Danielle Dube

Associate Professor of Chemistry and Biochemistry and Director of Biochemistry Program

Teaching this semester

CHEM 1058. Drug Discovery

The process of drug discovery of medicinal compounds has evolved over millennia, from the shaman’s use of medicinal herbs to the highly evolved techniques of rational design and high-throughput screening used by today’s pharmaceutical industry. Examines past and present approaches to drug discovery, with an emphasis on the natural world as a source of drugs, historical examples of drug discovery, and the experiments undertaken to validate a drug. Encourages students to take initial steps to identify novel therapeutics and to directly compare conventional versus herbal remedies in integrated laboratory exercises. Assumes no background in science. Not open to students who have credit for a chemistry course numbered 1000 (100) or higher.

CHEM 3310. Chemical Biology

The power of organic synthesis has had a tremendous impact on understanding of biological systems. Examines case studies in which synthetically derived small molecules have been used as tools to tease out answers to questions of biological significance. Topics include synthetic strategies that have been used to make derivatives of the major classes of biomolecules (nucleic acids, proteins, carbohydrates, and lipids) and the experimental breakthroughs these molecules have enabled (e.g., polymerase-chain reaction, DNA sequencing, microarray technology). Emphasis on current literature, experimental design, and critical review of manuscripts.

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.

slide

Education

  • A.B., Cornell University, 2000
  • Ph.D , University of California, Berkeley, 2005
  • Postdoctoral, Stanford University, 2005-2007

PDF Curriculum Vitae

The Dube Research Laboratory

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. pyloriH. 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.  Current work in the Dube laboratory 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: 

  • Structurally characterize H. pylori’s distinctive sugars
  • Explore the role of these sugars in causing disease
  • Identify the genes responsible for their biosynthesis
  • Validate H. pylori’s sugars as potential drug targets
  • Develop targeted antibiotics that, like smart-bombs or guided missiles, seek out and react with H. pylori’s sugars, leading to selective destruction of H. pylori cells without destroying beneficial bacteria 

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.

Selected Publications

E. L. Clark*, M. Emmadi, K. L. Krupp*, A. R. Podilapu, J. D. Helble*, S. S. Kulkarni, and D. H. Dube, "Development of rare bacterial monosaccharide analogs for metabolic glycan labeling in pathogenic bacteria" ACS Chem. Biol.2016, 11, 3365-3373.

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

News

Danielle's other interests

When I am not trying to “cure cancer” (as my Mom proudly broadcasts to the world), I spend as much time playing with my kids, staying active, and getting outdoors as possible. On the weekends I go rock climbing, backpacking, hiking or skiing with my husband and kids. On special occasions, you can find me underwater exploring a coral reef. I am hugely fond of coral reefs, as they were both my first outdoor playground and the first place that I discovered my passion for experimental science.

Danielle Dube Family