influenza C hemagglutinin-esterase as a probe for sialic acid 9-O-acetylation
    Laura T Martin
    Departments of Medicine and Cellular Molecular Medicine, University of California San Diego, School of Medicine, La Jolla, California 92093, USA
    Methods Enzymol 363:489-98. 2003
  76. pmc Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid
    Pam Tangvoranuntakul
    Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Proc Natl Acad Sci U S A 100:12045-50. 2003
    ..Potential implications for human diseases are briefly discussed...
  77. pmc Symbol nomenclature for glycan representation
    Ajit Varki
    Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093 0687, USA
    Proteomics 9:5398-9. 2009
    ..We also note that >200 illustrations in the second edition have already been published using our nomenclature and are available for download at PubMed...
  78. pmc Overview of glycoconjugate analysis
    Ajit Varki
    University of California San Diego, La Jolla, California, USA
    Curr Protoc Protein Sci . 2009
    ..A glossary of terms used in glycobiology is also provided...
  79. ncbi request reprint Effects of sialic acid substitutions on recognition by Sambucus nigra agglutinin and Maackia amurensis hemagglutinin
    Els C M Brinkman-Van der Linden
    Glycobiology Research and Training Center, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Anal Biochem 303:98-104. 2002
  80. pmc O-acetylation of GD3: an enigmatic modification regulating apoptosis?
    Helen Y Chen
    Glycobiology Research and Training Center, Department of Medicine and Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA
    J Exp Med 196:1529-33. 2002
  81. ncbi request reprint Nothing in glycobiology makes sense, except in the light of evolution
    Ajit Varki
    Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Cell 126:841-5. 2006
    ..The remarkable structural diversity of glycans in nature, and their roles in cellular processes, host-pathogen interactions, biological diversity and speciation can be explained by evolutionary processes...
  82. doi request reprint Metabolic radiolabeling of animal cell glycoconjugates
    Sandra Diaz
    University of California San Diego, La Jolla, CA, USA
    Curr Protoc Mol Biol . 2009
    ..Following metabolic labeling, the radioactive glycoconjugate of interest is isolated, individual glycosylation sites are identified and separated if necessary, and the labeled glycans are subjected to structural analysis...
  83. pmc Six blind men and the elephant--the many faces of heparan sulfate
    Ajit Varki
    Glycobiology Research and Training Center, Department of Medicine, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Proc Natl Acad Sci U S A 99:543-5. 2002
  84. pmc Explaining human uniqueness: genome interactions with environment, behaviour and culture
    Ajit Varki
    Center for Academic Research and Training in Anthropogeny, University of California, San Diego, La Jolla, California 92093, USA
    Nat Rev Genet 9:749-63. 2008
    ....
  85. ncbi request reprint Emerging opportunities and career paths for the young physician-scientist
    Ajit Varki
    Department of Medicine, Glycobiology Research and Training Center, University of California San Diego, La Jolla, California, USA
    Nat Med 8:437-9. 2002
  86. pmc Sialic acids in human health and disease
    Ajit Varki
    Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Trends Mol Med 14:351-60. 2008
    ..This review considers some examples of their established and newly emerging roles in aspects of human physiology and disease...
  87. pmc Trousseau's syndrome: multiple definitions and multiple mechanisms
    Ajit Varki
    University of California, San Diego, La Jolla CA 92093 0687, USA
    Blood 110:1723-9. 2007
    ....
  88. ncbi request reprint Comparing the human and chimpanzee genomes: searching for needles in a haystack
    Ajit Varki
    Glycobiology Research and Training Center, Departments of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA
    Genome Res 15:1746-58. 2005
    ..These two approaches will intersect at many levels and should be considered complementary. We also cite some known genetic differences between humans and great apes, realizing that these likely represent only the tip of the iceberg...
