Imperial College London

DrMariaPanico

Faculty of Natural SciencesDepartment of Life Sciences

Laboratory Manager
 
 
 
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Contact

 

+44 (0)20 7594 5204m.panico

 
 
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Location

 

102Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

179 results found

Antonopoulos A, Broome S, Sharov V, Ziegenfuss C, Easton RL, Panico M, Morris HR, Haslam Set al., 2021, Site-specific characterisation of SARS-CoV-2 spike glycoprotein receptor binding domain, Glycobiology, Vol: 31, Pages: 181-187, ISSN: 0959-6658

The novel coronavirus SARS-CoV-2, the infective agent causing COVID-19, is having a global impact both in terms of human disease as well as socially and economically. Its heavily glycosylated spike glycoprotein is fundamental for the infection process, via its receptor binding domains interaction with the glycoprotein angiotensin converting enzyme 2 on human cell surfaces. We therefore utilized an integrated glycomic and glycoproteomic analytical strategy to characterise both N- and O- glycan site specific glycosylation within the receptor binding domain. We demonstrate the presence of complex type N-glycans with unusual fucosylated LacdiNAc at both sites N331 and N343 and a single site of O-glycosylation on T323.

Journal article

Mendoza M, Lu D, Ballesteros A, Blois SM, Abernathy K, Feng C, Dimitroff CJ, Zmuda J, Panico M, Dell A, Vasta GR, Haslam SM, Dveksler Get al., 2020, Glycan characterization of pregnancy-specific glycoprotein 1 and its identification as a novel Galectin-1 ligand, Glycobiology, Vol: 30, Pages: 895-909, ISSN: 0959-6658

Pregnancy-specific beta 1 glycoprotein (PSG1) is secreted from trophoblast cells of the human placenta in increasing concentrations as pregnancy progresses, becoming one of the most abundant proteins in maternal serum in the third trimester. PSG1 has seven potential N-linked glycosylation sites across its four domains. We carried out glycomic and glycoproteomic studies to characterize the glycan composition of PSG1 purified from serum of pregnant women and identified the presence of complex N-glycans containing poly LacNAc epitopes with α2,3 sialyation at four sites. Using different techniques, we explored whether PSG1 can bind to galectin-1 (Gal-1) as these two proteins were previously shown to participate in processes required for a successful pregnancy. We confirmed that PSG1 binds to Gal-1 in a carbohydrate-dependent manner with an affinity of the interaction of 0.13 μM. In addition, we determined that out of the three N-glycosylation-carrying domains, only the N and A2 domains of recombinant PSG1 interact with Gal-1. Lastly, we observed that the interaction between PSG1 and Gal-1 protects this lectin from oxidative inactivation and that PSG1 competes the ability of Gal-1 to bind to some but not all of its glycoprotein ligands.

Journal article

Ibeto L, Antonopoulos A, Grassi P, Pang P-C, Panico M, Bobdiwala S, Al-Memar M, Davis P, Davis M, Norman Taylor J, Almeida P, Johnson MR, Harvey R, Bourne T, Seckl M, Clark G, Haslam SM, Dell Aet al., 2020, Insights into the hyperglycosylation of human chorionic gonadotropin revealed by glycomics analysis, PLoS One, Vol: 15, ISSN: 1932-6203

Human chorionic gonadotropin (hCG) is a glycoprotein hormone that is essential for the maintenance of pregnancy. Glycosylation of hCG is known to be essential for its biological activity. "Hyperglycosylated" variants secreted during early pregnancy have been proposed to be involved in initial implantation of the embryo and as a potential diagnostic marker for gestational diseases. However, what constitutes "hyperglycosylation" is not yet fully understood. In this study, we perform comparative N-glycomic analysis of hCG expressed in the same individuals during early and late pregnancy to help provide new insights into hCG function, reveal new targets for diagnostics and clarify the identity of hyperglycosylated hCG. hCG was isolated in urine collected from women at 7 weeks and 20 weeks' gestation. hCG was also isolated in urine from women diagnosed with gestational trophoblastic disease (GTD). We used glycomics methodologies including matrix assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass spectrometry (MS) and MS/MS methods to characterise the N-glycans associated with hCG purified from the individual samples. The structures identified on the early pregnancy (EP-hCG) and late pregnancy (LP-hCG) samples corresponded to mono-, bi-, tri-, and tetra-antennary N-glycans. A novel finding was the presence of substantial amounts of bisected type N-glycans in pregnancy hCG samples, which were present at much lower levels in GTD samples. A second novel observation was the presence of abundant LewisX antigens on the bisected N-glycans. GTD-hCG had fewer glycoforms which constituted a subset of those found in normal pregnancy. When compared to EP-hCG, GTD-hCG samples had decreased signals for tri- and tetra-antennary N-glycans. In terms of terminal epitopes, GTD-hCG had increased signals for sialylated structures, while LewisX antigens were of very minor abundance. hCG carries the same N-glycans throughout pregnancy but in different propo

