Woo, C. M., Iavarone, A. T., Spiciarich, D. R., Palaniappan, K. K., Bertozzi, C. R. The cancer glycocalyx mechanically primes integrin-mediated growth and survival. GST-5 was also expressed in soluble epitope-tagged form and found to catalyze 6-O-sulfation of GlcNAc residues in synthetic acceptor structures. Additionally, we have utilized computational methods to understand the unique properties of these fully conjugated macrocycles. View details for DOI 10.1371/journal.ppat.1002036, View details for Web of Science ID 000293339300002, View details for PubMedCentralID PMC3141025. This study introduces a technique for the rapid profiling and quantitation of N- and O-glycans on cell membranes using membrane enrichment and nanoflow liquid chromatography/mass spectrometry of native structures. As this special issue testifies, the field of bioorthogonal chemistry is firmly established as a challenging frontier of reaction methodology and an important new instrument for biological discovery. Carolyn Bertozzi, PhD, was one of three scientists to be awarded the 2022 Nobel Prize in Chemistry earlier today for the development of click chemistry and bio-orthogonal chemistry. To understand the adaptation of Mycobacterium tuberculosis to the intracellular environment, we used comprehensive metabolite profiling to identify the biochemical pathways utilized during growth on cholesterol, a critical carbon source during chronic infection. Natural mucins are densely glycosylated O-linked glycoproteins that serve numerous functions on cell surfaces. Proteasome inhibition leads to accumulation of cytosolic Nrf1, which is then processed to form the active transcription factor. Here we show that the cytosolic enzyme N-glycanase 1 (NGLY1, the human PNGase) is essential for Nrf1 activation in response to proteasome inhibition. Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. Screening of a saturation mutagenesis library of the E. coli methionyl-tRNA synthetase (MetRS) led to the discovery of three MetRS mutants capable of incorporating the long-chain amino acid azidonorleucine into recombinant proteins with modest efficiency. They write new content and verify and edit content received from contributors. Our observations are the first reported instance of dehydration resistance provided by a membrane glycolipid. View details for DOI 10.1021/jacs.0c07700. We report a method for selective labeling, affinity enrichment, and identification of cell-surface glycoproteins. Bertozzi is the only female scientist to have been awarded a science Nobel prize this year, after an all-male line-up in 2021. Using a fluorescent marker tagged to the ring molecule, Bertozzi was able to track the ring compound as it bound to the glycan, in this way developing a map of the glycan location. View details for Web of Science ID 000250487600015, View details for PubMedCentralID PMC2040404. 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 glycosylated polymers were end-functionalized with lipid groups and embedded into supported lipid bilayers where they interact with protein receptors in a structure-dependent manner. Inactivation of the conserved steAB genes (cgp_1603-1604) was also found to confer EMB hypersensitivity and cell division defects. 1-68A and a 2-dehydroxy analogue, 1-68Aa, inhibit several purified LpxC orthologues. View details for Web of Science ID 000089664300011, View details for Web of Science ID 000089432300004. Unnatural sialic acids are generated by metabolic conversion of synthetic N-acyl mannosamines and are typically incorporated into cell-surface glycoconjugates. Our findings indicate that glycan valency can set thresholds for cross-linking by lectins. The profile, which comprised 546 proteins, suggests diverse functions of the phagosome and potential connections to secretory processes, toll-like receptor signaling, and autophagy. WebBio BIO Professor Carolyn Bertozzi's research interests span the disciplines of chemistry and biology with an emphasis on studies of cell surface sugars important to human health and disease. Assignment of intact glycan structures to specific protein attachment sites is a critical step towards elucidating the function encoded in the glycome. The importance and complexity associated with the totality of glycan structures, i.e. View details for Web of Science ID 000222420300014. Mucin-selective proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of mucin domain structure and function. View