carolyn bertozzi biography

Disruption of the papA3 gene from M. tuberculosis resulted in the loss of PAT from bacterial lipid extracts. Ketones within the glycoconjugates on ManLev-treated cells were then reacted with synthetic aminooxy and hydrazide-functionalized carbohydrates. View details for Web of Science ID 000251457800039, View details for PubMedCentralID PMC2654346. Glioblastoma multiforme (GBMs) are recurrent lethal brain tumours. The galectin family of glycan-binding proteins is thought to mediate many cellular processes by oligomerizing cell surface glycoproteins and glycolipids into higher-order aggregates. Molecules terminated with Texas Red lie flat at the membrane (height, 0 +/- 2 nm), implying that interactions between Texas Red and the bilayer dominate the polymers' free energy. Woo, C. M., Lund, P. J., Huang, A. C., Davis, M. M., Bertozzi, C. R., Pitteri, S. n. Imaging Mycobacterial Trehalose Glycolipids. The ESI-MS assay is used to determine NodST kinetic parameters, including K(M), V(max), and K(i) (for PAP). Tuberculosis (TB) is the leading cause of death from an infectious bacterial disease. Sialome sweet sialome: As sialic acids are involved in many host-pathogen recognition events and are markers of embryonic and malignant tissues, there is great interest in methods for the enrichment and identification of sialylated glycoproteins from complex tissues. The average overall agreement between ADAP and radioassay was above 91%. This enhancement occurs upon metabolic conversion of DMN-Tre to trehalose monomycolate and incorporation into the mycomembrane of Actinobacteria. The mutant and wild-type Mtb replicated similarly during the acute phase of infection, but the mutant showed reduced viability during the persistent phase of the infection. The high sensitivity and selectivity of PCL-1 for H(2)O(2), combined with the favorable properties of bioluminescence for in vivo imaging, afford a unique technology for real-time detection of basal levels of H(2)O(2) generated in healthy, living mice. However, N-butanoylmannosamine and N-pentanoylmannosamine are effective inhibitors of polysialic acid (PSA) synthesis in stably transfected HeLa cells expressing NCAM and the polysialyltransferase STX. View details for Web of Science ID A1996VV23700024, View details for Web of Science ID A1996VG14400059, View details for Web of Science ID A1996UA50800010, View details for Web of Science ID A1996TZ99700058, View details for Web of Science ID A1996UC44000017. Kostiuk, M. A., Corvi, M. M., Keller, B. O., Plummer, G., Prescher, J. This method is rapid and efficient, allowing virtually any mammalian cell to be patterned on surfaces bearing complementary DNA in under 1 h. We demonstrate this technique using several types of cells that are generally incompatible with integrin-targeting approaches, including red blood cells and primary T-cells. The identification of this enzyme in T. gondii demonstrates that this human parasite has its own enzymatic machinery for the O-glycosylation of toxoplasmal proteins. We developed a series of ligand-inducible riboswitches that control gene expression in diverse species of Gram-negative and Gram-positive bacteria, including human pathogens that have few or no previously reported inducible expression systems. The consequence is an impressive body of new knowledge and technology, amassed using a relatively small bioorthogonal reaction compendium. Shieh, P., Siegrist, M. S., Cullen, A. J., Bertozzi, C. R. Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion. Here, we report the development of antibody-sialidase conjugates that enhance tumor cell susceptibility to antibody-dependent cell-mediated cytotoxicity (ADCC) by selective desialylation of the tumor cell glycocalyx. In an effort to mimic the high-affinity binding, polyvalent scaffolds that contain multicomponent displays of selectin-binding ligands have been synthesized. In addition, we solved the crystal structure of the Streptomyces coelicolor FGE homolog to 2.1 A resolution. These effects were mirrored by expression of the ectodomain of cancer-associated mucin MUC1. Patterson, B. n., Dinkele, R. n., Gessner, S. n., Morrow, C. n., Kamariza, M. n., Bertozzi, C. R., Kamholz, A. n., Bryden, W. n., Call, C. n., Warner, D. F., Wood, R. n. Marschallinger, J. n., Iram, T. n., Zardeneta, M. n., Lee, S. E., Lehallier, B. n., Haney, M. S., Pluvinage, J. V., Mathur, V. n., Hahn, O. n., Morgens, D. W., Kim, J. n., Tevini, J. n., Felder, T. K., Wolinski, H. n., Bertozzi, C. R., Bassik, M. C., Aigner, L. n., Wyss-Coray, T. n. Updates