研究领域
Chemical Glycobiology, Bionanotechnology
The Bertozzi group studies cell surface interactions that contribute to human health and disease with specific projects in the areas of cancer, inflammation and bacterial infection. We use the techniques of organic synthesis, genetics and biochemistry as tools to study and manipulate complex cellular processes. Much of our research involves cell surface oligosaccharides, biopolymers that contribute to cell surface recognition and cell-cell communication, and that pose challenging synthetic targets. In addition to our work in the chemical biology of glycosylation, we have a program in biomaterials centered at the Lawrence Berkeley National Laboratory.
Three major areas of research in the lab span the disciplines of chemistry and biology. First, we are investigating new strategies for engineering novel chemistry on cell surfaces. We exploit the unnatural substrate tolerance of certain enzymes involved in oligosaccharide biosynthesis for the metabolic incorporation of unnatural sugars into cell surface-bound macromolecules. The cell surface display of unnatural sugars bearing uniquely reactive functional groups allows for chemical remodeling using highly selective condensation reactions. Applications of the technology include targeted gene delivery and anti-tumor diagnostics.
Second, we are studying biological sulfation pathways that serve a regulatory during an inflammatory response in humans and during mycobacterial infection. Using genomics approaches, we have identified genes encoding sulfating enzymes that contribute to inflammation, tumor metastasis and possibly microbial infection. These discoveries have prompted new projects in enzymology and in library design and synthesis for the discovery of leads for drug development. In addition, we are synthesizing sulfated oligosaccharides produced by mycobacterial pathogens in order to elucidate their interactions with the host immune response.
Finally, we are exploring new methods for the synthesis of homogeneous glycoproteins and their mimetics. One approach involves the identification of difficult linkages within a glycoprotein and the substitution of those linkages, where tolerable, with a more facile bond. Other approaches merge the techniques of recombinant expression and metabolic engineering to produce novel glycoprotein structures within biological activity.
Chemical Glycobiology, Bionanotechnology
The Bertozzi group studies cell surface interactions that contribute to human health and disease with specific projects in the areas of cancer, inflammation and bacterial infection. We use the techniques of organic synthesis, genetics and biochemistry as tools to study and manipulate complex cellular processes. Much of our research involves cell surface oligosaccharides, biopolymers that contribute to cell surface recognition and cell-cell communication, and that pose challenging synthetic targets. In addition to our work in the chemical biology of glycosylation, we have a program in biomaterials centered at the Lawrence Berkeley National Laboratory.
Three major areas of research in the lab span the disciplines of chemistry and biology. First, we are investigating new strategies for engineering novel chemistry on cell surfaces. We exploit the unnatural substrate tolerance of certain enzymes involved in oligosaccharide biosynthesis for the metabolic incorporation of unnatural sugars into cell surface-bound macromolecules. The cell surface display of unnatural sugars bearing uniquely reactive functional groups allows for chemical remodeling using highly selective condensation reactions. Applications of the technology include targeted gene delivery and anti-tumor diagnostics.
Second, we are studying biological sulfation pathways that serve a regulatory during an inflammatory response in humans and during mycobacterial infection. Using genomics approaches, we have identified genes encoding sulfating enzymes that contribute to inflammation, tumor metastasis and possibly microbial infection. These discoveries have prompted new projects in enzymology and in library design and synthesis for the discovery of leads for drug development. In addition, we are synthesizing sulfated oligosaccharides produced by mycobacterial pathogens in order to elucidate their interactions with the host immune response.
Finally, we are exploring new methods for the synthesis of homogeneous glycoproteins and their mimetics. One approach involves the identification of difficult linkages within a glycoprotein and the substitution of those linkages, where tolerable, with a more facile bond. Other approaches merge the techniques of recombinant expression and metabolic engineering to produce novel glycoprotein structures within biological activity.
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Jolly, A. L.; Agarwal, P.; Metruccio, M. M.; Spiciarich, D. R.; Evans, D. J.; Bertozzi, C. R.; Fleiszig, S. M. Corneal surface glycosylation is modulated by IL-1R and Pseudomonas aeruginosa challenge but is insufficient for inhibiting bacterial binding. FASEB J. 2017, ASAP.
Ganesan, L.; Shieh, P.; Bertozzi, C. R.; Levental, I.Click-chemistry based high throughput screening platform for modulators of Ras palmitoylation. Sci Rep. 2017, 7, 41147.
Rodriguez-Rivera, F. P.; Zhou, X,; Theriot, J. A. ; Bertozzi, C, R.Visualization of mycobacterial membrane dynamics in live cells. J. Am. Chem. Soc. 2017, ASAP.
Schump, M. D.; Fox, D. M.; Bertozzi, C. R.; Riley, L. W. Subcellular partitioning and intra-macrophage selectivity of antimicrobial compounds against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 2017, ASAP.
Woo, C. M.; Felix, A.; Zhang, L.; Elias, J. E.; Bertozzi, C. R. Isotope-targeted glycoproteomics (IsoTaG) analysis of sialylated N- and O-glycopeptides on an Orbitrap Fusion Tribrid using azido and alkynyl sugars. Anal. Bioanal. Chem. 2017, 409, 579-588.
Palaniappan, K. K.; Bertozzi, C. R. Chemical glycoproteomics. Chem. Rev. 2016, 116, 14277-14306.
Sogi, K. M.; Holsclaw, C. M.; Fragiadakis, G. K.; Nomura, D. K.; Leary, J. A.; Bertozzi, C. R. Biosynthesis and regulation of sulfomenaquinone, a metabolite associated with virulence in Mycobacterium tuberculosis. ACS Infect. Dis. 2016, 2, 800-806.
