VWF

One new area of research in the lab is von Willebrand factor and mutations that cause the important bleeding diathesis, von Willebrand disease. We are pursuing single molecule experiments, functional assays, electron microscopy, and crystallography to understand the complex mechanobiology of VWF, which is the largest soluble protein in the body and functions as a shear sensor in the vasculature to arrest arteriolar bleeding. The conformation of VWF, its binding to ligands on the vessel wall and on platelets, and its cleavage by ADAMTS13 are regulated by shear.

Recent Publications

2025

Watson, S. M., Harvey, E. P., Pishesha, N., Ploegh, H. L. & Springer, T. A. Nanobodies targeting EGFR provide insight into conformations stabilized by glioblastoma mutations. The Journal of biological chemistry 110374 (2025) doi:10.1016/j.jbc.2025.110374.
Watson, S. M., Harvey, E. P., Pishesha, N., Ploegh, H. L. & Springer, T. A. Nanobodies targeting EGFR provide insight into conformations stabilized by glioblastoma mutations. The Journal of biological chemistry 110374 (2025) doi:10.1016/j.jbc.2025.110374.
Wang, X. et al. De novo design of integrin α5β1 modulating proteins to enhance biomaterial properties. Adv Mater (2025) doi:10.1002/adma.202500872.
Wang, X. et al. De novo design of integrin α5β1 modulating proteins to enhance biomaterial properties. Adv Mater (2025) doi:10.1002/adma.202500872.

2024

Li, J. et al. Ligand binding initiates single-molecule integrin conformational activation. Cell 187, 2990–3005.e17 (2024).
Li, J. et al. Ligand binding initiates single-molecule integrin conformational activation. Cell 187, 2990–3005.e17 (2024).

2023

Roy, A. et al. De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8. Nat Commun 14, 5660 (2023).
Roy, A. et al. De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8. Nat Commun 14, 5660 (2023).

2022

Jo, M. H. et al. Single-molecule characterization of subtype-specific β1 integrin mechanics. Nat Commun 13, 7471 (2022).
Jo, M. H. et al. Single-molecule characterization of subtype-specific β1 integrin mechanics. Nat Commun 13, 7471 (2022).
Lin, F.-Y. et al. A general chemical principle for creating closure-stabilizing integrin inhibitors. Cell 185, 3533–3550.e27 (2022).
Lin, F.-Y. et al. A general chemical principle for creating closure-stabilizing integrin inhibitors. Cell 185, 3533–3550.e27 (2022).
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VWF Researchers