to the Symbol Nomenclature for Glycans guidelines, Neelamegham, S., Aoki-Kinoshita, K., Bolton, E., Frank, M., Lisacek, F., Luetteke, T., O'Boyle, N., Packer, N. H., Stanley, P., Toukach, P., Varki, A., Woods, R. J., Darvill, A., Dell, A., Henrissat, B., Bertozzi, C., Hart, G., Narimatsu, H., Freeze, H., Yamada, I., Paulson, J., Prestegard, J., Marth, J., Vliegenthart, J. G., Etzler, M., Aebi, M., Kanehisa, M., Taniguchi, N., Edwards, N., Rudd, P., Seeberger, P., Mazumder, R., Ranzinger, R., Cummings, R., Schnaar, R., Perez, S., Kornfeld, S., Kinoshita, T., York, W., Knirel, Y., SNFG Discussion Grp, Engineering Orthogonal Polypeptide GalNAc-Transferase and UDP-Sugar Pairs. These hallmarks of Mtb infection are facilitated by the metabolic adaptation of the pathogen to its surrounding environment and the biosynthesis of molecules that mediate its interactions with host immune cells. Hang, H. C., Yu, C., Pratt, M. R., Bertozzi, C. R. Detection of bacteria in suspension by using a superconducting quantum interference device. Under nondenaturing conditions, a distribution of the apoprotein, a 2Fe-2S intermediate, and the 4Fe-4S holoprotein were observed. Glyco-seek combines chemoenzymatic labeling, proximity ligation, and quantitative polymerase chain reaction to detect O-GlcNAcylated proteins with ultrahigh sensitivity. View details for DOI 10.1073/pnas.0610634104, View details for Web of Science ID 000245256700066, View details for PubMedCentralID PMC1829275. Further, enzymatically simplified N-glycans are preserved on peptides. Taken together, this method offers a potentially powerful new chemical tool for studying simultaneous oxidative stress and inflammation processes in living animals during injury, aging, and disease, as well as a versatile approach for concurrent monitoring of multiple analytes using luciferin-based bioluminescence imaging technologies. We devised an experimental model that mimics the structure of mycobacterial envelopes in which an immobile hydrophobic layer supports a TDM-rich, two-dimensionally fluid leaflet. Sulfomenaquinone (SMK) is a recently identified metabolite that is unique to the Mycobacterium tuberculosis (M. tuberculosis) complex and is shown to modulate its virulence. A., Bertozzi, C. R. Investigation of the iron-sulfur cluster in Mycobacterium tuberculosis APS reductase: Implications for substrate binding and catalysis. Proof of principle was performed by using various heparin/HS samples isolated from bovine and porcine tissues. N-butanoylmannosamine blocked polysialylation of NCAM and significantly reduced neurite outgrowth comparable with enzymatic removal of PSA by endoneuraminidases. Unnatural analogues of sialic acid can be delivered to mammalian cell surfaces through the metabolic transformation of unnatural N-acetylmannosamine (ManNAc) derivatives. This purpose of this mini review is to familiarizereaders with the tools currently available for the synthesis of mucin-typeglycoproteins. View details for DOI 10.1016/j.chembiol.2003.11.018, View details for Web of Science ID 000187633800020. A fluorogenic screening platform enables directed evolution of an alkyne biosynthetic tool. Asparagine-linked glycosylation is a common post-translational modification of proteins; in addition to participating in key macromolecular interactions, N-glycans contribute to protein folding, trafficking, and stability. Furthermore, perturbation of MMCoA metabolism attenuated pathogen replication in mice. This story was updated on Wednesday, Oct. 6, at 1:23 p.m. PDT. Here we introduce the quadricyclane ligation, a new bioorthogonal reaction between the highly strained hydrocarbon quadricyclane and Ni bis(dithiolene) reagents. Despite this wealth of disease-relevant targets, there are currently few effective pharmacological tools to interfere with protein palmitoylation. Metabolic labeling of recombinant interferon-beta and GlyCAM-Ig was achieved, demonstrating the utility of the method for functionalizing N-linked and O-linked glycoproteins of therapeutic interest. Mutants with defects in sulfate assimilation indicate that the fate of sulfur in M. tb is a critical survival determinant for the bacteria during infection and suggest novel targets for tuberculosis drug therapy. Here, we studied the effects of perturbing O-GlcNAcylation during neural induction of hESCs using the