Journal article

Hunt R, Hettiarachchi G, Katneni U, Hernandez N, Holcomb D, Kames J, Alnifaidy R, Lin B, Hamasaki-Katagiri N, Wesley A, Kafri T, Morris C, Bouche L, Panico M, Schiller T, Ibla J, Bar H, Ismail A, Morris H, Komar A, Kimchi-Sarfaty Cet al., 2019, A single synonymous variant (c.354G > A [p.P118P]) in ADAMTS13 confers enhanced specific activity, International Journal of Molecular Sciences, Vol: 20, Pages: 1-18, ISSN: 1422-0067

Synonymous variants within coding regions may influence protein expression and function. We have previously reported increased protein expression levels ex vivo (~120% in comparison to wild-type) from a synonymous polymorphism variant, c.354G>A [p.P118P], of the ADAMTS13 gene, encoding a plasma protease responsible for von Willebrand Factor (VWF) degradation. In the current study, we investigated the potential mechanism(s) behind the increased protein expression levels from this variant and its effect on ADAMTS13 physico-chemical properties. Cell-free assays showed enhanced translation of the c.354G>A variant and the analysis of codon usage characteristics suggested that introduction of the frequently used codon/codon pair(s) may have been potentially responsible for this effect. Limited proteolysis, however, showed no substantial influence of altered translation on protein conformation. Analysis of post-translational modifications also showed no notable differences but identified three previously unreported glycosylation markers. Despite these similarities, p.P118P variant unexpectedly showed higher specific activity. Structural analysis using modeled interactions indicated that subtle conformational changes arising from altered translation kinetics could affect interactions between an exosite of ADAMTS13 and VWF resulting in altered specific activity. This report highlights how a single synonymous nucleotide variation can impact cellular expression and specific activity in the absence of measurable impact on protein structure.

Journal article

Richards E, Bouché L, Panico M, Arbeloa A, Vinogradov E, Morris H, Wren B, Logan SM, Dell A, Fairweather NFet al., 2018, The S-layer protein of a Clostridium difficile SLCT-11 strain displays a complex glycan required for normal cell growth and morphology., Journal of Biological Chemistry, Vol: 293, Pages: 18123-18137, ISSN: 0021-9258

Clostridium difficile is a bacterial pathogen that causes major health challenges worldwide. It has a well-characterized surface (S)-layer, a para-crystalline proteinaceous layer surrounding the cell wall. In many bacterial and archaeal species, the S-layer is glycosylated, but no such modifications have been demonstrated in C. difficile. Here, we show that a C. difficilestrain of S-layer cassette type 11, Ox247, has a complex glycan attached via an O-linkage to Thr-38 of the S-layer low-molecular-weight subunit. Using mass spectrometry and NMR, we fully characterized this glycan. We present evidence that it is composed of three domains: (i) a core peptide-linked tetrasaccharide with the sequence -4-α-Rha-3-α-Rha-3-α-Rha-3-β-Gal-peptide, (ii) a repeating pentasaccharide with the sequence -4-β-Rha-4-α-Glc-3-β-Rha-4-(α-Rib-3-)β-Rha-, and (iii) a non-reducing end-terminal 2,3 cyclophosphoryl-rhamnose attached to a ribose-branched sub-terminal rhamnose residue. The Ox247 genome contains a 24 kb locus containing genes for synthesis and protein attachment of this glycan. Mutations in genes within this locus altered or completely abrogated formation of this glycan, and their phenotypes suggested that this S-layer modification may affect sporulation, cell length, and biofilm formation of C. difficile. In summary, our findings indicate that the S-layer protein of SLCT-11 strains displays a complex glycan and suggest that this glycan is required for C. difficilesporulation and control of cell shape, a discovery with implications for the development of antimicrobials targeting the S-layer.

