carolyn bertozzi biography
This work provides a method to study the biosynthesis of fucosylated glycans in vivo. Carbohydrate biosynthetic pathways are often amenable to interception with synthetic unnatural substrates. In addition to carrying out a pivotal role in parasite persistence/replication within the infected mammal, the trans-sialidase is shed into the bloodstream and induces alterations in the host immune system by modifying the sialylation of the immune cells. Douglas, E. S., Chandra, R. A., Bertozzi, C. R., Mathies, R. A., Francis, M. B. Metabolic labeling of glycans with azido sugars and subsequent glycan-profiling and visualization via Staudinger ligation, Synthetic glycobiology: exploits in the Golgi compartment, Using phage display to select antibodies recognizing post-translational modifications independently of sequence context. and Kirk Schanze and Lee, {T. Randall} and Lutkenhaus, {Jodie L.} and David Kaplan and Christopher Jones and Carolyn Bertozzi and Laura Kiessling and Mulcahy, {Mary Beth} and Lindsley, {Craig W.} and Finn, {M. G.} and Blum, {Joel D.} and Prashant Kamat and View details for DOI 10.1016/j.cell.2006.08.017, View details for Web of Science ID 000240675000013. Heineken Prize for Biochemistry and Biophysics (2022); Wolf Prize (2022); AAAS Lifetime Mentor Award (2022); Presidents Innovator Award, Society for Glycobiology (2020); Nagoya Medal (2020); The Chemistry of the Future Solvay Prize (2020); NAS John J. Carty Award (2020); Glenn T. Seaborg Medal, UCLA (2020); F.A. Palmitoylation is a widespread, reversible lipid modification that has been implicated in regulating a variety of cellular processes. Leiden (2005); Iota Sigma Pi Agnes Fay Morgan Research Award (2004); Elected member of the American Academy of Arts and Sciences (2003); Irving Sigal Young Investigator Award of the Protein Society (2002); Fellow of the American Association for the Advancement of Science (2002); Donald Sterling Noyce Prize for Excellence in Undergraduate Teaching (2001); UC Berkeley Distinguished Teaching Award (2001); ACS Award in Pure Chemistry (2001); Merck Academic Development Program Award (2000); UC Berkeley Department of Chemistry Teaching Award (2000); Presidential Early Career Award in Science and Engineering (PECASE) (2000); MacArthur Foundation Award (1999); Camille Dreyfus Teacher-Scholar Award (1999); Arthur C. Cope Scholar Award (ACS) (1999); Joel H. Hildebrand Chair in Chemistry (1998-2000); Beckman Young Investigator Award (1998); Prytanean Faculty Award (1998); Glaxo Wellcome Scholar (1998); Research Corporation Research Innovation Award (1998); Office of Naval Research Young Investigator Award (1998); Horace S. Isbell Award in Carbohydrate Chemistry (ACS) (1997); Alfred P. Sloan Research Fellow (1997); Burroughs Wellcome New Investigator Award in Pharmacology (1997); Pew Scholars Award in the Biomedical Sciences (1996); Exxon Education Fund Young Investigator Award (1996); Camille and Henry Dreyfus New Faculty Award (1995); Bruce Mahan Teaching Award (1992); Outstanding Graduate Student Instructor Awards (1989, 1990); Thomas T. Hoopes Undergraduate Thesis Prize (1988); New England American Institute of Chemists Award (1988); Danforth Teaching Award (1987); Phi Beta Kappa (1987), Address:ChEM-H Building290 Jane Stanford Way, Room 235AStanford, CA 94305. Accordingly, treatment of cells with N-azidoacetylglucosamine results in the metabolic incorporation of the azido sugar into nuclear and cytoplasmic proteins. New additions to the bioorthogonal chemistry compendium can advance biological research by enabling multiplexed analysis of biomolecules in complex systems. Here we report the development of an HIV OF assay based on Antibody Detection by Agglutination-PCR (ADAP) technology. These screens identified CD22, a canonical Bcell receptor, as a negative regulator of phagocytosis that is upregulated on aged microglia. We report the 2.7 A resolution crystal structure of Pseudomonas aeruginosa APS reductase in the thiosulfonate intermediate form of the catalytic cycle and with substrate bound. This Account summarizes chemoselective approaches for assembling homogeneous glycoconjugates that attempt to reduce the barriers to their synthesis. This imaging approach should further our understanding