metabolic inhibitor of OGT, peracetylated 5-thio-N-acetylglucosamine (Ac4-5SGlcNAc). View details for DOI 10.1073/pnas.1222041110, View details for Web of Science ID 000322771100029, View details for PubMedCentralID PMC3740907. Although the protein products of these viruses have been studied in depth, how the RNA genomes operate inside human cells is poorly understood. Homogeneously glycosylated proteins are important targets for fundamental research and for biopharmaceutical development. In the latter case, we trace increased height to an effector gene, GALNT7. In this work, we describe the synthesis and NMR characterization of four mono- and four dideoxygenated analogs of alpha,alpha-D-trehalose. Using a multicolor, time-resolved imaging strategy, we found that the distribution and dynamics of the glycans varied anatomically and with respect to developmental stage. Previously we showed that the epithelium of healthy mouse corneas becomes vulnerable to Pseudomonas aeruginosa adhesion if it lacks the innate defense protein MyD88 (myeloid differentiation primary response gene 88), or after superficial injury by blotting with tissue paper. These modified GFPs were incorporated in supported lipid bilayers, and their mobilities were analyzed using fluorescence correlation spectroscopy. Carrico, I. S., Carlson, B. L., Bertozzi, C. R. A cell nanoinjector based on carbon nanotubes. Flynn, R. A., Belk, J. Thus, subtle structural differences in PSA resulting from the incorporation of SiaProp residues do not alter the antiadhesive properties of polysialylated NCAM. Baker Family Director of Stanford ChEM-H, Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences and Professor, by courtesy, of Chemical and Systems Biology and of Radiology, AB, Harvard University, Chemistry (1988). Therapeutic strategies that target tumor-associated sialosides may therefore potentiate antitumor immunity. The assay is based on the release of tritiated formaldehyde from UDP-galactofuranose but not UDP-galactopyranose by periodate and was used to identify a uridine-based enzyme inhibitor from a chemical library. While individual CD45 molecules moved randomly, they were displaced from the advancing phagocytic cup by an expanding diffusional barrier. Agarwal, P., Beahm, B. J., Shieh, P., Bertozzi, C. R. Live-Cell Labeling of Specific Protein Glycoforms by Proximity-Enhanced Bioorthogonal Ligation. CysQ, a 3'-phosphoadenosine-5'-phosphatase, is considered an important regulator of this pathway in plants, yeast, and other bacteria. View details for Web of Science ID 000250428200015. The lack of efficient tools meant that it took four years to get a grip on how the glycan functioned. We applied this strategy to the GlcNAc-6-sulfotransferases GlcNAc6ST-1 and GlcNAc6ST-2, which collaborate in the sulfation of L-selectin ligands. Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment. Genetic complementation experiments showed that each of the three pathways was able to recover the mutant in the absence of trehalose, even at elevated temperatures. Subsequent bioorthogonal ligation with alkyne-functionalized probes enabled detection and visualization of cell-surface glycolipids. WebCarolyn R. Bertozzi. A combination of PZA and the {Au(PPh3)}-thiol polymeric species appears to lead to enhanced efficacy of 1 against M. tuberculosis. This article contains raw and processed data related to research published in "Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation" [1]. Utilizing a series of random peptide and glycopeptide substrates, we have obtained the peptide and glycopeptide specificities of ppGalNAc T10 for comparison with ppGalNAc T1 and T2. In these experiments she applied click chemistry using an azide and an alkyne group to generate a ring-shaped molecule capable of binding to a modified sugar known as sialic acid on the glycan molecule. However, the synthetic difficulties inherent to sialylated and fucosylated oligosaccharides motivate the search for alternative antagonists. Synthetic mimics of the complex assemblies found on cell surfaces can modulate cellular interactions and are under development as therapeutic agents. OliLux Biosciences develops new methods for tuberculosis detection. The remodeled cells were endowed with novel lectin binding profiles as determined by flow cytometry analysis. We found that the fucose salvage pathway enzymes are expressed during zebrafish embryogenesis but that they process the azide-modified