Journal article

Wendel U, Persson N, Risinger C, Mirgorodskaya E, Sihlbom C, Bengtsson E, Nodin B, Danielsson L, Welinder C, Panico M, Dell A, Haslam S, Fredrikson GN, Jansson B, Blixt Oet al., 2017, Site-specific detection of advanced glycation endproducts with newly developed single-chain variable fragment antibodies, Annual Meeting of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 1245-1246, ISSN: 0959-6658

Conference paper

Bouché L, Panico M, Hitchen P, Binet D, Sastre F, Faulds-Pain A, Valiente E, Vinogradov E, Aubry A, Fulton K, Twine S, Logan SM, Wren BW, Dell A, Morris HRet al., 2016, The Type B flagellin of hypervirulent Clostridium difficile is modified with novel sulphonated Peptidylamido-glycans, Journal of Biological Chemistry, Vol: 291, Pages: 25439-25449, ISSN: 1083-351X

Glycosylation of flagellins is a well recognized property of many bacterial species. In this study we describe the structural characterization of novel flagellar glycans from a number of hypervirulent strains of C. difficile. We used mass spectrometry (nano LC- MS and MS/MS analysis) to identify a number of putative glycopeptides which carried a variety of glycoform substitutions each of which was linked through an initial HexNAc residue to Ser or Thr. Detailed analysis of a LLDGSSTEIR glycopeptide released by tryptic digestion, which carried two variant structures, revealed that the glycopeptide contained, in addition to carbohydrate moieties, a novel structural entity. A variety of Electrospray-MS strategies using Q-TOF technology were used to define this entity, including positive- and negative-ion collisionally activated decomposition (CAD) MS/MS which produced unique fragmentation patterns, and high resolution accurate mass measurement to allow derivation of atomic compositions, leading to the suggestion of a Taurine-containing peptidylamido-glycan structure. Finally NMR analysis of flagellin glycopeptides provided complementary information. The glycan portion of the modification was assigned as α-Fuc3N-(1→3)-α-Rha-(1→2)-α-Rha3OMe-(1→3)-β-GlcNAc-(1→)Ser and the novel capping moiety was shown to be comprised of Taurine, Alanine, and Glycine. This is the first report of a novel O-linked sulphonated peptidylamido-glycan moiety decorating a flagellin protein.

Journal article

Valiente E, Bouche L, Hitchen P, Faulds-Pain A, Songane M, Dawson LF, Donahue E, Stabler RA, Panico M, Morris HR, Bajaj-Elliott M, Logan SM, Dell A, Wren BWet al., 2016, Role of glycosyltransferases modifying type B flagellin of emerging hypervirulent Clostridium difficile lineages and their impact on motility and biofilm formation, Journal of Biological Chemistry, Vol: 291, Pages: 25450-25461, ISSN: 1083-351X

Clostridium difficile is the principal cause of nosocomial infectious diarrhea worldwide. The pathogen modifies its flagellin with either a type A or type B O-linked glycosylation system, which has a contributory role in pathogenesis. We study the functional role of glycosyltransferases modifying type B flagellin in the 023 and 027 hypervirulent C. difficile lineages by mutagenesis of five putative glycosyltransferases and biosynthetic genes. We reveal their roles in the biosynthesis of the flagellin glycan chain and demonstrate that flagellar post-translational modification affects motility and adhesion-related bacterial properties of these strains. We show that the glycosyltransferases 1 and 2 (GT1 and GT2) are responsible for the sequential addition of a GlcNAc and two rhamnoses, respectively, and that GT3 is associated with the incorporation of a novel sulfonated peptidyl-amido sugar moiety whose structure is reported in our accompanying paper (Bouché, L., Panico, M., Hitchen, P., Binet, D., Sastre, F., Faulds-Pain, A., Valiente, E., Vinogradov, E., Aubry, A., Fulton, K., Twine, S., Logan, S. M., Wren, B. W., Dell, A., and Morris, H. R. (2016) J. Biol. Chem. 291, 25439–25449). GT2 is also responsible for methylation of the rhamnoses. Whereas type B modification is not required for flagellar assembly, some mutations that result in truncation or abolition of the glycan reduce bacterial motility and promote autoaggregation and biofilm formation. The complete lack of flagellin modification also significantly reduces adhesion of C. difficile to Caco-2 intestinal epithelial cells but does not affect activation of human TLR5. Our study advances our understanding of the genes involved in flagellar glycosylation and their biological roles in emerging hypervirulent C. difficile strains.