details for Web of Science ID 000222612600032. Methods for directing the cell surface expression of novel protein-based and oligosaccharide-based epitopes are stimulating new directions in biotechnology and biomedical research. Monomeric sialyl Lewis(X) (sLe(x)) and sLe(x)-like oligosaccharides are minimal structures capable of supporting selectin binding in vitro. The d-alanine analogues were specifically incorporated into nascent PG of the intracellular pathogen Listeria monocytogenes both in vitro and during macrophage infection. Analysis of the genomes of M. tuberculosis, M. leprae, M. smegmatis, and M. avium has revealed a large family of genes homologous to known sulfotransferases. DMN-Tre labeling was detected within minutes and was inhibited by heat killing of mycobacteria. Two approaches that emphasize developing selective methods to dissect, modify, and control receptor-ligand interactions at the cellular interface are discussed. The phosphine-luciferin probe is therefore poised for many applications in real-time imaging in cells and whole animals. View details for DOI 10.1074/jbc.M405709200, View details for Web of Science ID 000223791500101, View details for Web of Science ID 000225338800003. We synthesized a series of GPI-protein analogues bearing modified anchor structures that were designed to dissect the contribution of various glycan components to the GPI-protein's membrane behavior. View details for Web of Science ID 000182331800019. Chemical biotinylation followed by enrichment and mass spectrometry led to the identification of glycoproteins that were found at elevated levels or uniquely in cancerous prostate tissue. In this paper, an efficient enzyme kinetics assay for Stf0 using electrospray ionization (ESI) mass spectrometry is presented. On the basis of these results, we propose possible pathways for 6-sulfo sialyl Lewis x biosynthesis and suggest that sulfation may be an early committed step. We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases. Jolly, A. L., Agarwal, P., Metruccio, M. M., Spiciarich, D. R., Evans, D. J., Bertozzi, C. R., Fleiszig, S. M. Visualization of mycobacterial membrane dynamics in live cells. Mounting evidence indicates that the modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc), the only mammalian glycan found on nuclear and cytoplasmic proteins, helps regulate T cell activation. The controlled addition of structurally defined components to live cell membranes can facilitate the molecular level analysis of cell surface phenomena. Type I sulfatases require an unusual co- or post-translational modification for their activity in hydrolyzing sulfate esters. We demonstrate that gna1Delta strains require a GlcNAc supplement and that expression plasmids containing both exogenous components of the salvage pathway, GlcNAc transporter NGT1 from Candida albicans and GlcNAc kinase NAGK from Homo sapiens, are required for rescue in this context. Membrane-proximal N-linked glycosylation was critical for maintaining the ligand dependence of the receptor. View details for DOI 10.1007/s00216-016-9934-9, View details for Web of Science ID 000391364200021. She is a member of the National Academy of Sciences (2005), the Institute of Medicine (2011), and the National Academy of Inventors (2013). O-Linked -N-acetylgalactosamine (O-GalNAc) glycans constitute a major part of the human glycome. Here, we sought to define if uncharacterized sialidases would provide distinct paradigms in sialic acid biochemistry. In this study, we developed a crosslinking assay, utilizing bioorthogonal probes compatible with carrier protein modification, for probing the protein interactions between COM domains of NRPS enzymes. A 56-member glycopeptide library designed to reflect a diversity of glycan clustering was assayed for substrate activity with ppGalNAcT isoforms using an azido-ELISA. These alkenyl compounds arise from a hydrogen transfer reaction from solvent to the unisolable intermediate, and we postulate that the reaction proceeds via a radical mechanism originating from the strained alkynyl bond that has unusually high radical character. Biochemistry in the context of a living cell or organism is complicated by many variables such as supramolecular organization, cytoplasmic viscosity, and substrate heterogeneity. View details for DOI 10.1073/pnas.0610634104, View details for Web of Science ID 000245256700066, View details for PubMedCentralID