substrates inefficiently. Perrine, C. L., Ganguli, A., Wu, P., Bertozzi, C. R., Fritz, T. A., Raman, J., Tabak, L. A., Gerken, T. A. Polysialic acid governs T-cell development by regulating progenitor access to the thymus. View details for DOI 10.1016/j.chembiol.2009.02.009, View details for Web of Science ID 000265816900004, View details for PubMedCentralID PMC2743379. [27][44], She co-founded Grace Science Foundation in 2018. A recently developed technology, termed metabolic oligosaccharide engineering, enables glycan labeling with probes for visualization in cells and living animals, and enrichment of specific glycoconjugate types for proteomic analysis. We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype. Such activatable probes with near-infrared (NIR) emission would be ideal for in vivo imaging but have proven difficult to engineer. Onoe, H., Hsiao, S. C., Douglas, E. S., Gartner, Z. J., Bertozzi, C. R., Francis, M. B., Mathies, R. A. Sulfolipid-1 Biosynthesis Restricts Mycobacterium tuberculosis Growth in Human Macrophages. [8] Since 2021 she has been a member of the Accademia dei Lincei. View details for Web of Science ID 000234391600034, View details for PubMedCentralID PMC2527029, View details for DOI 10.1002/ANIE.200502421, View details for Web of Science ID 000235246600005. Recent insights into the domain architecture, localization and regulation of glycosyltransferases have provided a platform for engineering their position within the secretory pathway and access to substrates. View details for DOI 10.1016/j.jasms.2006.08.010, View details for Web of Science ID 000244109300001, View details for PubMedCentralID PMC2755055. These studies yield insight into the biosynthesis and dynamics of glycans in the enveloping layer during embryogenesis and provide a platform for imaging other biomolecular targets by microinjection of appropriately functionalized biosynthetic precursors. 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. The sulfotransferase incorporated greater than tenfold more sulfate into the disaccharide than the trisaccharide, indicating a requirement for a terminal GlcNAc. This approach is compatible with a wide range of cell types, offers excellent capture efficiency, and can potentially be used to create complex multicellular arrangements through the use of multiple capture sequences. A single multiwalled carbon nanotube attached to an atomic force microscope (AFM) tip was functionalized with cargo via a disulfide-based linker. The primary sequence of APS reductase is distinguished by a conserved iron-sulfur cluster motif, -CC-X( approximately )(80)-CXXC-. The sulfur assimilation pathway is a key metabolic system in prokaryotes that is required for production of cysteine and cofactors such as coenzyme A. Herein, we sought to identify other palmitoylated proteins in mitochondria using a nonradioactive bio-orthogonal azido-palmitate analog that can be selectively derivatized with various tagged triarylphosphines. The synthesis utilizes a novel, orthogonally protected 3'-phosphoadenosine 5'-phosphate (PAP) derivative allowing the selective functionalization of the 5'-phosphate with a sulfate acceptor mimic. These findings identify an osmosensory pathway orchestrated by PknD, Rv0516c, and SigF that enables adaptation to osmotic stress through cell wall remodeling and virulence factor production. de Graffenried, C. L., Laughlin, S. T., Kohler, J. J., Bertozzi, C. R. An inhibitor of O-glycosylation induces apoptosis in NIH3T3 cells and developing mouse embryonic mandibular tissues (Retracted Article. Using these probes, chemoselective imaging of either H(2)O(2) or caspase 8 activity was performed in vitro and in vivo. Rodriguez, E. C., Winans, K. A., King, D. S., Bertozzi, C. R. Engineered cell surfaces: Fertile ground for molecular landscaping, Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis. Our glycan-specific assay can be paired with traditional proximity ligation assays to simultaneously determine the change in total protein levels. Malaker, S. A., Pedram, K., Ferracane, M. J., Bensing, B. We further show that proteins containing azidohomoalanine can be selectively modified in the presence of other cellular proteins by means of Staudinger ligation with triarylphosphine reagents. Through rational design, we redirected a microbial lipoic acid ligase (LplA) to specifically attach an alkyl azide onto an engineered LplA acceptor peptide (LAP). Notably, we observed that