Publications

de Lau, W.B.M., Wijnakker, J., van Son, G.J.F., Krueger, D., Wang, D., Abendroth, M.S., Schreurs, R., Janda, C.Y., van Rijt, F.L.H., Chalopin, B.J.P., et al. (2025). A single-chain derivative of an integrin-activating antibody potentiates organoid growth in Matrigel and collagen hydrogels. Nat Biotechnol In press. PMID: 41152624.

Wang, X., Guillem-Marti, J., Kumar, S., Lee, D.S., Cabrerizo-Aguado, D., Werther, R., Alamo, K.A.E., Zhao, Y.T., Nguyen, A., Kopyeva, I., et al. (2025). De novo design of integrin α5β1 modulating proteins to enhance biomaterial properties. Adv Mater, e2500872. PMID: 40489013.

Watson, S.M., Harvey, E.P., Pishesha, N., Ploegh, H.L., and Springer, T.A. (2025). Nanobodies targeting EGFR provide insight into conformations stabilized by glioblastoma mutations. J Biol Chem 301, 110374. PMID: 40516870.

Li, J., Jo, M.H., Yan, J., Hall, T., Lee, J., Lopez-Sanchez, U., Yan, S., Ha, T., and Springer, T.A. (2024). Ligand binding initiates single-molecule integrin conformational activation. Cell 187, 2990–3005 e2917. PMID: 38772370.

Le, V.Q., Zhao, B., Ramesh, S., Toohey, C., DeCosta, A., Mintseris, J., Liu, X., Gygi, S., and Springer, T.A. (2023). A specialized integrin-binding motif enables proTGF-β2 activation by integrin αVβ6 but not αVβ8. Proc Natl Acad Sci U S A 120, e2304874120. PMID: 37279271.

Roy, A., Shi, L., Chang, A., Dong, X., Fernandez, A., Kraft, J.C., Li, J., Le, V.Q., Winegar, R.V., Cherf, G.M., et al. (2023). De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8. Nat Commun 14, 5660. PMID: 37704610.

Anderson, J.M., Li, J., and Springer, T.A. (2022). Regulation of integrin α5β1 conformational states and intrinsic affinities by metal ions and the ADMIDAS. Mol Biol Cell 33, ar56. PMID: 35108026.

Feng, J., Dong, X., Su, Y., Lu, C., and Springer, T.A. (2022). Monomeric prefusion structure of an extremophile gamete fusogen and stepwise formation of the postfusion trimeric state. Nat Commun13, 4064. PMID: 35831325.

Jiang, A., Qin, Y., and Springer, T.A. (2022). Loss of LRRC33-dependent TGFβ1 activation enhances antitumor immunity and checkpoint blockade therapy. Cancer Immunol Res 10, 453–467. PMID: 35181792.

Jo, M.H., Li, J., Jaumouille, V., Hao, Y., Coppola, J., Yan, J., Waterman, C.M., Springer, T.A., and Ha, T. (2022). Single-molecule characterization of subtype-specific β1 integrin mechanics. Nat Commun 13, 7471. PMID: 36463259.

Lin, F.Y., Li, J., Xie, Y., Zhu, J., Huong Nguyen, T.T., Zhang, Y., Zhu, J., and Springer, T.A. (2022). A general chemical principle for creating closure-stabilizing integrin inhibitors. Cell185, 3533–3550 e3527. PMID: 36113427.

Fu, H., Jiang, Y., Wong, W.P., and Springer, T.A. (2021). Single-molecule imaging of von Willebrand factor reveals tension-dependent self-association. Blood 138, 2425–2434. 10.1182/blood.2021012595. PMC8662069. PMID: 34882208.

Li, J., Yan, J., and Springer, T.A. (2021). Low-affinity integrin states have faster ligand-binding kinetics than the high-affinity state. Elife 10, e73359. PMID: 34854380.

Dong, X., Leksa, N.C., Chhabra, E.S., Arndt, J.W., Lu, Q., Knockenhauer, K.E., Peters, R.T., and Springer, T.A. (2019). The von Willebrand factor D'D3 assembly and structural principles for factor VIII binding and concatemer biogenesis. Blood 133, 1523–1533. PMID: 30642920.

Wang, J., Su, Y., Iacob, R.E., Engen, J.R., and Springer, T.A. (2019). General structural features that regulate integrin affinity revealed by atypical αVβ8. Nat Commun 10, 5481. PMID: 31792290.

Moore, T.I., Aaron, J., Chew, T.L., and Springer, T.A. (2018). Measuring integrin conformational change on the cell surface with super-resolution microscopy. Cell Rep 22, 1903–1912. PMID: 29444440.

Qin, Y., Garrison, B.S., Ma, W., Wang, R., Jiang, A., Li, J., Mistry, M., Bronson, R.T., Santoro, D., Franco, C., et al. (2018). A milieu molecule for TGF-β required for microglia function in the nervous system. Cell 174, 156–171 e116. PMID: 29909984.

Dong, X., Zhao, B., Iacob, R.E., Zhu, J., Koksal, A.C., Lu, C., Engen, J.R., and Springer, T.A. (2017). Force interacts with macromolecular structure in activation of TGF-β. Nature 542, 55–59. 10.1038/nature21035. PMC5586147. PMID: 28117447.

Fu, H., Jiang, Y., Yang, D., Scheiflinger, F., Wong, W.P., and Springer, T.A. (2017). Flow-induced elongation of von Willebrand factor precedes tension-dependent activation. Nat Commun8, 324. PMID: 28831047.

Li, J., Su, Y., Xia, W., Qin, Y., Humphries, M.J., Vestweber, D., Cabanas, C., Lu, C., and Springer, T.A. (2017). Conformational equilibria and intrinsic affinities define integrin activation. EMBO J 36, 629–645. PMID: 28122868.

Li, J., and Springer, T.A. (2017). