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.