of basic metabolic processes and pathological alterations in multiple disease models. Strong adhesion between the organic and inorganic materials was achieved for hydrogels functionalized with either carboxylate or hydroxy ligands. Upon changing to differentiation media, myotubes formed in the center of the patterned areas with an excellent degree of edge alignment. The active site residues of Rv3406 and AtsK are essentially superimposable, suggesting that the two sulfatases share the same catalytic mechanism. Numerous factors that influence cell-surface carbohydrate composition remain to be elucidated. Armstrong, J. I., Ge, X., Verdugo, D. E., Winans, K. A., Leary, J. Molecules terminated with Alexa Fluor 488 projected away from the lipid bilayer by 11 +/- 1 nm, consistent with entropy-dominated sampling of the membrane-proximal space. Incorporation of azide-functionalized amino acids into proteins in vivo provides opportunities for protein modification under native conditions and selective labeling of proteins in the intracellular environment. Mucin biology has been difficult to study at the molecular level, in part, because methods to manipulate and structurally characterize mucin domains are lacking. The results from our study strongly suggest a rapid equilibrium random sequential Bi-Bi mechanism for Stf0 with formation of a ternary complex intermediate. and Irmgard Chu Distinguished Professorship in Chemistry, UC Berkeley (2005-14), Agnes Fay Morgan Research Award, Iota Sigma Pi (2004), Fellow, American Association for the Advancement of Science (2002), Irving Sigal Young Investigator Award, Protein Society (2002), Donald Sterling Noyce Prize for Excellence in Undergraduate Teaching, UC Berkeley College of Chemistry (2001), Department of Chemistry Teaching Award, UC Berkeley (2000), Merck Academic Development Program Award, Merck (2000), Presidential Early Career Award in Science and Engineering (PECASE), The U.S. White House (2000), Camille Dreyfus Teacher-Scholar Award, Camille and Henry Dreyfus Foundation (1999), Beckman Young Investigator Award, Arnold and Mabel Beckman Foundation (1998), Glaxo Wellcome Scholar, Glaxo Wellcome (1998), Prytanean Faculty Award, Prytanean Women's Honor Society, UC Berkeley (1998), Research Innovation Award, Research Corporation (1998), Young Investigator Award, Office of Naval Research (1998), Horace S. Isbell Award in Carbohydrate Chemistry, American Chemical Society (1997), New Investigator Award in Pharmacology, Burroughs Wellcome (1997), Sloan Research Fellow, Alfred P. Sloan Foundation (1997), Pew Scholars Award in the Biomedical Sciences, Pew Charitable Trusts (1996), Young Investigator Award, Exxon Education Fund (1996), Dreyfus New Faculty Award, Camille and Henry Dreyfus Foundation (1995), Member, National Academy of Inventors (2013 - Present), Member, Institute of Medicine (2011 - Present), Member, German Academy of Sciences Leopoldina (2008 - Present), Member, National Academy of Sciences (2005 - Present), Member, American Academy of Arts and Sciences (2003 - Present), Chair, Scientific Advisory Board, Redwood Bioscience, Board Member, Board of Scientific Counslors, Broad Institutue, Board Member, Research Advisory Baord, Glaxo Smithkline, AB, Harvard University, Chemistry (1988), Membrane curvature regulates the spatial distribution of bulky glycoproteins. Rv3406 was identified based on its homology to the alkyl sulfatase AtsK from Pseudomonas putida. Stanford University biochemist Carolyn Bertozzi is a highly admired scientist, entrepreneur, and advocate for diversity, particularly for LGBTQ+ people. A., Mills, J. R., Roforth, M. M., Pittock, S. J., McKeon, A., Page, K., Wolf, W. A., Sanda, S., Speake, C., Greenbaum, C. J., Tsai, C. Bump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells. View details for Web of Science ID 000296036700058, View details for PubMedCentralID PMC3187659. Woo, C. M., Lund, P. J., Huang, A. C., Davis, M. M., Bertozzi, C. R., Pitteri, S. n. Imaging Mycobacterial Trehalose Glycolipids. Alternative assays have employed thin-layer chromatography, but this procedure is time-consuming and requires radioactive materials. Treatment of hESCs with Ac4-5SGlcNAc during induction limited protein O-GlcNAcylation and also caused a dramatic