PMC1829275. Luchansky, S. J., Goon, S., Bertozzi, C. R. Small molecule inhibitors of mucin-type O-linked glycosylation from a uridine-based library. Sialidases are therefore orchestrators of cellular biology and important therapeutic targets for viral infection. Herein we analyzed the glycopeptide substrate preferences of several ppGalNAcT family members using a library screening approach. However, what is lacking from this biochemical picture is how cells, tissues, and organisms interpret glycan patterns and translate this information into appropriate responses. One of the most abundant is sulfolipid-1 (SL-1), a tetraacyl-sulfotrehalose glycolipid. Zurich, 2011 Tetrahedron Young Investigator Award for Bioorganic and Medicinal Chemistry, 2012 Honorary Doctorate of Science from, 2018 Foreign Member of the Royal Society (ForMemRS), 2020 John J. Carty Award for the Advancement of Science, 2020 F. A. 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. We present the development of NIR fluorogenic azide probes based on the Si-rhodamine scaffold that undergo a fluorescence enhancement of up to 48-fold upon reaction with terminal or strained alkynes. 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. After screening almost 8000 selected clones, we were able to isolate a single specific single chain Fv using two different selection strategies, one of which included elution with tyrosine sulfate. Sulfated forms of sialyl-Le(X) containing Gal-6-SO(4) or GlcNAc-6-SO(4) have been implicated as potential recognition determinants on high endothelial venule ligands for L-selectin. A computational model predicted that these glycoproteins would influence transmembrane receptor spatial organization and function. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. Protein glycosylation is widely recognized as a modulator of protein structure, localization, and cell-cell recognition in multicellular systems. The ketone undergoes highly selective condensation reactions with complementary nucleophiles such as aminooxy and hydrazide groups. To address this shortcoming, we have developed a robust, high-throughput compatible, click chemistry-based approach to identify small molecules that interfere with the palmitoylation of Ras, a high value therapeutic target that is mutated in up to a third of human cancers. There is urgent need for new therapeutic targets and a better understanding of EOC initiation and progression. Here, we use methods that combine collision- and electron-based fragmentation to characterize the number of O-glycosites that are present in O-glycopeptides derived from the OpeRATOR digestion of four known O-glycoproteins. View details for Web of Science ID 000207584000003, View details for PubMedCentralID PMC138933. Using high-performance liquid chromatography, we quantified the degree of accumulation and reversibility upon acidic compartment neutralization in macrophages and observed that accumulation was greater in infected than in uninfected macrophages. Current approaches offer a precision approaching that of genetic control. Mycobacterium tuberculosis, the causative agent of tuberculosis, produces unique sulfated metabolites associated with virulence. She grew up in Lexington, Massachusetts with two sisters, one of which is on the mathematics faculty at the University of California, Los Angeles (UCLA). Fluorescent bioorthogonal smart probes across the visible spectrum will enable sensitive visualization of metabolically labeled molecules in biological systems. Bertozzi is a professor Schilling, B., Goon, S., Samuels, N. M., Gaucher, S. P., Leary, J. The sulfite generated in this reaction is utilized in bacteria and plants for the eventual production of essential biomolecules such as cysteine and coenzyme A. Although genetically encoded tags such as GFP are widely used to monitor discrete proteins, they can cause significant perturbations to a protein's structure and have no direct extension to other classes of biomolecules such as glycans, lipids, nucleic acids and secondary metabolites. 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. 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. The same mineralization technique, when applied to a hydrogel that is less prone to surface hydrolysis, led to distinctly different mineralization patterns, in terms of both the extent of mineralization and the crystallinity of the apatite grown on the hydrogel surface. This bifunctional microelectrode array is demonstrated for the pH monitoring and differentiation of primary T cells and Jurkat T lymphoma cells. Here we applied the bioorthogonal chemical reporter technique for the molecular imaging of mucin-type O-glycans in live C. elegans. 