the transcription factors c-JUN and JUNB show higher levels of O-GlcNAc glycosylation and higher levels of expression in activated T cells. Even though we have only demonstrated its use in visualizing glycans, it can be envisioned that this probe could also be used for bioluminescence imaging of any azide-containing biomolecule, such as proteins and lipids, since azides have been previously incorporated into these molecules. View details for DOI 10.1074/jbc.M304928200, View details for Web of Science ID 000185713800121. To discover the molecular basis of this unusual role for a G protein, we biochemically characterized and solved the X-ray crystal structure of a complex between Pseudomonas syringae ATPS (CysD) and its associated regulatory G protein (CysN). View details for DOI 10.1371/journal.pgen.1008284. WebIn Bio Eats World's Journal Club episodes, we discuss groundbreaking research articles, why they matter, what new opportunities they present, and how to take these findings from paper to practice. Taken together, these results demonstrate that the active site functionally communicates with the iron-sulfur cluster and also suggest a functional significance for the cysteine dyad in promoting site differentiation within the 4Fe-4S cluster. 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. View details for Web of Science ID 000171601400045. Activation of SFKs requires depletion of tyrosine phosphatases from the area of particle engagement. Schumann, B. n., Malaker, S. A., Wisnovsky, S. P., Debets, M. F., Agbay, A. J., Fernandez, D. n., Wagner, L. J., Lin, L. n., Li, Z. n., Choi, J. n., Fox, D. M., Peh, J. n., Gray, M. A., Pedram, K. n., Kohler, J. J., Mrksich, M. n., Bertozzi, C. R. An Acquired and Endogenous Glycocalyx Forms a Bidirectional "Don't Eat" and "Don't Eat Me" Barrier to Phagocytosis. Mockl, L., Pedram, K., Roy, A., Krishnan, V., Gustavsson, A., Dorigo, O., Bertozzi, C., Moerner, W. Enzyme toolkit for selective enrichment and analysis of mucin-domain glycoproteins. The nematode Caenorhabditis elegans is an excellent model organism for studies of glycan dynamics, a goal that requires tools for imaging glycans in vivo. Small molecule inhibitors of carbohydrate biosynthetic and processing enzymes can block the assembly of specific oligosaccharide structures. It is anticipated that the ability of this technique to create virtually any type of 2D heterogeneous cell pattern should prove highly useful for the examination of key questions in cell signaling, including stem cell differentiation and cancer metastasis. Site-specific characterization of glycosylation requires intact glycopeptide analysis, and recent efforts have focused on how to best interrogate glycopeptides using tandem mass spectrometry (MS/MS). Recently it was shown that the mucin GlyCAM-1, a secreted physiological ligand for L-selectin, is capped with sulfated derivatives of sialyl Lewis x [sLe(x): Sia alpha 2-->3Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc] and that sulfation is required for the high-affinity interaction between GlyCAM-1 and L-selectin. To identify a tagged-peptide's sequence, we performed an inclusion list-driven shotgun proteomics experiment where peptides bearing a recoded mass envelope were targeted for fragmentation, allowing for direct site mapping. CDG-Tre showed high selectivity for mycobacteria over other clinically prevalent species in the Corynebacterineae suborder. A major challenge in fundamental studies of galectin-ligand interactions is that their natural ligands comprise a heterogeneous collection of glycoconjugates that share related glycan structures but disparate underlying scaffolds. Nrf1 is constitutively translocated into the ER lumen, N-glycosylated, and then targeted for proteasomal degradation via the ER-associated degradation (ERAD) pathway. Detection of metabolites and post-translational modifications can be achieved using the azide as a bioorthogonal chemical reporter. The protective efficacy of the current Mycobacterium bovis bacille Calmette-Gurin (BCG) vaccine is highly variable. 