Zhu, X.; Shieh, P.; Su, M.; Bertozzi, C. R.; Zhang, W. A fluorogenic screening platform enables directed evolution of an alkyne biosynthetic tool. Chem. Commun. (Camb). 2016, 52, 11239-11242.
Xiao, H.; Woods, E. C.; Vukojicic, P.; Bertozzi, C. R. Precision glycocalyx editing as a strategy for cancer immunotherapy. Proc. Natl. Acad. Sci. U.S.A. 2016, 113, 10304-10309.
Bhat, R.; Belardi, B.; Mori, H.; Kuo, P.; Tam, A.; Hines, W. C.; Le, Q. T.; Bertozzi, C. R.; Bissell, M. J. Nuclear repartitioning of galectin-1 by an extracellular glycan switch regulates mammary morphogenesis. Proc. Natl. Acad. Sci. U.S.A. 2016, 113, E4820-E4827.
Robinson, P. V.; Tsai, C. T.; de Groot, A. E.; McKechnie, J. L.; Bertozzi, C. R. Glyco-seek: Ultrasensitive detection of protein-specific glycosylation by proximity ligation polymerase chain reaction. J. Am. Chem. Soc. 2016, 138,, 10722-10725.
Hudak, J. E.; Belardi, B.; Appel, M. J.; Solania, A.; Robinson, P. V.; Bertozzi, C. R. Piperidine-based glycodendrons as protein N-glycan prosthetics. Bioorg. Med. Chem. 2016, S0968-0896, 30383-30292.
Ngo, J. T.; Adams, S. R.; Deerinck, T. J.; Boassa, D.; Rodriguez-Rivera, F.; Palida, S. F.; Bertozzi, C. R.; Ellisman, M. H.; Tsien, R. Y. Click-EM for imaging metabolically tagged nonprotein biomolecules. Nat. Chem. Bio. 2016, 12, 459–465.
Sheta, R.; Woo, C. M.; Roux-Dalvai, F.; Fournier, F.; Bourassa, S.; Droit, A.; Bertozzi, C. R.; Bachvarov, D. A metabolic labeling approach for glycoproteomic analysis reveals altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells. J. Prot. 2016, 145, 91-102.
Lantos, A. B.; Carlevaro, G.; Araoz, B.; Ruiz Diaz, P.; Camara, Mde. L.; Buscaglia, C. A.; Bossi, M.; Yu, H.; Chen, X.; Bertozzi, C. R.; Mucci, J.; Campetella, O. Sialic acid glycobiology unveils Trypanosoma cruzi trypomastigote membrane physiology. PLoS Pathog. 2016, 12, e1005559.
Woo, C. M.; Bertozzi, C R. Isotope targeted glycoproteomics (IsoTaG) to characterize intact, metabolically labeled glycopeptides from complex proteomes. Curr. Protoc. Chem. Biol. 2016, 8, 59-82.
Tsai, C.; Robinson, P. V.; Spencer, C. A.; Bertozzi, C. R. Ultrasensitive antibody detection by agglutination-PCR (ADAP). ACS Cent. Sci. 2016, 2, 139-147.
Freeman, S. A.; Goyette, J.; Furuya, W.; Woods, E. C.; Bertozzi, C. R.; Bergmeier, W.; Hinz, B.; van der Merwe, P. A.; Das, R.; Grinstein, S. Integrins form an expanding diffusional barrier that coordinates phagocytosis. Cell 2016, 164, 128-140.
Woods, E. C.; Yee, N. A.; Shen, J.; Bertozzi, C. R. Glycocalyx engineering with a recycling glycopolymer that increases cell survival in vivo. Angew. Chem. Int. Ed. Engl. 2015, Available online.
Kim, J.; Bertozzi, C. R. A bioorthogonal reaction of N-oxide and boron reagents. Angew. Chem. Int. Ed. Engl. 2015, Available online.
Varki, A.; Cummings, R. D.; Aebi, M.; Packer, N. H.; Seeberger, P. H.; Esko, J. D.; Stanley, P.; Hart, G.; Darvill, A.; Kinoshita, T.; Prestegard, J. J.; Schnaar, R. L.; Freeze, H. H.; Marth, J. D.; Bertozzi, C. R.; Etzler, M. E.; Frank, M. Vliegenthart, J. F.; Lütteke, T.; Perez, S.; Bolton, E.; Rudd, P.; Paulson, J.; Kanehisa, M.; Toukach, P.; Aoki-Kinoshita, K. F.; Dell, A.; Narimatsu, H.; York, W.; Taniguchi, N.; Kornfeld, S. Symbol nomenclature for graphical representations of glycans. Glycobiology 2015, 25, 1323-1324.
Kramer, J. R.; Onoa, B.; Bustamante, C.; Bertozzi, C. R. Chemically tunable mucin chimeras assembled on living cells. Proc. Natl. Acad. Sci. U. S. A. 2015, 112, 12574-12579.
Robinson, P. V.; de Almeida-Escobedo, G.; de Groot, A. E.; McKechnie, J. L.; Bertozzi, C. R. Live-cell labeling of specific protein glycoforms by proximity-enhanced bioorthogonal ligation. J. Am. Chem. Soc. 2015, 137, 10452-10455.
Belardi, B.; Bertozzi, C. R. Chemical lectinology: tools for probing the ligands and dynamics of mammalian lectins in vivo. Chem Biol. 2015, 15, 259-268.
Agarwal, P.; Beahm B. J.; Shieh, P.; Bertozzi, C. R. Systemic fluorescence imaging of zebrafish glycans with bioorthogonal chemistry. Angew. Chem. Int. Ed. Engl. 2015. 54, 11504-11510.
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