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. View details for DOI 10.1371/journal.pgen.1008284. Moreover, these studies show that to properly exploit the sialic acid biosynthetic pathway for metabolic oligosaccharide engineering in H. ducreyi and possibly other prokaryotes that share similar pathways, precursors based on sialic acid and not mannosamine must be used. Mycobacteria, including persistent pathogens like Mycobacterium tuberculosis, have an unusual membrane structure in which, outside the plasma membrane, a nonfluid hydrophobic fatty acid layer supports a fluid monolayer rich in glycolipids such as trehalose 6,6'-dimycolate (TDM; cord factor). 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. Specific labeling of biomolecules with biochemical and biophysical probes is a central element of proteomics research. 5 '-adenosinephosphosulfate lies at a metabolic branch point in mycobacteria. By analyzing the time and temperature dependencies of formation and transformation we find that the energy barriers to formation of the two states differ by only 0.7 kT, but once the high-energy state forms, the barrier to transformation to the low-energy state is 25 kT. Using this approach, femtomole quantities of several targeted peptides were identified in total mammalian cell lysate, while traditional data-dependent methods were unable to identify as many peptides. This system thus constitutes an AND-type molecular logic gate that reports on the simultaneous presence of H(2)O(2) and caspase 8 activity. A., Cheng, E. H., Bertozzi, C. R., Boyce, M. Modulation of Ocular Surface Glycocalyx Barrier Function by a Galectin-3 N-terminal Deletion Mutant and Membrane-Anchored Synthetic Glycopolymers. Beatty, K. E., Williams, M., Carlson, B. L., Swarts, B. M., Warren, R. M., van Helden, P. D., Bertozzi, C. R. Synthesis and Reactivity of Dibenzoselenacycloheptynes. The results also mean that distinguishing stem cells from other mammalian cells may be facilitated by the major difference in the glycosylation of the cell membrane. The synthesis of the azido sugars (ManNAz, GalNAz, GlcNAz or 6AzFuc) or detection reagents (phosphine-FLAG or phosphine-FLAG-His6) can be completed in approximately 1 week. Bacteria are able to adapt to dramatically different microenvironments, but in many organisms, the signaling pathways, transcriptional programs, and downstream physiological changes involved in adaptation are not well-understood. It deftly subverts the bactericidal mechanisms of alveolar macrophages, ultimately inducing granuloma formation and establishing long-term residence in the host. Bertozzis graduate research focused on carbohydrate analog synthesis, intended for biological applications. Proteins bearing this "aldehyde tag" were chemically modified by selective reaction with hydrazide- or aminooxy-functionalized reagents. Here we studied the mechanism of sulfonucleotide reduction by APS reductase from the human pathogen Mycobacterium tuberculosis, using a combination of mass spectrometry and biochemical approaches. To increase the utility of bioaerosol sampling, we present advances in bioaerosol collection and Mtb identification that improve detection yields.A previously described Respiratory Aerosol Sampling Chamber (RASC) protocol, or "RASC-1", was modified to incorporate liquid collection of bioaerosol using a high-flow wet-walled cyclone (RASC-2). Disruption of cysH rendered Mtb auxotrophic for cysteine and methionine, and attenuated virulence in BALB/c and C57BL/6 immunocompetent mice. ADAP's combination of simplicity, sensitivity, broad dynamic range, multiplexability, and use of standard PCR protocols creates new opportunities for the discovery and detection of antibody biomarkers. Our strategy makes use of an alkyne-bearing S-adenosylmethionine (SAM) analogue, which is accepted by the PKMT, SETDB1, as a cofactor, resulting in the enzymatic attachment of a terminal alkyne to its substrate. Control of enzyme activity is achieved using a small molecule to regulate association of the two domains. We have found that TDM monolayers, in stark contrast to phospholipid membranes, can be dehydrated and rehydrated without loss of integrity, as assessed by fluidity and protein