  89. ncbi request reprint Characterization of the acid stability of glycosidically linked neuraminic acid: use in detecting de-N-acetyl-gangliosides in human melanoma
    Justin L Sonnenburg
    Glycobiology Research and Training Center, Department of Medicine, University of California, San Diego, La Jolla, California 92093 0687, USA
    J Biol Chem 277:17502-10. 2002
    ..These advances allowed us to detect covalently bound Neu in lipid extracts of a human melanoma tumor, providing the first chemical proof for naturally occurring de-N-acetyl-gangliosides...
  90. pmc Discovery and characterization of sialic acid O-acetylation in group B Streptococcus
    Amanda L Lewis
    Division of Biological Sciences, Glycobiology Research and Training Center, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Proc Natl Acad Sci U S A 101:11123-8. 2004
    ..Thus, our discovery has important implications for GBS pathogenicity, immunogenicity, and vaccine design...
  91. ncbi request reprint Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective
    Takashi Angata
    Glycobiology Research and Training Center, Department of Medicine, University of California San Diego, La Jolla, California 92093 0687, USA
    Chem Rev 102:439-69. 2002
  92. ncbi request reprint Probing for masked and unmasked siglecs on cell surfaces
    Els C Brinkman-Van der Linden
    Departments of Medicine and Cellular Molecular Medicine, University of California San Diego, School of Medicine, La Jolla, California 92093, USA
    Methods Enzymol 363:113-20. 2003
  93. pmc Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution
    Hsun Hua Chou
    Glycobiology Research and Training Center, Department of Medicine, University of California at San Diego, La Jolla, CA 92093 0687, USA
    Proc Natl Acad Sci U S A 99:11736-41. 2002
    ..1-2.2 mya. In this regard, it is of interest that although Neu5Gc is the major sialic acid in most organs of the chimpanzee, its expression is selectively down-regulated in the brain, for as yet unknown reasons...
  94. ncbi request reprint Genomics. Thoughts on the future of great ape research
    Edwin H McConkey
    Science 309:1499-501. 2005
  95. ncbi request reprint The ethics of research on great apes
    Pascal Gagneux
    Conservation and Research for Endangered Species, Zoological Society of San Diego, San Diego, California, USA
    Nature 437:27-9. 2005
  96. ncbi request reprint Intra- and interspecific variation in primate gene expression patterns
    Wolfgang Enard
    Max Planck Institute for Evolutionary Anthropology, Inselstrasse 22, D 04103 Leipzig, Germany
    Science 296:340-3. 2002
    ..We identified species-specific gene expression patterns indicating that changes in protein and gene expression have been particularly pronounced in the human brain...
  97. ncbi request reprint Siglecs and their roles in the immune system
    Paul R Crocker
    Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, Dundee DD 15EH, UK
    Nat Rev Immunol 7:255-66. 2007
    ..Finally, we discuss the postulated functions of the recently discovered CD33-related Siglecs and consider the factors that seem to be driving their rapid evolution...
  98. ncbi request reprint Genomics. The chimpanzee genome--a bittersweet celebration
    Maynard V Olson
    University of Washington Genome Center, Departments of Medicine and Genome Sciences, Seattle, WA 98195, USA
    Science 305:191-2. 2004
  99. ncbi request reprint Heparin inhibits the flow adhesion of sickle red blood cells to P-selectin
    Neil M Matsui
    Department of Pediatrics, University of California San Francisco, San Francisco General Hospital, and the Northern California Comprehensive Sickle Cell Center, San Francisco 94110, USA
    Blood 100:3790-6. 2002
    ..A clinical trial to test this hypothesis is indicated...
  100. ncbi request reprint The uncertain future of research chimpanzees
    Ajit Varki
    Science 315:1493-4. 2007
  101. ncbi request reprint Sequencing the chimpanzee genome: insights into human evolution and disease
    Maynard V Olson
    University of Washington Genome Center, Department of Medicine, University of Washington, Seattle, Washington 98195, USA
    Nat Rev Genet 4:20-8. 2003
    ..Second, chimpanzee-human comparisons are likely to yield molecular insights into how new biological characteristics evolve--findings that might be relevant throughout the tree of life...