Journal article

Panico M, Bouché L, Binet D, O'Connor MJ, Rahman D, Pang PC, Canis K, North SJ, Desrosiers RC, Chertova E, Keele BF, Bess JW, Lifson JD, Haslam SM, Dell A, Morris HRet al., 2016, Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding, Scientific Reports, Vol: 6, Pages: 1-17, ISSN: 2045-2322

The surface envelope glycoprotein (SU) of Human immunodeficiency virus type 1 (HIV-1), gp120SU plays an essential role in virus binding to target CD4+ T-cells and is a major vaccine target. Gp120 has remarkably high levels of N-linked glycosylation and there is considerable evidence that this “glycan shield” can help protect the virus from antibody-mediated neutralization. In recent years, however, it has become clear that gp120 glycosylation can also be included in the targets of recognition by some of the most potent broadly neutralizing antibodies. Knowing the site-specific glycosylation of gp120 can facilitate the rational design of glycopeptide antigens for HIV vaccine development. While most prior studies have focused on glycan analysis of recombinant forms of gp120, here we report the first systematic glycosylation site analysis of gp120 derived from virions produced by infected T lymphoid cells and show that a single site is exclusively substituted with complex glycans. These results should help guide the design of vaccine immunogens.

Journal article

Wu G, Hitchen PG, Panico M, North SJ, Barbouche MR, Binet D, Morris HR, Dell A, Haslam SMet al., 2015, Glycoproteomic studies of IgE from a novel hyper IgE syndrome linked to PGM3 mutation, Glycoconjugate Journal, Vol: 33, Pages: 447-456, ISSN: 1573-4986

Glycans serve as important regulators of antibody activities and half-lives. IgE is the most heavily glycosylated antibody, but in comparison to other antibodies little is known about its glycan structure function relationships. We therefore describe the site specific IgE glycosylation from a patient with a novel hyper IgE syndrome linked to mutations in PGM3, which is an enzyme involved in synthesizing UDP-GlcNAc, a sugar donor widely required for glycosylation. A two-step method was developed to prepare two IgE samples from less than 1 mL of serum collected from a patient with PGM3 mutation and a patient with atopic dermatitis as a control subject. Then, a glycoproteomic strategy was used to study the site-specific glycosylation. No glycosylation was found at Asn264, whilst high mannose glycans were only detected at Asn275, tri-antennary glycans were exclusively observed at Asn99 and Asn252, and non-fucosylated complex glycans were detected at Asn99. The results showed similar glycosylation profiles between the two IgE samples. These observations, together with previous knowledge of IgE glycosylation, imply that IgE glycosylation is similarly regulated among healthy control, allergy and PGM3 related hyper IgE syndrome.

Journal article

Dell A, Morris HR, Panico M, Haslam SM, Pang P-C, Bouche L, Binet D, O'Connor M-J, Stansell E, Chertova E, Bess J, Lifson JD, Desrosiers RCet al., 2015, N- and O-glycosylation of gp120 isolated from HIV virions, Glycobiology: accelerating impact across the biomedical sciences, Publisher: Oxford University Press (OUP), Pages: 1230-1230, ISSN: 1460-2423

Conference paper

Stansell A, 2015, Gp120 on HIV-1 Virions Lacks O-Linked Carbohydrate, PLOS ONE, Vol: 10, Pages: 1-15