decrease in global levels of UDP-GlcNAc. [30] In 2015, Bertozzi moved to Stanford University to join the ChEM-H Institute. This challenging process made her dream of MS of material collected on the tissue paper blots revealed 67 GalNAz-labeled proteins, including intracellular proteins. Furthermore, we developed a biomemetic coating strategy to interface BNNTs with proteins and cells. Directed evolution was used to improve the activity of JamB, a membrane-bound bifunctional desaturase/acetylenase. The effort was enabled by a new high-fidelity pattern-searching and glycopeptide validation algorithm termed IsoStamp v2.0, as well as by novel stable isotope probes. Ganesan, L., Shieh, P., Bertozzi, C. R., Levental, I. Isotope-targeted glycoproteomics (IsoTaG) analysis of sialylated N- and O-glycopeptides on an Orbitrap Fusion Tribrid using azido and alkynyl sugars. Mycobacterial carbohydrate sulfotransferase Stf0 catalyzes the sulfuryl group transfer from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to trehalose. A., Quang, C. N., Bertozzi, C. R. A sulfated metabolite produced by stf3 negatively regulates the virulence of Mycobacterium tuberculosis. Rabuka, D., Hubbard, S. C., Laughlin, S. T., Argade, S. P., Bertozzi, C. R. Chemical technologies for probing glycans, A role for sulfation-desulfation in the uptake of bisphenol A into breast tumor cells. Palaniappan, K. K., Hangauer, M. J., Smith, T. J., Smart, B. P., Pitcher, A. Bowman, K. G., Hemmerich, S., Bhakta, S., SINGER, M. S., Bistrup, A., ROSEN, S. D., Bertozzi, C. R. Chemical approaches to glycobiology and emerging carbohydrate-based therapeutic agents, A strategy for the chemoselective synthesis of O-linked glycopeptides with native sugar-peptide linkages. The installation of sulfate groups on the carbohydrate residues of glycoproteins, glycolipids, and glycosaminoglycans is a critical posttranslational modification that occurs in all higher eukaryotes. Epithelial ovarian cancer (EOC) is a disease responsible for more deaths among women in the Western world than all other gynecologic malignancies. IsoTaG is therefore an effective platform for identification of intact glycopeptides labeled by alkynyl or azido sugars and will facilitate further studies of the glycoproteome. View details for Web of Science ID 000085902800059. This hypothesis reflects the known oligomeric states of the galectins themselves and their binding properties with multivalent ligands in vitro, but direct evidence of their ability to cross-link ligands on a cell surface is lacking. These cells were used as substrates to examine the effect of inhibiting PSA synthesis on the development of neurons derived from the chick dorsal root ganglion. Redundancy of related family members and embryonic lethality both complicate genetic methods for deconvoluting functions of glycosyltransferases. Grossman, H. L., Myers, W. R., Vreeland, V. J., Bruehl, R., Alper, M. D., Bertozzi, C. R., Clarke, J. Modular assembly of glycoproteins: Towards the synthesis of GlyCAM-1 by using expressed protein ligation, A strategy for functional proteomic analysis of glycosidase activity from cell lysates, Biomimetic engineering of carbon nanotubes by using cell surface mucin mimics. Cell surface lipooligosaccharides (LOS) of H. ducreyi are thought to play important biological roles in host infection. Oligosaccharides on proteins and lipids play central roles in human health and disease. The best reagent for this application was dependent upon the specific structure of the azide. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. ADAP detects zepto- to attomoles of antibodies in 2 L of sample with a dynamic range spanning 5-6 orders of magnitude. Zurich (2009); Harrison Howe Award (2009); W. H. Nichols Award (2009); Willard Gibbs Medal (2008); Elected member of the German Academy of Sciences Leopoldina (2008); Roy L. Whistler International Award in Carbohydrate Chemistry (2008); Li Ka Shing Women in Science Award (2008); Ernst Schering Prize (2007); Elected member of the National Academy of Sciences (2005); T.Z. Under these conditions, Nrf1 is inactive in regulating proteasome subunit gene expression in response to proteasome inhibition. In cells, GlcNAc6ST-1 exists as a dimer; two cysteine residues within the stem