Research Topics
Genomes and GenesSpecies | Ajit P VarkiSummaryAffiliation: University of California Country: USA Publications
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Publications
Factors controlling the glycosylation potential of the Golgi apparatusA Varki
Glycobiology Program, UCSD, La Jolla, USA
Trends Cell Biol 8:34-40. 1998..Old and new approaches towards elucidating the organization of glycosylation machinery in the Golgi are also considered...- P-selectin, carcinoma metastasis and heparin: novel mechanistic connections with therapeutic implicationsA Varki
Departments of Medicine and Pathology, Cancer Center and Glycobiology Research and Training Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0687, USA
Braz J Med Biol Res 34:711-7. 2001..We therefore suggest that heparin use in cancer be re-explored, specifically during the time interval between initial visualization of a primary tumor until just after definitive surgical removal... - N-glycolylneuraminic acid deficiency in humansA Varki
Glycobiology Research and Training Center and Department of Medicine, University of California, San Diego, La Jolla, CA 92093 0687, USA
Biochimie 83:615-22. 2001..This review provides an update on this matter, and considers a variety of other old and new questions that arise from it... - Six blind men and the elephant--the many faces of heparan sulfateAjit 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 - Emerging opportunities and career paths for the young physician-scientistAjit Varki
Department of Medicine, Glycobiology Research and Training Center, University of California San Diego, La Jolla, California, USA
Nat Med 8:437-9. 2002 - Human-specific regulation of alpha 2-6-linked sialic acidsPascal 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.... - Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasisLubor 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... - Differential metastasis inhibition by clinically relevant levels of heparins--correlation with selectin inhibition, not antithrombotic activityJennifer 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..Caution is also raised about the current preference for smaller heparins. Despite equivalent anticoagulation, hitherto unsuspected benefits of selectin inhibition in various clinical circumstances may be unwittingly discarded... - System-wide genomic and biochemical comparisons of sialic acid biology among primates and rodents: Evidence for two modes of rapid evolutionTasha 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.... - Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomasMark 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... - Human-specific expression of Siglec-6 in the placentaEls 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... - Large-scale sequencing of the CD33-related Siglec gene cluster in five mammalian species reveals rapid evolution by multiple mechanismsTakashi 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.... - Colloquium paper: uniquely human evolution of sialic acid genetics and biologyAjit 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.... - Nothing in glycobiology makes sense, except in the light of evolutionAjit 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... - Cell surface sialic acids do not affect primary CD22 interactions with CD45 and surface IgM nor the rate of constitutive CD22 endocytosisMai 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... - Mechanism of uptake and incorporation of the non-human sialic acid N-glycolylneuraminic acid into human cellsMuriel 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... - Trousseau's syndrome: multiple definitions and multiple mechanismsAjit Varki
University of California, San Diego, La Jolla CA 92093 0687, USA
Blood 110:1723-9. 2007.... - Siglecs--the major subfamily of I-type lectinsAjit 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... - Evolution of human-chimpanzee differences in malaria susceptibility: relationship to human genetic loss of N-glycolylneuraminic acidMaria 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... - Glycan-based interactions involving vertebrate sialic-acid-recognizing proteinsAjit 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... - Comparing the human and chimpanzee genomes: searching for needles in a haystackAjit 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... - 9-O-acetylation of exogenously added ganglioside GD3. The GD3 molecule induces its own O-acetylation machineryHelen 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.... - A uniquely human consequence of domain-specific functional adaptation in a sialic acid-binding receptorJustin 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... - Diversity in cell surface sialic acid presentations: implications for biology and diseaseNissi 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... - Heparin inhibition of selectin-mediated interactions during the hematogenous phase of carcinoma metastasis: rationale for clinical studies in humansNissi 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... - Symbol nomenclature for glycan representationAjit 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... - 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 microgliaTakashi 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.... - Loss of Siglec expression on T lymphocytes during human evolutionDzung 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.... - Explaining human uniqueness: genome interactions with environment, behaviour and cultureAjit 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.... - Multiple changes in sialic acid biology during human evolutionAjit 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... - Sialic acids in human health and diseaseAjit 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... - Biomedical differences between human and nonhuman hominids: potential roles for uniquely human aspects of sialic acid biologyNissi 