As HIV-1-encoded envelope protein traverses the secretory pathway, it may be modified with N- and O-linked carbohydrate. When the gp120s of HIV-1 NL4-3, HIV-1 YU2, HIV-1 Bal, HIV-1 JRFL, and HIV-1 JRCSF were expressed as secreted proteins, the threonine at consensus position 499 was found to be O-glycosylated. For SIVmac239, the corresponding threonine was also glycosylated when gp120 was recombinantly expressed. Similarly-positioned, highly-conserved threonines in the influenza A virus H1N1 HA1 and H5N1 HA1 envelope proteins were also found to carry O-glycans when expressed as secreted proteins. In all cases, the threonines were modified predominantly with disialylated core 1 glycans, together with related core 1 and core 2 structures. Secreted HIV-1 gp140 was modified to a lesser extent with mainly monosialylated core 1 O-glycans, suggesting that the ectodomain of the gp41 transmembrane component may limit the accessibility of Thr499 to glycosyltransferases. In striking contrast to these findings, gp120 on purified virions of HIV-1 Bal and SIV CP-MAC lacked any detectable O-glycosylation of the C-terminal threonine. Our results indicate the absence of O-linked carbohydrates on Thr499 as it exists on the surface of virions and suggest caution in the interpretation of analyses of post-translational modifications that utilize recombinant forms of envelope protein.

Journal article

Haslam S, Panico M, Morris H, Dell Aet al., 2013, Glycomics and glycoproteomics-providing new biological insights, Annual Conference of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 1330-1330, ISSN: 0959-6658

Conference paper

Ishihara M, Bubendorfer S, Dohlich K, Heiss C, Vogel J, Sastre F, Panico M, Hitchen P, Dell A, Thormann K, Azadi Pet al., 2013, Analyzing the modification of the <i>Shewanella oneidensis</i> MR-1 flagellar filament, Annual Conference of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 1352-1352, ISSN: 0959-6658

Conference paper

Bubendorfer S, Ishihara M, Dohlich K, Heiss C, Vogel J, Sastre F, Panico M, Hitchen P, Dell A, Azadi P, Thormann KMet al., 2013, Analyzing the Modification of the <i>Shewanella oneidensis</i> MR-1 Flagellar Filament, PLOS ONE, Vol: 8, ISSN: 1932-6203

Journal article

Meyer BH, Peyfoon E, Dietrich C, Hitchen P, Panico M, Morris HR, Dell A, Albers S-Vet al., 2013, Agl16, a Thermophilic Glycosyltransferase Mediating the Last Step of <i>N</i>-Glycan Biosynthesis in the Thermoacidophilic Crenarchaeon <i>Sulfolobus acidocaldarius</i>, JOURNAL OF BACTERIOLOGY, Vol: 195, Pages: 2177-2186, ISSN: 0021-9193

Journal article

Canis K, McKinnon TAJ, Nowak A, Haslam SM, Panico M, Morris HR, Laffan MA, Dell Aet al., 2012, Mapping the N-glycome of human von Willebrand factor, BIOCHEMICAL JOURNAL, Vol: 447, Pages: 217-228, ISSN: 0264-6021

Journal article

Harrison R, Hitchen PG, Panico M, Morris HR, Mekhaiel D, Pleass RJ, Dell A, Hewitt JE, Haslam SMet al., 2012, Glycoproteomic characterization of recombinant mouse α-dystroglycan, GLYCOBIOLOGY, Vol: 22, Pages: 662-675, ISSN: 0959-6658

Journal article

Clark GF, Grassi P, Pang P, Panico M, Lafrenz D, Drobnis EZ, Baldwin MR, Morris HR, Haslam SM, Schedin-Weiss S, Sun W, Dell Aet al., 2012, Tumor Biomarker Glycoproteins in the Seminal Plasma of Healthy Human Males Are Endogenous Ligands for DC-SIGN, Molecular & Cellular Proteomics, Vol: 11