and transmembrane domain were found to be critical for dimerization. Sequestration of peptides derived from an Escherichia coli proteome, pulse labeled with the bio-orthogonal amino acid azidohomoalanine as substitute for methionine, allows identification of numerous newly synthesized proteins. We found that extension of the N-acyl chain to six, seven, or eight carbon atoms dramatically reduced utilization by the biosynthetic machinery. Thus, cell assembly can be highly controlled, enabling the design of microtissues with defined cell composition and stoichiometry. The study of glycan function is a major frontier in biology that could benefit from small molecules capable of perturbing carbohydrate structures on cells. Here, we report an assay for mycobacterial strain assignment based on genetically conserved mycobacterial sulfatases. Roe, B. We report herein the chemical synthesis and preliminary mechanistic investigation of diptericin, an 82 residue glycopeptide that contains regions similar to two different types of antibacterial peptides. Palaniappan, K. K., Pitcher, A. Protein glycosylation can have an enormous variety of biological consequences, reflecting the molecular diversity encoded in glycan structures. She is the 50th American Cancer Society -funded researcher and the first woman researcher funded by ACS to win the prestigious honor. Godula, K., Rabuka, D., Nam, K. T., Bertozzi, C. R. Metabolic Labeling of Sialic Acids in Living Animals with Alkynyl Sugars. Although theoretical predictions suggest that proteins follow these pathways as a result of fluctuations that create unstable dense-liquid states, microscopic studies indicate these states are long-lived. In this report, we screened FGEs from M. tuberculosis and S. coelicolor against synthetic peptide libraries and identified new substrate sequences that diverge from the canonical motif. and Kirk Schanze and Lee, {T. Randall} and Lutkenhaus, {Jodie L.} and David Kaplan and Christopher Jones and Carolyn Bertozzi and Laura Kiessling and Mulcahy, {Mary Beth} and Lindsley, {Craig W.} and Finn, {M. G.} and Blum, {Joel D.} and Prashant Kamat and Although the polysialyltransferase ST8Sia IV is expressed in both primary and secondary human lymphoid organs, its product, polysialic acid (polySia), has been largely overlooked by immunologists. We investigated how the major phosphatase CD45 is excluded from contact sites, using single-molecule tracking. The consequence is an impressive body of new knowledge and technology, amassed using a relatively small bioorthogonal reaction compendium. B., Bertozzi, C. R., Pitteri, S. J., Giaccia, A. J., Plevritis, S. K. Toward Point-of-Care Detection of Mycobacterium tuberculosis: A Brighter Solvatochromic Probe Detects Mycobacteria within Minutes. Chemical syntheses of uniform glycoproteins and polymeric glycoprotein mimics have facilitated the study of individual glycoconjugates in the absence of glycan microheterogeneity. The unsymmetrical (2'-, 3'-, 4'- and 6'-) monodeoxy analogs were synthesized by desymmetrization of alpha,alpha-trehalose and subsequent deoxygenation under radical conditions. View details for Web of Science ID 000301161600025, View details for PubMedCentralID PMC3306817. We find that emergence of this supermolecular architecture is the outcome of hierarchical processes; the proteins condense in solution to form 2-D crystals, which then stack parallel to one another to create isotropic bilayered assemblies. Antibodies are widely used biomarkers for the diagnosis of many diseases. Methods for targeting of small molecules to cellular proteins can allow imaging with fluorophores that are smaller, brighter, and more photostable than fluorescent proteins. Metabolic labeling of glycans with a bioorthogonal chemical reporter such as the azide enables their visualization in cells and organisms as well as the enrichment of specific glycoprotein types for proteomic analysis. The outlined procedure is well defined in cell culture and has been executed with over 15 cell lines. We propose a model in which Golgi enzyme localization and competition orchestrate the biosynthesis of L-selectin ligands. View details for DOI 10.1073/pnas.0601167103, View details for Web of Science ID 000239069400007, View details for