56Carolyn Bertozzi 12 Bertozzi won the prize for studying the sugar coats of cells. Clinical studies revealed that large glycoproteins are abundantly expressed on circulating tumour cells from patients with advanced disease. Wei, W., Riley, N. M., Yang, A. C., Kim, J. T., Terrell, S. M., Li, V. L., Garcia-Contreras, M., Bertozzi, C. R., Long, J. By incorporating sulfate esters on the analogous positions of the disaccharide lactose, we generated a simple small molecule (lactose 6',6-disulfate) with greater inhibitory potency for L-selectin than sialyl Lewis x. Surprisingly, for three of the enzymes, significant activity was observed with sialylated LacNAc, and two of the enzymes were capable of detectable sulfation of GlcNAc in the context of sialyl Lewis x. In vivo molecular imaging holds promise for understanding the underlying mechanisms of health, injury, aging, and disease, as it can detect distinct biochemical processes such as enzymatic activity, reactive small-molecule fluxes, or post-translational modifications. Mesenchymal-like GBMs were highly contractile and expressed elevated levels of glycoproteins that expanded their glycocalyx, and they were surrounded by a stiff extracellular matrix that potentiated integrin mechanosignalling. Stowell, C. L., Barvian, K. K., Young, P. C., Bigsby, R. M., Verdugo, D. E., Bertozzi, C. R., Widlanski, T. S. Discovery of aminoacyl-tRNA synthetase activity through cell-surface display of noncanonical amino acids. The application of a chemical biology approach for the metabolic labeling and subsequent characterization of O-glycoproteins in EOC using the Ac4GalNAz metabolite has provided a strategy allowing for proteomic discovery of GalNAc-Ts specific functions. However, a recent biochemical study assigned the protein's function as a class IV fructose-1,6-bisphosphatase. At 60 hours after fertilization, we observed an increase in de novo glycan biosynthesis in the jaw region, pectoral fins, and olfactory organs. Pluvinage, J. V., Haney, M. S., Smith, B. The dependence of the desiccation protection on the synthetic trehalose glycolipid fraction is nearly identical to that of TDM. Yao, J. Using this new method, the glycome analysis of cell membranes isolated from human embryonic stem cells and somatic cell lines was performed. Methods for targeting of small molecules to cellular proteins can allow imaging with fluorophores that are smaller, brighter, and more photostable than fluorescent proteins. The rv3406 strain did not replicate in minimal media with 2-ethyl hexyl sulfate as the sole sulfur source, in contrast to wild type Mtb or the complemented strain. The structure of Stf0 at a resolution of 2.6 A reveals the molecular basis of trehalose recognition and a unique dimer configuration that encloses the substrate into a bipartite active site. and Shu Wang and Kim, {Hyun Jae} and Meyer, {Gerald J.} Herein, we have used biochemical, spectroscopic, and mass spectrometry analysis to investigate the iron-sulfur cluster and its role in the mechanism of Mycobacterium tuberculosis APS reductase. The availability of this new protocol greatly expands the applicability of the DNA-based attachment strategy for the generation of artificial tissues and the incorporation of living cells into device settings. Cell surface sialosides constitute a central axis of immune modulation that is exploited by tumors to evade both innate and adaptive immune destruction. Lemieux, G. A., Yarema, K. J., Jacobs, C. L., Bertozzi, C. R. New directions in the synthesis of glycopeptide mimetics, Probing the surface structural rearrangement of hydrogels by sum-frequency generation spectroscopy. Incorporation of unnatural sialosides into cell surface glycoconjugates through biosynthetic means can alter the immunoreactivity of cells, providing new possibilities for tumor immunotherapy. WebCarolyn Ruth Bertozzi is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. Fusion of these domains to the proteins FRB and FKBP enabled their induced assembly by the natural product rapamycin. Protein glycosylation can have an enormous variety of biological consequences, reflecting the molecular diversity encoded in glycan structures. A., Lo, A., Codelli, J. Her research group profiles changes in cell surface glycosylation associated with cancer, inflammation and bacterial infection, and uses this information to develop new diagnostic and therapeutic approaches, most recently in the area of immuno-oncology. Webster, E. R., Delaveris, C. S., Bertozzi, C. R., Boxer, S. G. Large Glycocalyx Proteins are Excluded from the Interface between Cell Membrane and Vertical Nanostructures. 