DC-SIGN is an immune C-type lectin that is expressed on both immature and mature dendritic cells associated with peripheral and lymphoid tissues in humans. It is a pattern recognition receptor that binds to several pathogens including HIV-1, Ebola virus, Mycobacterium tuberculosis, Candida albicans, Helicobacter pylori, and Schistosoma mansoni. Evidence is now mounting that DC-SIGN also recognizes endogenous glycoproteins, and that such interactions play a major role in maintaining immune homeostasis in humans and mice. Autoantigens (neoantigens) are produced for the first time in the human testes and other organs of the male urogenital tract under androgenic stimulus during puberty. Such antigens trigger autoimmune orchitis if the immune response is not tightly regulated within this system. Endogenous ligands for DC-SIGN could play a role in modulating such responses. Human seminal plasma glycoproteins express a high level of terminal Lewisx and Lewisy carbohydrate antigens. These epitopes react specifically with the lectin domains of DC-SIGN. However, because the expression of these sequences is necessary but not sufficient for interaction with DC-SIGN, this study was undertaken to determine if any seminal plasma glycoproteins are also endogenous ligands for DC-SIGN. Glycoproteins bearing terminal Lewisx and Lewisy sequences were initially isolated by lectin affinity chromatography. Protein sequencing established that three tumor biomarker glycoproteins (clusterin, galectin-3 binding glycoprotein, prostatic acid phosphatase) and protein C inhibitor were purified by using this affinity method. The binding of DC-SIGN to these seminal plasma glycoproteins was demonstrated in both Western blot and immunoprecipitation studies. These findings have confirmed that human seminal plasma contains endogenous glycoprotein ligands for DC-SIGN that could play a role in maintaining immune homeostasis both in the male urogenital tract and the vagina after coitus.

Journal article

Meyer BH, Zolghadr B, Peyfoon E, Pabst M, Panico M, Morris HR, Haslam SM, Messner P, Schaeffer C, Dell A, Albers S-Vet al., 2011, Sulfoquinovose synthase - an important enzyme in the N-glycosylation pathway of Sulfolobus acidocaldarius, MOLECULAR MICROBIOLOGY, Vol: 82, Pages: 1150-1163, ISSN: 0950-382X

Journal article

Stansell E, Canis K, Huang I-C, Panico M, Morris H, Haslam S, Farzan M, Dell A, Desrosiers Ret al., 2011, O-Glycosylation of the Envelope Glycoprotein of the Human Immunodeficiency Virus, Annual Conference of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 1454-1454, ISSN: 0959-6658

Conference paper

Pang P, Chiu PCN, Lee C, Chang L, Panico M, Morris HR, Haslam SM, Khoo K, Clark GF, Yeung WSB, Dell Aet al., 2011, Human Sperm Binding Is Mediated by the Sialyl-Lewisx Oligosaccharide on the Zona Pellucida, Science, Vol: 333, Pages: 1761-1764

Human fertilization begins when spermatozoa bind to the extracellular matrix coating of the oocyte, known as the zona pellucida (ZP). One spermatozoan then penetrates this matrix and fuses with the egg cell, generating a zygote. Although carbohydrate sequences on the ZP have been implicated in sperm binding, the nature of the ligand was unknown. Here, ultrasensitive mass spectrometric analyses revealed that the sialyl-Lewisx sequence [NeuAcα2-3Galβ1-4(Fucα1-3)GlcNAc], a well-known selectin ligand, is the most abundant terminal sequence on the N- and O-glycans of human ZP. Sperm-ZP binding was largely inhibited by glycoconjugates terminated with sialyl-Lewisx sequences or by antibodies directed against this sequence. Thus, the sialyl-Lewisx sequence represents the major carbohydrate ligand for human sperm-egg binding.

Journal article

Ahnstrom J, Andersson HM, Canis K, Norstrom E, Yu Y, Dahlback B, Panico M, Morris HR, Crawley JTB, Lane DAet al., 2011, Activated protein S cofactor function of protein S: a novel function for a γ-carboxyglutamic acid residue, Publisher: WILEY-BLACKWELL, Pages: 14-14, ISSN: 1538-7933

Conference paper

Ahnstroem J, Andersson HM, Canis K, Norstrom E, Yu Y, Dahlback B, Panico M, Morris HR, Crawley JTB, Lane DAet al., 2011, Activated protein C cofactor function of protein S: a novel role for a γ-carboxyglutamic acid residue, BLOOD, Vol: 117, Pages: 6685-6693, ISSN: 0006-4971

