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
2018
Qin, Y. et al. A Milieu Molecule for TGF-β Required for Microglia Function in the Nervous System. Cell (2018) doi:10.1016/j.cell.2018.05.027.
Qin, Y. et al. A Milieu Molecule for TGF-β Required for Microglia Function in the Nervous System. Cell (2018) doi:10.1016/j.cell.2018.05.027.
Moore, T. I., Aaron, J., Chew, T.-L. & Springer, T. A. Measuring integrin conformational change on the cell surface with super-resolution microscopy. Cell Reports In Press, (2018).
Moore, T. I., Aaron, J., Chew, T.-L. & Springer, T. A. Measuring integrin conformational change on the cell surface with super-resolution microscopy. Cell Reports In Press, (2018).
2017
Nordenfelt, P. et al. Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration. Nat Commun 8, 2047 (2017).
Nordenfelt, P. et al. Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration. Nat Commun 8, 2047 (2017).
Fu, H. et al. Flow-induced elongation of von Willebrand factor precedes tension-dependent activation. Nat Commun 8, 324 (2017).
Fu, H. et al. Flow-induced elongation of von Willebrand factor precedes tension-dependent activation. Nat Commun 8, 324 (2017).
Li, J. & Springer, T. A. Integrin extension enables ultrasensitive regulation by cytoskeletal force. Proc Natl Acad Sci U S A (2017) doi:10.1073/pnas.1704171114.
Li, J. & Springer, T. A. Integrin extension enables ultrasensitive regulation by cytoskeletal force. Proc Natl Acad Sci U S A (2017) doi:10.1073/pnas.1704171114.
Dong, X. et al. Force interacts with macromolecular structure in activation of TGF-β. Nature 542, 55–59 (2017).
Dong, X. et al. Force interacts with macromolecular structure in activation of TGF-β. Nature 542, 55–59 (2017).