Danielle H. Dube
Assistant Professor of Chemistry and Biochemistry
Fall 2008
- Biochemistry (BIO 232)
- Advanced Independent Study and Honors in Biochemistry (BIOC 401)
- Chemical Biology (CHEM 331)
- Chemical Biology (CHEM 331L1)
| Phone | (207) 798-4326 |
| Title | Assistant Professor |
| Department | CHEMISTRY |
| Work Location | 260 Cleaveland Hall |
| ddube@bowdoin.edu |
Education
A.B., Cornell University, 2000
Ph.D., University of California, Berkeley, 2005
Postdoctoral, Stanford University, 2005-2007
Research Interests
Chemical tools to target, alter and understand glycosylation
Glycans, the oligosaccharide chains of sugars attached to many proteins and lipids, cover the surfaces of all cells, where they are crucial for myriad biological functions. In some pathogenic bacteria, glycans are essential for locomotion, and without the appropriate sugars on flagella these bacteria cannot colonize the gastrointestinal tract of their hosts. In pathogenic fungi, glycans are essential components of the cell wall, which provides a primary mode of defense against host immune recognition. Finally, in humans, glycans are responsible for mediating protein-protein interactions, and aberrant protein glycosylation often tracks closely with disease. Glycans are thus interesting targets for selective perturbation and analysis. Because glycans are refractory to study by most conventional methods (e.g. genetics), the use of chemical approaches with small molecule inhibitors and chemical reporters, in combination with other technologies, is necessary to perturb and analyze these biomolecules. The broad goals of the Dube lab are to chemically target unique glycans found on opportunistic pathogens for therapeutic and diagnostic purposes, and to create tools to better understand the role of glycosylation in human disease.
Students who conduct research in the Dube lab will be exposed to a variety of extremely powerful chemical and biological techniques, including organic synthesis, molecular cloning, protein expression and purification, and in vitro kinetics. If you’re interested in conducting research in the Dube lab, please set up an appointment with Professor Dube to discuss this possibility. Current projects in the lab are outlined below.
I.Metabolic incorporation of unnatural sugars into pathogenic bacteria. We are exploiting the pseudaminic acid carbohydrate biosynthetic pathway to incorporate unnatural, chemical reporter-containing variants of this sugar onto Campylobacter jejuni and Helicobacter pylori cell surfaces. The unique display of this chemical reporter on bacterial cells will allow chemical targeting with secondary reagents for therapeutic or diagnostic purposes.
II. Unmasking opportunistic fungal pathogens for immune surveillance. Opportunistic fungal pathogens, such as Candida albicans, have a protective outer mannan coating on their cell walls that masks an underlying, immunoreactive beta-glucan layer (see Fig.). We are developing a general class of fungicides that inhibit the mannosyltransferases responsible for mannan formation; fungal cells exposed to these compounds will have their beta-glucan layer unmasked and will be targeted for immune destruction.
III. Utilizing the Golgi two-hybrid assay to detect the interactions of glycosylated proteins. During her postdoctoral work with Dr. Jennifer Kohler, Prof. Dube developed a two-hybrid assay that is capable of analyzing glycosylated proteins. We will use this assay to study glycoproteins of interest, in particular those associated with human diseases.
Selected Publications
D. H. Dube, E. J. Greenblatt, M. K. Raymond*, D. Sengupta and J. J. Kohler, “Development of a two-hybrid assay capable of analyzing glycosylated proteins”, In prep.
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
Danielle’s other interests
When she is not trying to “cure cancer” (as her Mom proudly broadcasts to the world), she spends as much time playing outdoors as possible. You can often find her rock climbing, backpacking, skiing, or running, all on the same day. 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 science.
Danielle and Callie at Acadia National Park