Journal article

Lee C, Chiu PCN, Pang P, Chu IK, Lee K, Koistinen R, Koistinen H, Seppälä M, Morris HR, Tissot B, Panico M, Dell A, Yeung WSBet al., 2011, Glycosylation Failure Extends to Glycoproteins in Gestational Diabetes Mellitus: Evidence From Reduced α2-6 Sialylation and Impaired Immunomodulatory Activities of Pregnancy-Related Glycodelin-A, Diabetes, Vol: 60, Pages: 909-917

OBJECTIVE Gestational diabetes mellitus (GDM) is a common metabolic disorder of pregnancy. Patients with GDM are at risk for high fetal mortality and gestational complications associated with reduced immune tolerance and abnormal carbohydrate metabolism. Glycodelin-A (GdA) is an abundant decidual glycoprotein with glycosylation-dependent immunomodulatory activities. We hypothesized that aberrant carbohydrate metabolism in GDM was associated with changes in glycosylation of GdA, leading to defective immunomodulatory activities.RESEARCH DESIGN AND METHODS GdA in the amniotic fluid from women with normal (NGdA) and GDM (DGdA) pregnancies was purified by affinity chromatography. Structural analysis of protein glycosylation was preformed by lectin-binding assay and mass spectrometry. Cytotoxicity, cell death, cytokine secretion, and GdA binding of the GdA-treated lymphocytes and natural killer (NK) cells were determined. The sialidase activity in the placental tissue from normal and GDM patients was measured.RESULTS GDM affected the glycosylation but not the protein core of GdA. Specifically, DGdA had a lower abundance of α2-6–sialylated and high-mannose glycans and a higher abundance of glycans with Sda (NeuAcα2-3[GalNAcβ1-4]Gal) epitopes compared with NGdA. DGdA had reduced immuosuppressive activities in terms of cytotoxicity on lymphocytes, inhibitory activities on interleukin (IL)-2 secretion by lymphocytes, stimulatory activities on IL-6 secretion by NK cells, and binding to these cells. Desialylation abolished the immunomodulation and binding of NGdA. Placental sialidase activity was increased in GDM patients, which may account for the reduced sialic acid content of DGdA.CONCLUSIONS Taken together, this study provides the first direct evidence for altered enzymatic glycosylation and impaired bioactivity of GdA in GDM patients.

Journal article

Ismail MN, Stone EL, Panico M, Lee SH, Luu Y, Ramirez K, Ho SB, Fukuda M, Marth JD, Haslam SM, Dell Aet al., 2011, High-sensitivity <i>O</i>-glycomic analysis of mice deficient in core 2 β1,6-<i>N</i>-acetylglucosaminyltransferases, GLYCOBIOLOGY, Vol: 21, Pages: 82-98, ISSN: 0959-6658

Journal article

Morris C, Banks DJ, Gaweda L, Scott S, Zhu XX, Panico M, Georgiou P, Toumazou Cet al., 2011, A Robust Microfluidic <i>in vitro</i> Cell Perifusion System, 2011 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC), Pages: 8412-8415, ISSN: 1557-170X

Journal article

Clark G, Pang P-C, Grassi P, Panico M, Lafrenz D, Drobnis E, Baldwin M, Morris H, Dell Aet al., 2010, Tumor Biomarker Glycoproteins Present in the Seminal Plasma of Healthy Human Males Are Novel Endogenous Ligands for DC-Sign, Annual Conference of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 1522-1522, ISSN: 0959-6658

Conference paper

Harris EN, Parry S, Sutton-Smith M, Pandey MS, Panico M, Morris HR, Haslam SM, Dell A, Weigel PHet al., 2010, <i>N-</i>Glycans on the link domain of human HARE/Stabilin-2 are needed for hyaluronan binding to purified ecto-domain, but not for cellular endocytosis of hyaluronan, GLYCOBIOLOGY, Vol: 20, Pages: 991-1001, ISSN: 0959-6658

Journal article

Garner OB, Aguilar HC, Fulcher JA, Levroney EL, Harrison R, Wright L, Robinson LR, Aspericueta V, Panico M, Haslam SM, Morris HR, Dell A, Lee B, Baum LGet al., 2010, Endothelial Galectin-1 Binds to Specific Glycans on Nipah Virus Fusion Protein and Inhibits Maturation, Mobility, and Function to Block Syncytia Formation, PLOS PATHOGENS, Vol: 6, ISSN: 1553-7366

Journal article

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