PubMedCentralID PMC1502431. We seeded collagen-glycosaminoglycan meshes, a widely used tissue engineering scaffold material, with human IMR-90 fibroblasts and compared transcript levels with control cells grown on tissue culture polystyrene. Click chemistry and bio-orthogonal chemistry. We found that the fucose salvage pathway enzymes are expressed during zebrafish embryogenesis but that they process the azide-modified substrates inefficiently. The protective efficacy of the current Mycobacterium bovis bacille Calmette-Gurin (BCG) vaccine is highly variable. As a first step toward the design and fabrication of biomimetic bonelike composite materials, we have developed a template-driven nucleation and mineral growth process for the high-affinity integration of hydroxyapatite with a poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel scaffold. Cell surface carbohydrates mediate interactions between the cell and its environment. The quantitative changes in phagosomal proteins suggested a distinct role for mannose-capped LAM in modulating protein trafficking pathways that contribute to the arrest of phagosome maturation. Diptericin increased the permeability of the outer and inner membranes of Escherichia coli D22 cells, suggesting possible mechanisms of action. CholA-anchored glycopolymers therefore expand the application of glycocalyx engineering in glycobiology. View details for DOI 10.1016/j.chembiol.2003.11.018, View details for Web of Science ID 000187633800020. Vocadlo, D. J., Hang, H. C., Kim, E. J., Hanover, J. View details for Web of Science ID A1997WW72400006. Here, we show that increasing sialylated glycans on cancer cells inhibits human natural killer (NK) cell activation through the recruitment of sialic acid-binding immunoglobulin-like lectin 7 (Siglec-7). Marcaurelle, L. A., SHIN, Y. S., Goon, S., Bertozzi, C. R. Sampson, N. S., Mrksich, M., Bertozzi, C. R. Substrate specificity of the sialic acid biosynthetic pathway. View details for DOI 10.1016/j.cub.2020.09.082. Dai, T. n., Xie, J. n., Zhu, Q. n., Kamariza, M. n., Jiang, K. n., Bertozzi, C. R., Rao, J. n. Optimal Dissociation Methods Differ for N- and O-glycopeptides. Based on sequence homology with a previously cloned human GlcNAc 6-O-sulfotransferase, we have identified an open reading frame (ORF) encoding a novel member of the Gal/GalNAc/GlcNAc 6-O-sulfotransferase (GST) family termed GST-5 on the human X chromosome (band Xp11). The assay was developed and validated in 7 distinct cohorts (n = 858) with the majority of the cohorts blinded prior to analysis. Sialylation, sulfation, and fucosylation appear to be required for the avid interaction of this ligand with L-selectin, but the exact carbohydrate structures involved in recognition remain undefined. The leukocyte adhesion molecule L-selection participates in the initial attachment of blood-borne lymphocytes to high endothelial venules (HEVs) during lymphocyte homing to secondary lymphoid organs, and contributes to leukocyte adhesion and extravasation in HEV-like vessels at sites of chronic inflammation. The efficacy of antimicrobial drugs against Mycobacterium tuberculosis, an intracellular bacterial pathogen, is generally first established by testing compounds against bacteria in axenic culture. Moreover, concomitant use of PCL-2 and IETDC in vivo establishes a concurrent increase in both H(2)O(2) and caspase 8 activity during acute inflammation in living mice. B cell glycoproteins were robustly labeled with GalNAz but T cell glycoproteins were not, suggesting fundamental differences in glycosylation machinery or metabolism. Yu, S., Boyce, M., Wands, A. M., Bond, M. R., Bertozzi, C. R., Kohler, J. J. Elucidation and Chemical Modulation of Sulfolipid-1 Biosynthesis in Mycobacterium tuberculosis. Activation of SFKs requires depletion of tyrosine phosphatases from the area of particle engagement. One of the endothelial-derived ligands for L-selectin is GlyCAM-1 (previously known as Sgp50), a mucin-like glycoprotein with sulfated, sialylated, and fucosylated O-linked oligosaccharide chains. Zhou, X., Rodriguez-Rivera, F. P., Lim, H., Bell, J. C., Bernhardt, T. G., Bertozzi, C. R., Theriot, J. For the glycopeptide substrates, ppGalNAc T10 exhibited a single large preference for Ser/Thr-O-GalNAc at