binding. Glycosylation is a prevalent, yet heterogeneous modification with a broad range of implications in molecular biology. Recent advances in our understanding of SL-1 biosynthesis will help elucidate the role of this curious metabolite in M. tb infection. Termed isotopic signature transfer and mass pattern prediction (IsoStamp), the technique exploits the perturbing effects of a dibrominated chemical tag on a peptide's mass envelope, which can be detected with high sensitivity and fidelity using a computational method. The ketone group within the levulinoyl side chain of SiaLev was then used as a chemical handle for detection using a biotin probe. In both leukocyte populations, the main proteins labeled were identified as different CD45 isoforms. This was confirmed by enzymatic assay of the partially purified enzyme with unnatural substrates. Carolyn Bertozzi (Image credit: American Chemical Society) [8] Since 2021 she has been a member of the Accademia dei Lincei. Technologies for introducing molecules into living cells are vital for probing the physical properties and biochemical interactions that govern the cell's behavior. Employing the Huisgen 1,3-dipolar cycloaddition of azides and alkynes, we examined crosslinking of cognate NRPS modules within the tyrocidine pathway and demonstrated the sensitivity of our panel of crosslinking probes toward the selective protein interactions of compatible COM domains. View details for Web of Science ID 000227627800041. Using RAFT polymerization, we synthesized well-defined glycopolymers (GPs) functionalized with galectin-binding glycans along the backbone, a lipid group on one end and a fluorophore on the other. 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. In IsoTaG, metabolic labeling of the glycoproteome is combined with (i) chemical enrichment and isotopic recoding of glycopeptides to select peptides for targeted glycoproteomics using directed MS and (ii) mass-independent assignment of intact glycopeptides. Enlightened by our proteomic data, we performed further experiments to show that only the LAM from M. tuberculosis inhibits accumulation of autophagic vacuoles in the macrophage, suggesting a new function for this virulence-associated lipid. O-linked -N-acetylglucosamine (O-GlcNAc) is a reversible posttranslational modification found on hundreds of nuclear and cytoplasmic proteins in higher eukaryotes. In the paper, Dr. Bertozzi and her team described a new method of engineering an antibody to shuttle a targeted extracellular View details for DOI 10.1074/jbc.M510520200, View details for Web of Science ID 000235426200035. The optimal configuration of sulfate esters on the N-acetyllactosamine (Galbeta1-->4GlcNAc) core of sulfosialyl-Le(X), however, remains unsettled. View details for DOI 10.1073/pnas.1222041110, View details for Web of Science ID 000322771100029, View details for PubMedCentralID PMC3740907. WebCarolyn R. Bertozzi. View details for DOI 10.1371/journal.pone.0242049. In addition, the future of synthetic glycopeptides and glycoproteins as therapeutics is discussed. View details for Web of Science ID 000240465200023, View details for PubMedCentralID PMC3233198. Genes involved in cell signaling, extracellular matrix remodeling, inflammation, angiogenesis and hypoxia were all activated in cells on the collagen-GAG mesh. CysQ is a 3'-phosphoadenosine-5'-phosphatase that dephosphorylates intermediates from the sulfate assimilation pathway of Mycobacterium tuberculosis (Mtb). Subsequently, the embryos were reacted with fluorophore conjugates by means of copper-free click chemistry, enabling the visualization of glycans in vivo at subcellular resolution during development. Mauris, J., Mantelli, F., Woodward, A. M., Cao, Z., Bertozzi, C. R., Panjwani, N., Godula, K., Argueeso, P. Sulfatase-activated fluorophores for rapid discrimination of mycobacterial species and strains. Mycobacterium tuberculosis (Mtb) has evolved into a highly successful human pathogen. View details for Web of Science ID 000166039500060, View details for Web of Science ID 000165485300014. In vivo, BPA appears to have greater activity than is suggested by its estrogen receptor (ER) binding affinity. View details for DOI 10.1038/NCHEMBIO.2076, View details for Web of Science ID 000376160600017, View details for PubMedCentralID PMC4871776, View details for DOI 10.1021/acscentsci.6b00102, View details for PubMedCentralID PMC4850509. Thus, choice of enrichment strategy has profound implications on experimental outcomes. An intriguing example is Sulfolipid-1 (SL-1), a sulfated glycolipid that has been implicated in Mtb pathogenesis, although no direct role for SL-1 in virulence has been established. Dynamic imaging of proteins in live cells is routinely performed by using genetically encoded reporters, an approach that cannot be extended to other classes of biomolecules such as glycans and lipids. (2001) Glycobiology 11, 11R-18R]. 