Associate Professor of Chemistry and Biochemistry
(on leave for the 2016-17 academic year)
Druckenmiller Hall - 255
Chemical tools to target, alter and understand disease-related sugars
My research focuses on the sugars that coat cells. Sugars cover the surfaces of all of the cells in our bodies, and their structures provide meaningful information about cellular identity. For instance, sugars cover our red blood cells, and their structures are responsible for differentiating between A, B and O blood types. As another example, the structures of sugars on disease-causing bacteria look vastly different from the sugars on human cells. Sugars are thus interesting targets for selective modification and analysis. Since sugars are difficult to study by most conventional methods (e.g. genetics), the use of chemical approaches with small molecules containing chemical handles, in combination with other technologies, is necessary to alter and analyze these biomolecules. The broad goals of the Dube laboratory are to develop and apply chemical approaches to better understand the role of sugars in human disease, and to target unique sugars for therapeutic and diagnostic purposes.
Current work in the Dube laboratory
Recent efforts in the laboratory have focused on the pathogenic bacterium Helicobacter pylori, which is the leading cause of duodenal ulcers and stomach cancer worldwide. Unfortunately, existing antibiotics no longer effectively eradicate H. pylori infection and cure these ailments. The development of new treatments will be greatly aided by insights into the pathogenesis of H. pylori. H. pylori’s ability to cause disease appears to be directly linked to its ability to sugar-coat its proteins: H. pylori's flagellin proteins are heavily glycosylated with the unusual nine-carbon sugar pseudaminic acid, and this modification is absolutely essential for H. pylori to synthesize functional flagella and colonize the host's stomach. Although H. pylori's sugars are linked to pathogenesis and are targets of therapeutic intervention, what is not clear is which of these species are involved in host-pathogen interactions, how they can be harnessed to treat chronic H. pylori infection, and if they can be targeted selectively. We are taking a metabolic labeling-based approach to study H. pylori sugar-coated proteins and to target H. pylori based on its unique sugars. In essence, we are pursuing a series of parallel projects that seek to:
Student research opportunities
Students who conduct research in the Dube lab are exposed to a variety of extremely powerful chemical and biological techniques, including organic synthesis, molecular cloning, protein expression and purification, and bacterial and mammalian cell culture. If you’re interested in conducting research in the Dube lab, please set up an appointment with Professor Dube to discuss this possibility.
K. R. Farnham and D. H. Dube, "A semester-long project-oriented biochemistry laboratory based on Helicobacter pylori urease" Biochem. Mol. Biol. Educ., 2015, 43, 333-340.
V. Tra* and D. H. Dube, "Chemical tools to detect and target Helicobacter pylori's glycoproteins" In Glycoscience: Biology and Medicine, T. Endo, P. Seeberger, G. Hart, C-H Wong, N. Taniguchi, ed., Springer (Japan), 2014.
V. Tra* and D. H. Dube, "Glycans in pathogenic bacteria -- potential for targeted covalent therapeutics and imaging agents," Chem. Commun., 2014, 50, 4659-4673.
K. Champasa*, S. A. Longwell*, A. M. Eldridge, E. A. Stemmler and D. H. Dube, "Targeted identification of glycosylated proteins in the gastric pathogen Helicobacter pylori", Mol. Cell. Proteomics, 2013, 12, 2588-2586.
P. Kaewsapsak*, O. Esonu*, and D. H. Dube, "Recruiting the host's immune system to target Helicobacter pylori's surface glycans", ChemBioChem, 2013, 14, 721-726
S. A. Longwell* and D. H. Dube, "Deciphering the bacterial glycocode: recent advances in bacterial glycoproteomics", Curr. Opin. Chem. Biol., 2013, 17, 41-48
D. H. Dube. "Metabolic labeling of bacterial glycans with chemical reporters." In Bacterial glycomics: Current research, technology, and applications. Twine, S. M., ed. Horizon Scientific Press, Norfolk (UK), 2012
D. H. Dube†, B. Li†, E. J. Greenblatt, S. Nimer, A. K. Raymond* and J. J. Kohler, "A two-hybrid assay to study interactions within the secretory pathway", PLOS One, 2010, 5, e15648. [† These authors contributed equally to this work.]
D. H. Dube, K. Champasa* and B. Wang*, "Chemical tools to discover and target bacterial glycoproteins",Chem. Commun., 2011, 47, 87-101.
P. V. Chang, D. H. Dube and C. R. Bertozzi, "A strategy for the selective imaging of glycans using caged metabolic precursors", J. Am. Chem. Soc., 2010, 132, 9516-9518.
M. B. Koenigs*, E. A. Richardson* and D. H. Dube, "Metabolic profiling of Helicobacter pylori glycosylation",Mol. BioSyst., 2009, 5, 909-912.
D. H. Dube, C. L. De Graffenried and J. J. Kohler, “Regulating cell surface glycosylation with a small-molecule switch”, Meth. Enzymol., 2006, 415, 213-229.
D. H. Dube†, J. A. Prescher†, C. N. Quang* and C. R. Bertozzi, “Probing mucin-type O-linked glycosylation in living animals”, Proc. Nat’l Acad. Sci. USA, 2006, 103, 4819-4824. [†These authors contributed equally to this work.]
D. H. Dube and C. R. Bertozzi, “Glycans in cancer and inflammation: potential for therapeutics and diagnostics”, Nat. Rev. Drug Disc., 2005, 4, 477-488.
J. A. Prescher†, D. H. Dube†, and C. R. Bertozzi, “Chemical remodeling of cell surfaces in living animals”Nature, 2004, 430, 873-877. [†These authors contributed equally to this work.]
D. H. Dube and C. R. Bertozzi, “Metabolic oligosaccharide engineering as a tool for glycobiology”, Curr. Opin. Chem. Biol., 2003, 7, 1-10.
S. J. Luchansky, H. C. Hang, E. Saxon, J. R. Grunwell, C. Yu, D. H. Dube and C. R. Bertozzi, “Constructing azide-labeled cell surfaces using polysaccharide biosynthetic pathways”, Meth. Enzymol., 2003, 362, 249-272.
*indicates undergraduate co-author
When she is not trying to “cure cancer” (as her Mom proudly broadcasts to the world), she spends as much time playing with her kids, staying active, and getting outdoors as possible. On the weekends she’s rock climbing, backpacking, hiking or skiing with her husband and kids. On special occasions, you can find her underwater exploring a coral reef. Danielle is hugely fond of coral reefs, as they were both her first outdoor playground and the first place that she discovered her passion for experimental science.