The focus of our laboratory
Disulfide bonds play critical roles in a range of cellular processes – from the stabilization of secreted proteins to regulating cellular adhesion and viral fusion. Our multidisciplinary research program addresses how disulfides are generated and isomerized during oxidative protein folding in higher eukaryotes. We exploit a range of techniques including: peptide and protein purification, molecular biology, enzyme kinetics, rapid reaction studies, absorbance and fluorescence spectroscopy, NMR, mass spectrometry, and protein crystallography.
Current directions of our laboratory include:
- Multidomain disulfide bond-forming catalysts of the secretory pathway and extracellular space: the Quiescin-sulfhydryl oxidase (QSOX) family.
- Pathways for disulfide generation in the mitochondrial intermembrane space: including the flavoprotein, augmenter of liver regeneration (ALR), and its co-substrates.
- Developing models of oxidative protein folding pathways: cooperation between QSOX and the protein disulfide isomerases.
- Inhibitors of oxidative folding.
- Disulfide-rich biomaterials.
A complete understanding of oxidative protein folding must combine insights from cell biology with a critical scrutiny of chemical feasibility and kinetic competence.
“Biology cannot ignore chemistry, much as I wish it could”
(John Maynard Smith)