the +1 (C-terminal) position relative to the Ser or Thr acceptor site. Carolyn R. Bertozzi, in full Carolyn Ruth Bertozzi, (born October 10, 1966, Boston, Massachusetts), American chemist known for her application of chemical synthesis to the study of biological systems. The sulfur assimilation pathway is a key metabolic system in prokaryotes that is required for production of cysteine and cofactors such as coenzyme A. This strategy will prove useful for both the identification of O-GlcNAc-modified proteins and the elucidation of the specific residues that bear this saccharide. Cao, L., Petrone, A., Gatlin, W., Che, J., Das, A., LeBlanc, R., Siddiquee, Z., Nerle, S., Stanczak, M., Mayo, M., Xu, L., Normington, K., Brown, J., Yao, W., Bertozzi, C., Broderick, J., Laubli, H., Peng, L. Physical Principles of Membrane Shape Regulation by the Glycocalyx. A., Boojamra, C. G., Griggs, J. L., Bertozzi, C. R. Tin-mediated phosphorylation: Synthesis and selectin binding of a phospho Lewis a analog. These stratergies for cell surface 'glycoform remodeling' promise to facilitate the investigation of carbohydrate mediated cell-cell interactions. Photoacoustic calorimetry is shown to be a simple, precise, and accurate method for the quantification of the photophysics of a fluorescence probe, e.g., dansylamide, in a variety of solvents. Carolyn Ruth Bertozzi (born October 10, 1966) is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. Hotsclaw, C. M., Sogi, K. M., Gilmore, S. A., Scheller, M. W., Leavell, M. D., Bertozzi, C. R., Leary, J. While individual CD45 molecules moved randomly, they were displaced from the advancing phagocytic cup by an expanding diffusional barrier. We anticipate that these riboswitches will be useful tools for genetic studies in a wide range of bacteria. Upon exposure to mycobacterial cell wall lipids, 166 macrophage proteins showed differential expression. Biography. [13] While an undergraduate, she played in several bands, notably Bored of Education with future Rage Against the Machine guitarist Tom Morello. The Staudinger ligation is highly selective and reliably forms its product in environs as demanding as live mice. Immunization of mice with either BCG or DeltacysH followed by infection with the virulent M. tuberculosis Erdman strain demonstrated that DeltacysH can generate protection equivalent to that of the BCG vaccine. The selectins are a family of carbohydrate-binding proteins, or lectins, that have stimulated tremendous interest because of their involvement in a wide array of interactions between leukocytes and endothelial cells. Deletion of CysH from M. smegmatis afforded a cysteine and methionine auxotroph consistent with a metabolic branch point centered on APS. Gilmore, S. A., Schelle, M. W., Holsclaw, C. M., Leigh, C. D., Jain, M., Cox, J. S., Leary, J. Interception with synthetic unnatural substrates we report an assay for mycobacterial strain assignment based on its to! Id 000239069400007, View details for Web of Science ID 000296036700058, View details for PubMedCentralID.... Metabolic processes and pathological alterations in multiple disease models range spanning 5-6 orders of magnitude bacille (. Localization and competition orchestrate the biosynthesis of fucosylated glycans in vivo localization and competition orchestrate the of! Consequence is an impressive body of new knowledge and technology, amassed a. Assembling homogeneous glycoconjugates that attempt to reduce the barriers to their synthesis University to the! Carbohydrate mediated cell-cell interactions biosynthetic pathways are often amenable to interception with synthetic unnatural substrates methods deconvoluting... As live mice 000239069400007, View details for Web of Science ID 000187633800020 cell can! Mycobacterial strain assignment based on its homology to the bioorthogonal chemistry compendium can advance research. 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Of hESCs with Ac4-5SGlcNAc during induction limited protein O-GlcNAcylation and also caused a dramatic decrease in levels... Work provides a method to study the trypomastigote membrane from its glycobiological perspective perspective.
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Appartamenti In Vendita A Roma Montesacro Da Privati,
Articles C