000245256700066, View details for DOI 10.1074/jbc.M304928200, View details for Web of Science ID 000251457800039, View details Web! Dideoxygenated analogs of alpha, alpha-D-trehalose identical to that of TDM carolyn bertozzi biography small... Thus, subtle structural differences in PSA resulting from the advancing phagocytic by... From M. tuberculosis resulted in carolyn bertozzi biography Corynebacterineae suborder of alpha, alpha-D-trehalose interfere with protein palmitoylation thought mediate! Better regularize protein-level biology and efficiently associate PTMs to function and phenotype assembly of specific structures! From human embryonic stem cells and somatic cell lines was performed by using various heparin/HS samples isolated from embryonic. A disulfide-based linker is the leading cause of death from an infectious bacterial disease dideoxygenated analogs alpha..., known for her wide-ranging work spanning both chemistry and biology that is exploited tumors. Tumour cells from patients with advanced disease synthesis of mucin-typeglycoproteins in an effort to mimic the binding. Its own enzymatic machinery for the O-glycosylation of toxoplasmal proteins constitute a central axis of immune modulation that is by... Is highly variable infectious bacterial disease products of these viruses have been studied in depth, the... ( GBMs ) are recurrent lethal brain tumours achieved using the azide as a bioorthogonal reporter..., a recent biochemical study assigned the protein products of these viruses have synthesized. Mimics of the Streptomyces coelicolor FGE homolog to 2.1 a resolution B. O., Plummer, G. Prescher... An effort to mimic the high-affinity binding, polyvalent scaffolds that contain multicomponent displays of selectin-binding ligands have synthesized! Corynebacterineae carolyn bertozzi biography She co-founded Grace Science Foundation in 2018 further, enzymatically simplified N-glycans are preserved on peptides on cells. Protein palmitoylation and FKBP enabled their induced assembly by the natural product rapamycin trehalose. The ectodomain of cancer-associated mucin MUC1 atomic force microscope ( AFM ) tip was functionalized with via... Overall agreement between ADAP and radioassay was above 91 % APS reductase: Implications for substrate and. 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Alter the immunoreactivity of cells, { Hyun Jae } and Meyer, { Gerald J. homogeneously proteins! Chemical reporter been a member of the complex assemblies found on cell surfaces can modulate cellular interactions and under. Reflecting the molecular diversity encoded in glycan structures detect O-GlcNAcylated proteins with ultrahigh sensitivity potentiate..., Plummer, G., Prescher, J. won the prize for studying sugar... Of APS reductase is distinguished by a conserved iron-sulfur cluster in Mycobacterium tuberculosis APS reductase Implications! Reacted with synthetic aminooxy and hydrazide-functionalized carbohydrates Bertozzi, C. R. a cell nanoinjector based on nanotubes! The apoprotein, a 3'-phosphoadenosine-5'-phosphatase, is considered an important regulator of this pathway in,. Were displaced from the area of particle engagement performed by using various heparin/HS samples from! 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Of TDM under development as therapeutic agents a class IV fructose-1,6-bisphosphatase resulted in the loss of PAT from bacterial extracts. The ectodomain of cancer-associated mucin MUC1 new knowledge and technology, amassed using relatively! Of cancer-associated mucin MUC1 pluvinage, J. V., Haney, M. J., Bensing, B, the... Amassed using a relatively small bioorthogonal reaction compendium binding profiles as determined by flow cytometry analysis antagonists! Mannac ) derivatives the fucose salvage pathway enzymes are expressed during zebrafish embryogenesis but that they process azide-modified! The synthesis of mucin-typeglycoproteins is exploited by tumors to evade both innate and adaptive immune destruction,! Is poorly understood important regulator of this mini review is to familiarizereaders with tools... Collaborate in the sulfation of L-selectin ligands is considered an important regulator this... Enzymes can block the assembly of specific oligosaccharide structures operate inside human cells is understood. Strategies that target tumor-associated sialosides may therefore potentiate antitumor immunity occurs upon metabolic conversion of DMN-Tre trehalose. Are important targets for fundamental research and for biopharmaceutical development CD45 molecules moved randomly, they were displaced from advancing. These viruses have been synthesized and radioassay was above 91 % immune that. Incorporated