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... - The sialome--far more than the sum of its partsMiriam 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... - Heparin attenuates metastasis mainly due to inhibition of P- and L-selectin, but non-anticoagulant heparins can have additional effectsJennifer 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... - alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivoMaria 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... - Discovery and characterization of sialic acid O-acetylation in group B StreptococcusAmanda 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... - Innovations in host and microbial sialic acid biosynthesis revealed by phylogenomic prediction of nonulosonic acid structureAmanda 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... - Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune responseAaron 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... - Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5Aaron 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... - Effects of sialic acid substitutions on recognition by Sambucus nigra agglutinin and Maackia amurensis hemagglutininEls 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 - Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspectiveTakashi 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 - A human-specific gene in microgliaToshiyuki 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... - CD33/Siglec-3 binding specificity, expression pattern, and consequences of gene deletion in miceEls 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.... - Genetically altered mice with different sialyltransferase deficiencies show tissue-specific alterations in sialylation and sialic acid 9-O-acetylationLaura 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... - Human uptake and incorporation of an immunogenic nonhuman dietary sialic acidPam 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... - Probing for masked and unmasked siglecs on cell surfacesEls 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 - Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2Virginia D Winn
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USA
Endocrinology 150:452-62. 2009..The functional significance of these novel observations may provide new insights into the pathogenesis of PE, and assaying the circulating levels of these proteins could have clinical utility for predicting and/or diagnosing PE... - Relative over-reactivity of human versus chimpanzee lymphocytes: implications for the human diseases associated with immune activationPaula 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... - The ethics of research on great apesPascal Gagneux
Conservation and Research for Endangered Species, Zoological Society of San Diego, San Diego, California, USA
Nature 437:27-9. 2005 - Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteinsDarius 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... - Group B streptococcal capsular sialic acids interact with siglecs (immunoglobulin-like lectins) on human leukocytesAaron 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... - Sequencing the chimpanzee genome: insights into human evolution and diseaseMaynard 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... - ABO blood group glycans modulate sialic acid recognition on erythrocytesMiriam 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... - Myeloid precursors and acute myeloid leukemia cells express multiple CD33-related SiglecsDzung H Nguyen
Glycobiology Research and Training Center, University of California, San Diego, La Jolla, USA
Exp Hematol 34:728-35. 2006..CONCLUSIONS: Multiple CD33rSiglecs are expressed on normal and malignant myelomonoyctic cells. Targeting these Siglecs, possibly in combinations, could improve anti-CD33 antibody therapy or be used as an alternative to anti-CD33... - Advances in the biology and chemistry of sialic acidsXi Chen
Department of Chemistry, University of California, Davis, California 95616, USA
ACS Chem Biol 5:163-76. 2010..Research efforts not only will lead to a better understanding of the biological and pathological importance of sialic acids and their diversity but also could lead to the development of therapeutics... - Characterization of the acid stability of glycosidically linked neuraminic acid: use in detecting de-N-acetyl-gangliosides in human melanomaJustin 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... - Generation of mice deficient for macrophage galactose- and N-acetylgalactosamine-specific lectin: limited role in lymphoid and erythroid homeostasis and evidence for multiple lectinsThandi 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... - Heparin's anti-inflammatory effects require glucosamine 6-O-sulfation and are mediated by blockade of L- and P-selectinsLianchun 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... - Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophilsMai 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.... - Effects of natural human antibodies against a nonhuman sialic acid that metabolically incorporates into activated and malignant immune cellsDzung 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... - Overview of glycoconjugate analysisAjit 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... - Recombinant influenza C hemagglutinin-esterase as a probe for sialic acid 9-O-acetylationLaura 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 - NeuA sialic acid O-acetylesterase activity modulates O-acetylation of capsular polysaccharide in group B StreptococcusAmanda 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.... - 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 - Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolutionHsun 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... - 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... - Blasts from the pastPaul A Insel
J Clin Invest 114:1017-33. 2004....