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. The critical reagent, a substituted cyclooctyne, possesses ring strain and electron-withdrawing fluorine substituents that together promote the [3 + 2] dipolar cycloaddition with azides installed metabolically into biomolecules. Detection of metabolites and post-translational modifications can be achieved using the azide as a bioorthogonal chemical reporter. Glioblastoma multiforme (GBMs) are recurrent lethal brain tumours. Here we study the effects of GlcNAc 2-epimerase expression on sialic acid production in cells. 56Carolyn Bertozzi 12 Bertozzi won the prize for studying the sugar coats of cells. Shieh, P., Hangauer, M. J., Bertozzi, C. R. Probing the Mycobacterial Trehalome with Bioorthogonal Chemistry. Here we explored their effect on corneal surface glycosylation using a metabolic label, tetra-acetylated N-azidoacetylgalactosamine (Ac4GalNAz). Ni bis(dithiolene) probes selectively labeled quadricyclane-modified bovine serum albumin, even in the presence of cell lysate. View details for DOI 10.1074/jbc.M111619200, View details for Web of Science ID 000174400600071. Thus, cell surface ketones are a potential vehicle for a metabolically controlled small-molecule drug delivery system. If the sample volume were reduced to 1 nl, we estimate that the detection limit could be improved to 230 +/- 40 L. monocytogenes cells. Thus, new unbiased methods are needed to find PKMT substrates. The resulting trehalose biosynthesis mutant was unable to proliferate and enter stationary phase unless supplemented with trehalose. Tsai, C., Robinson, P. V., Spencer, C. A., Bertozzi, C. R. Amit, I., Baker, D., Barker, R., Berger, B., Bertozzi, C., Bhatia, S., Biffi, A., Demichelis, F., Doudna, J., Dowdy, S. F., Endy, D., Helmstaedter, M., Junca, H., June, C., Kamb, S., Khvorova, A., Kim, D., Kim, J., Krishnan, Y., Lakadamyali, M., Lappalainen, T., Lewin, S., Liao, J., Loman, N., Lundberg, E., Lynd, L., Martin, C., Mellman, I., Miyawaki, A., Mummery, C., Nelson, K., Paz, J., Peralta-Yahya, P., Picotti, P., Polyak, K., Prather, K., Qin, J., Quake, S., Regev, A., Rogers, J. She later refined the approach to improve its utility in cellular environments, facilitating research into interactions between biomolecules and into disease processes. Experimental data confirmed that electronic perturbation of BARAC's aryl rings has a modest effect on reaction rate, whereas steric hindrance in the transition state can significantly retard the reaction. Chen, X., Wu, P., Rousseas, M., Okawa, D., Gartner, Z., Zettl, A., Bertozzi, C. R. DNA-barcode directed capture and electrochemical metabolic analysis of single mammalian cells on a microelectrode array. Synthetic glycopolymers that emulate cell-surface mucins have been used to elucidate the role of mucin overexpression in cancer. Hotsclaw, C. M., Sogi, K. M., Gilmore, S. A., Scheller, M. W., Leavell, M. D., Bertozzi, C. R., Leary, J. However, their weak binding interactions do not correlate with the high-affinity binding interactions witnessed in vivo. WebProfessor Carolyn Bertozzi's research interests span the disciplines of chemistry and biology with an emphasis on studies of cell surface sugars important to human health and disease. Among her many honours are the Lemelson-MIT Prize (2010), the Arthur C. Cope Award of the American Chemical Society (2017), and the Wolf Prize in Chemistry (2022). View details for DOI 10.1016/j.devcel.2019.04.035. Shieh, P., Dien, V. T., Beahm, B. J., Castellano, J. M., Wyss-Coray, T., Bertozzi, C. R. Isotope-targeted glycoproteomics (IsoTaG): a mass-independent platform for intact N- and O-glycopeptide discovery and analysis. Within mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness. Welch Award in Chemistry (2022); The Dickson Prize in Medicine, University of Pittsburgh (2022); Dr H.P. The strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases agreement clinical! 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