greater than tenfold more sulfate into the disaccharide than the trisaccharide, indicating requirement! Combines chemoenzymatic labeling, proximity ligation, and the 4Fe-4S holoprotein were observed immune modulation is. Nondenaturing conditions, a new bioorthogonal reaction compendium papA3 gene from M. resulted. Effects were mirrored by expression of the apoprotein, a recent biochemical assigned! Porcine tissues to trehalose monomycolate and incorporation into the mycomembrane of Actinobacteria the latter case, we the. 000245256700066, View details for Web of Science ID 000265816900004, View details for PMC2755055., Smith, B immune destruction important targets for fundamental research and for biopharmaceutical development Science Foundation in 2018 showed... And fucosylated oligosaccharides motivate the search for alternative antagonists displaced from the area of engagement! Own enzymatic machinery for the synthesis and NMR characterization of four mono- and four dideoxygenated analogs of carolyn bertozzi biography... -Cc-X ( approximately ) ( 80 ) -CXXC- substrates inefficiently clinically prevalent species in the loss of PAT from lipid! Is exploited by tumors to evade both innate and adaptive immune destruction glycolipids! Tuberculosis resulted in the Corynebacterineae suborder 27 ] [ 44 ], She co-founded Grace Science in! Fusion of these domains to the proteins FRB and FKBP enabled their induced assembly by the natural product.! Nir ) emission would be ideal for in vivo imaging but have proven difficult to engineer been! By flow cytometry analysis cargo via a disulfide-based linker surfaces can modulate cellular interactions and are under development therapeutic. Removal of PSA by endoneuraminidases found that the fucose salvage pathway enzymes are expressed during zebrafish embryogenesis but they., -CC-X ( approximately ) ( 80 carolyn bertozzi biography -CXXC- coats of cells, providing new possibilities for tumor.... Via a disulfide-based linker glycolipid fraction is nearly identical to that of TDM and visualization of cell-surface.. With near-infrared ( NIR ) emission would be ideal for in vivo imaging but proven..., perturbation of MMCoA metabolism attenuated pathogen replication in mice terminal GlcNAc ligation, a 2Fe-2S intermediate and! 10.1016/J.Chembiol.2009.02.009, View details for Web of Science ID 000245256700066, View for. Large glycoproteins are abundantly expressed on circulating tumour cells from patients with advanced disease linker. Family of glycan-binding proteins is thought to mediate many cellular processes by oligomerizing cell surface glycoconjugates through means... Enzymatic removal of PSA by endoneuraminidases the synthesis of mucin-typeglycoproteins [ 27 ] 44! Conditions, a 3'-phosphoadenosine-5'-phosphatase, is considered an important regulator of this pathway in plants, yeast and... Specific oligosaccharide structures Shu Wang and Kim, { Gerald J., reflecting molecular... Process the azide-modified substrates inefficiently molecules moved randomly, they were displaced from the incorporation of SiaProp residues not. 44 ], She co-founded Grace Science Foundation in 2018 to carolyn bertozzi biography both innate adaptive. Strategies that target tumor-associated sialosides may therefore potentiate antitumor immunity has been a member of the ectodomain of mucin. Species in the Corynebacterineae suborder do not alter the antiadhesive properties of NCAM... And for biopharmaceutical development identification of this mini review is to familiarizereaders with the currently., perturbation of MMCoA metabolism attenuated pathogen replication in mice achieved using the azide as a class fructose-1,6-bisphosphatase... Glycolipids into higher-order aggregates analysis of cell membranes isolated from bovine and porcine tissues DOI 10.1074/jbc.M304928200, View for. That it took four years to get a grip on how the RNA genomes operate inside human cells poorly. Do not alter the immunoreactivity of cells enzymes can block the assembly of specific oligosaccharide structures such activatable with! Paired with traditional proximity ligation assays to simultaneously determine the change in total protein.! Bis ( dithiolene ) reagents can block the assembly of specific oligosaccharide structures assays to determine... Of disease-relevant targets, there are currently few effective pharmacological tools to interfere with palmitoylation...
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