Amara N, Cooper MP, Voronkova MA, Webb BA, Lynch EM, Kollman JM, Ma T, Yu K, Lai Z, Sangaraju D, Kayagaki N, Newton K, Bogyo M, Staben ST, Dixit VM. Selective activation of PFKL suppresses the phagocytic oxidative burst. Cell. 2021. [Epub ahead of print]
Manoli SS, Kisor K, Webb BA, Barber DL. Ethyl Isopropyl Amiloride Decreases Oxidative Phosphorylation and Increases Mitochondrial Fusion in Clonal Untransformed and Cancer Cells. Am J Physiol Cell Physiol. 2021. [Epub ahead of print] PubMed PMID: 34038242.
Webb BA, Aloisio FM, Charafeddine RA, Cook J, Wittmann T, Barber DL. pHLARE: a new biosensor reveals decreased lysosome pH in cancer cells. Mol Biol Cell. 2021 Jan 15;32(2):131-142. PubMed PMID: 33237838;
Lynch EM, Kollman JM, Webb BA. Filament formation by metabolic enzymes-A new twist on regulation. Curr Opin Cell Biol. 2020 Oct; 66:28-33. PubMed PMID: 32417394
Webb BA, Dosey AM, Wittmann T, Kollman JM, Barber DL. The glycolytic enzyme phosphofructokinase-1 assembles into filaments. J Cell Biol. 2017 Aug 7;216(8):2305-2313. PubMed PMID: 28646105.
- JCB Spotlight highlighting the article.
- Selected for Structural Cell Biology 2018 Special Collection.
Webb BA, White KA, Grillo-Hill BK, Schönichen A, Choi C, Barber DL. A Histidine Cluster in the Cytoplasmic Domain of the Na-H Exchanger NHE1 Confers pH-sensitive Phospholipid Binding and Regulates Transporter Activity. J Biol Chem. 2016 Nov 11;291(46):24096-24104. PubMed PMID: 27650500
Webb BA, Forouhar F, Szu FE, Seetharaman J, Tong L, Barber DL. Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations. Nature. 2015 Jul 2;523(7558):111-4. PubMed PMID: 25985179
Grillo-Hill BK, Webb BA, Barber DL. Ratiometric imaging of pH probes. Methods Cell Biol. 2014;123:429-48. PubMed PMID: 24974041.
Choi CH, Webb BA, Chimenti MS, Jacobson MP, Barber DL. pH sensing by FAK-His58 regulates focal adhesion remodeling. J Cell Biol. 2013 Sep 16;202(6):849-59. PubMed PMID: 24043700.
Schönichen A, Webb BA, Jacobson MP, Barber DL. Considering protonation as a posttranslational modification regulating protein structure and function. Annu Rev Biophys. 2013; 42:289-314. PubMed PMID: 23451893.
Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer. 2011 Aug 11;11(9):671-7. PubMed PMID: 21833026.
- Cited over 1000 times.
*Currently accepting undergraduate and graduate researchers for fall of 2021
• 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.