Stanford University
Showing 71-80 of 308 Results
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Jinhong Du
Postdoctoral Scholar, Chemistry
BioFrom chemist to targeted therapy designer, and now biophysicist—I keep pushing across disciplines, hoping every new boundary crossed brings a few unexpected discoveries.
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Justin Du Bois
Henry Dreyfus Professor of Chemistry and Professor, by courtesy, of Chemical and Systems Biology
BioThe Du Bois lab is heavily invested in exploring voltage-gated ion channel function and physiology and the underlying role of specific channels in human pathologies, particularly nociception, epilepsy, and neurodevelopmental disorders. With expertise in chemical synthesis, we have access to a collection of exceptional natural products—tetrodotoxin, saxitoxin, gonyautoxin, batrachotoxin, veratridine, antillatoxin, to name a few—that act as selective modulators of sodium ion channels (NaVs). In addition, we have developed novel molecules as inhibitors and agonists of specific voltage-gated chloride (ClCs) and calcium (CaVs) channel isoforms. As a lab, we are uniquely positioned to advance high-precision chemical tools to interrogate underlying biochemical mechanisms of electrogenesis. Our work in this arena is guided by a number of questions related to the basic functioning of voltage-gated channels in neuronal cells and glia that include: 1) what is the rate at which channels are being made and degraded and is the rate of channel turnover context dependent (i.e., is protein turnover affected by increased neuronal activity, nerve cell damage, etc.); 2) to what extent is channel expression and cellular distribution affected by external factors (pH, inflammatory modulators, injury); 3) how do post-translational protein modifications influence channel function and how are such modifications altered in response to external factors; 4) how do neighboring glia influence channel expression and ion gating. Answers to these types of questions will provide a deeper understanding of the molecular mechanisms by which neuronal cells and tissue respond to external stimuli, stress, and injury. We benefit from the strong interest of others in our work and multiple collaborators at Stanford and at other institutions.
Ion channel function and physiology. We wish to understand the role of individual subtypes of voltage-gated sodium, chloride, and calcium channels in neuronal signaling and how structural changes (i.e., point mutations, post-translational modifications, partner proteins) alter channel function. Our interests include the design, development, and application of chemogenetic technologies for targeting individual channel subtypes and allosteric modulators of select channel isoforms. Our work aims to inform efforts in translational research, as voltage-gated ion channel dysregulation and malfunction underlie a wide range of human diseases and disorders.
Natural products synthesis. We are interested in developing efficient and flexible synthetic routes to natural products that serve as ‘lead’ compounds for advancing high precision pharmacological tools. Most of the targets we are interested in obtaining are not available in sufficient quantities from natural sources, thus necessitating de novo preparation. To streamline the assembly process of these complex molecules, we are challenged to develop, in parallel, new tactics and chemical methods that facilitate C–C, C–N, and C–O bond formation.
Toxin ‘sponge’ proteins. A longstanding collaboration with the Minor lab at UCSF has focused on understanding how certain organisms that ingest dietary toxins such as saxitoxin, tetrodotoxin, and batrachotoxin survive their poisonous effects. This work has resulted in the elucidation of the structures of novel paralytic shellfish-binding proteins (so-called saxiphilins) and the toxin ‘binding code’. Studies are ongoing to integrate saxiphilins into a diagnostic device for measuring toxin concentrations in shellfish and to advance an engineered toxin-binding protein as a countermeasure for paralytic shellfish poisoning.
