Danielle Dube (she/her/hers)

Norma L. and Roland G. Ware, Jr. 化学与生物化学教授，化学系系主任

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, 我的教学目标是教我的学生 how to think about chemistry and how they can contribute 以对个人有意义的方式进入这个领域.

我的研究重点是包裹细胞的糖. 糖覆盖在我们身体所有细胞的表面, 它们的结构提供了买球平台细胞身份的有意义的信息. For instance, sugars cover our red blood cells, 它们的结构负责区分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. 因此，糖是选择性修饰和分析的有趣目标. 因为糖很难用最传统的方法来研究.g. genetics), the use of chemical approaches with small molecules containing chemical handles, 与其他技术相结合, 有必要改变和分析这些生物分子吗.

The broad goals of the Dube laboratory are to develop and apply chemical approaches to better understand the role of sugars in human disease, 并针对独特的糖进行治疗和诊断.

Dube实验室的当前工作

实验室最近的工作集中在致病菌上 Helicobacter pylori在世界范围内，它是导致十二指肠溃疡和胃癌的主要原因. 不幸的是，现有的抗生素已不能有效根除 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, 这种修改对于 H. pylori 合成功能性鞭毛并在寄主胃中定植.

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, 如何利用它们来治疗慢性疾病 H. pylori 感染，以及它们是否能被改变以解除细菌的武装. 我们正在采用基于代谢标记的方法进行研究 H. pylori 糖衣蛋白和靶蛋白 H. pylori based on its unique sugars. 从本质上讲，我们正在进行一系列平行的项目，力求:

Structurally characterize H. pylori’s distinctive sugars
探索这些糖在导致疾病中的作用
确定负责其生物合成的基因
Validate H. pylori’s sugars as potential drug targets
创造细菌聚糖生物合成抑制剂
Alter H. pylori'S聚糖包被作为增强免疫识别的手段
Hypersensitize H. pylori 对抗生素通过糖萼扰动

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, 蛋白表达与纯化, 细菌和哺乳动物细胞培养. 如果你有兴趣在杜布实验室做研究的话, 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 聚糖生物合成调节宿主识别和反应." 细胞与感染微生物学前沿, 2024, 14, http://doi.org/10.3389/fcimb.2024.1377077

D. Calles-Garcia and D. H. Dube. “化学生物学工具探测细菌聚糖." 化学生物学的最新观点, 2024, 80, http://doi.org/10.1016/j.cbpa.2024.102453

I. Quintana,* A. Paul, A. Chowdhury,* K. D. Moulton, S. S. Kulkarni, and D. H. Dube. "巯基糖苷作为细菌聚糖生物合成的代谢抑制剂." ACS Infectious Diseases., 2023, 9, 2025-2035. http://doi.org/10.1021/acsinfecdis.3c00324

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, http://doi.org/10.1002/ijch.202200050

bacterial_sugars

P. Luong,* A. Ghosh, K. D. Moulton, S. S. Kulkarni, and D. H. Dube. "Synthesis and application of rare deoxy amino L-sugar analogs to probe glycans in pathogenic bacteria." 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. "细菌聚糖生物合成的代谢抑制剂." 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 小鼠体内化学手册:从烧瓶到动物, K. Tanaka, K. Vong eds., Wiley-VCH (Germany), 2020, http://doi.org/10.1002/9783527344406.ch8

T. D. Epstein*†, B. Wu†, K. D. Moulton, M. Yan, D. H. Dube, "Sugar-modified auranofin analogs are potent inhibitors of the gastric pathogen 幽门螺杆菌" ACS传染病, 2019, 5, 1682-1687.

D. H. Dube，“为非理工科学生设计一门药物发现课程” 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, "一个学期的项目导向的生物化学实验室为基础 Helicobacter pylori urease" Biochem. Mol. Biol. Educ., 2015, 43, 333-340.

V. Tra* and D. H. Dube, "用于探测和定位的化学工具 Helicobacter pylori's glycoproteins糖苷科学:生物学和医学，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，“招募宿主的免疫系统作为目标 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. 用化学报告器对细菌聚糖进行代谢标记." In 细菌糖组学:目前的研究、技术和应用. Twine, S. M., ed. 地平线科学出版社，英国诺福克; 2012

D. H. Dube†, B. Li†, E. J. Greenblatt, S. Nimer, A. K. Raymond* and J. J. Kohler, "研究分泌途径内相互作用的双杂交试验", PLOS One, 2010, 5, e15648. [†]这些作者对这项工作贡献相同.]

D. H. Dube, K. Champasa* and B. Wang*，“发现细菌糖蛋白的化学工具”，化学学报. 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, “用小分子开关调节细胞表面糖基化”, 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. [†]这些作者对这项工作贡献相同.]

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，《买球平台》，Nature， 2004, 430, 873-877. [†]这些作者对这项工作贡献相同.]

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D. H. Dube and C. R. Bertozzi, “代谢寡糖工程作为糖生物学的工具”, 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, †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. 我的研究重点是广泛存在的抗生素耐药性问题, 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! 虽然我听说这是一个可怕的“淘汰课程”，但我发现它很吸引人! I was hooked by the problem-solving nature of the field and the ability to make powerful predictions about molecules and their reactivity. 但我也被美丽、优雅和生活的内在规律所吸引. 我无法想象要做出选择. 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, 在那里我可以和优秀的学生一起教学和工作, colleagues, and collaborators.

When I am not trying to “cure cancer” (as my Mom proudly broadcasts to the world), 我花同样多的时间和我的孩子们玩, staying active, and getting outdoors as possible. On the weekends I go rock climbing, backpacking, hiking or skiing with my husband and kids. 在特殊情况下，你可以看到我在水下探索珊瑚礁. 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 Bio东北大学(理学硕士).A. in Biochemistry). 她发展了广泛的微生物学研究， bio化学，免疫学和糖科学技能通过她在 research and bio技术(包括太平洋西北研究基金会，Xoma公司)., 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 Bowdoin 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, 在她承担的无数其他任务中. Outside of the lab, 她喜欢和她的拉布拉多犬道格在海滩上散步, hiking in the Maine mountains, photography with her partner Jeni, 并与许多朋友联系, family, 还有崇拜她的学生(现在的和以前的), and who she adores.

Recent Pictures of the Dube Lab: