Bradley Webb, PhD

Research Interests

*Currently accepting undergraduate researchers for fall of 2023

• Metabolism
• Protein structure/function
• Cell biology of metabolic enzymes

Description of Research

The enzymes and pathways controlling intermediary metabolism for energy production, nutrient utilization, and biomass synthesis play critical roles in cellular homeostasis. Dysregulated metabolic enzymes and pathways are now considered central to diseases such as cancer, diabetes, and neurodegenerative disorders. We currently have limited knowledge of the spatial and temporal dynamics of metabolic enzymes in cells, which is critical for understanding metabolic flexibility in normal cells and aberrant metabolism in diseases. Research in Webb lab is focused on understanding the cell biology of metabolic enzymes.

Regulation of glucose metabolism in cells

Glycolysis is an ancient metabolic pathway for processing glucose into pyruvate, generating energy as well as anabolic building blocks. Glycolytic enzymes function as highly regulated molecular machines that fine-tune the rate of glucose utilization and are dysregulated as well as mutated in cancer and other diseases. Current projects include determining the regulation and functional significance of filament formation by the glycolytic ‘gate-keeper’ enzyme phosphofructokinase-1 (PFK1), the mechanism and significance of a glycolytic metabolon at the plasma membrane, and significance and molecular mechanism of disease-associated somatic mutations to PFK1.

Lysosome dysregulation in the eye

Lysosomes are membrane-bound organelles found in every eukaryotic cell. Originally identified for their catabolic functions that scavenge metabolic building blocks and rid cells of waste, more recently they have been shown to contribute to trafficking of intracellular vesicles, plasma membrane repair, pathogen degradation, resistance to chemotherapies, and a broad range of homeostatic responses to environmental cues. Lysosomal dysfunction has been linked to disparate diseases, including vision loss. Current projects focus on the role of a transmembrane amino acid transporter in lysosome biology and how its dysregulation causes retinitis pigmentosa.

Students may learn techniques including live-cell and immunofluorescent microscopy; cell culture; protein expression and purification; structure/function analysis; enzymology; electron microscopy.

Publications