Danielle Dube

Danielle Dube (she/her/hers)

Norma L. and Roland G. Ware, Jr. Professor of Chemistry and Biochemistry, Chair of the Chemistry Department

I am a chemical biologist who seeks to develop and apply chemical tools to ease the study of sugars that coat the surface of disease-causing bacteria. I teach classes in biochemistry, chemical biology, general chemistry, and drug discovery, and my pedagogical goals are to teach my students how to think about chemistry and how they can contribute to the field in ways that are personally meaningful.

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 altered to disarm the bacteria. 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
Create inhibitors of bacterial glycan biosynthesis
Alter H. pylori's glycan coat as a means to enhance immune recognition
Hypersensitize H. pylori to antibiotics via glycocalyx perturbation

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. A. Barrett, F. J. Kassama, W. Surks, A. Mulholland, K. D. Moulton, and D. H. Dube. "Helicobacter pylori glycan biosynthesis modulates host recognition and response." Fronteirs in Cellular and Infection Microbiology, 2024, 14,

D. Calles-Garcia and D. H. Dube. "Chemical biology tools to probe bacterial glycans." Current Opinion in Chemical Biology, 2024, 80,

I. Quintana,* A. Paul, A. Chowdhury,* K. D. Moulton, S. S. Kulkarni, and D. H. Dube. "." ACS Infectious Diseases., 2023, 9, 2025-2035.

K. Barrett* and D. H. Dube. "Chemical tools to study bacterial glycans: a tale from discovery of glycooproteins to disruption of their function." Israel J. Chem., 2022,

bacterial_sugars

P. Luong,* A. Ghosh, K. D. Moulton, S. S. Kulkarni, and D. H. Dube. "." ACS Infectious Diseases., 2022, 8, 889-900.

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P. Luong* and D. H. Dube. "Dismantling the bacterial glycocalyx: chemical tools to probe, perturb, and image bacterial glycans." Bioorg. Med. Chem., 2021, 42, 116268.

K. D. Moulton, A. P. Adewale*, H. A. Carol*, S. A. Mikami*, and D. H. Dube. "Metabolic glycan labeling-based screen to identify bacterial glycosylation genes." ACS Infectious Diseases, 2020, 6, 3247-3259.

D. A. Williams*†, K. Pradhan†, A. Paul, I. R. Olin*, O. T. Tuck*, K. D. Moulton, S. S. Kulkarni, and D. H. Dube. "." Chemical Science, 2020, 11, 1761-1774.

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D. H. Dube, D. A. Williams*, "Metabolic glycan engineering in live animals: using bioorthogonal chemistry to alter cell surface glycans." In Handbook of in vivo chemistry in mice: from flask to animal, K. Tanaka, K. Vong eds., Wiley-VCH (Germany), 2020,

T. D. Epstein*†, B. Wu†, K. D. Moulton, M. Yan, D. H. Dube, "Sugar-modified auranofin analogs are potent inhibitors of the gastric pathogen Helicobacter pylori" ACS Infectious Diseases, 2019, 5, 1682-1687.

D. H. Dube, "Design of a drug discovery course for non-science majors" Biochem. Mol. Biol. Educ., 2018, 46, 327-335.

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, "" Biochem. Mol. Biol. Educ., 2015, 43, 333-340.

V. Tra* and D. H. Dube, "" 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.

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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 . 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, "", 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, “”, 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, “”, 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.]

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D. H. Dube and C. R. Bertozzi, “”, 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, “”, Meth. Enzymol., 2003, 362, 249-272.

*indicates undergraduate co-author, †These authors contributed equally to this work.

Danielle Dube

Danielle Dube: I spent my formative years in Aberdeen, NJ before attending Cornell University (B.A. in Biology), earning my Ph.D. in Chemistry under the supervision of Carolyn Bertozzi at University of California, Berkeley, and working with Jennifer Kohler at Stanford University as a postdoctoral scholar.

I love thinking about how we can use chemistry to address pressing problems related to human health and disease. My research focuses on the widespread problem of antibiotic resistance, and my research students and I seek to understand how disease-causing bacteria can be inactivated based on their distinctive sugar coating. My path to this work was not premeditated: I was a biology major in college and I thought I wanted to be a doctor. Then, my plans were derailed by an unexpected surprise in my sophomore year: I took organic chemistry. And I loved it! Though I had heard it was a scary “weed-out course,” I found it riveting! I was hooked by the problem-solving nature of the field and the ability to make powerful predictions about molecules and their reactivity. But I was also drawn to the beauty, elegance, and inner-workings of life. I couldn’t imagine having to choose. I was introduced to biochemistry & chemical biology – the intersection of these fields – and realized I didn’t have to choose. Thus, my life-long journey toward using chemistry to address biological questions and problems had begun. That brings us to today, where I get to teach and work with incredible students, colleagues, and collaborators.

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 with her family

Karen Moulton, lab manager

Karen Moulton: Karen Moulton hails from Brandon, VT and received her training at Macalester College (B.A. in Biology) and Northeastern University (M.A. in Biochemistry). She has developed a wide range of microbiology, biochemistry, immunology and glycoscience skills through her work in research and biotechnology(including at the Pacific Northwest Research Foundation, Xoma Corp., and Children’s Hospital of Oakland Research Institute); at the University of Southern Maine she worked with Monroe Duboise in Applied Medical Sciences graduate program in Virology and Electron Microscopy, and at 黑料吃瓜网爆网站 College working with Danielle Dube in the Department of Chemistry & Biochemistry.

Karen serves as lab manager of the Dube lab and helps keep things running smoothly by offering pro-tips, logistical suggestions, thoughtful insights, guiding questions, and encouragement, among the million other tasks she undertakes. Outside of the lab, she enjoys walking on the beach with her labradoodle Dug, hiking in the Maine mountains, photography with her partner Jeni, and connecting with the many friends, family, and students (current and former) who adore her, and who she adores.

Recent Pictures of the Dube Lab: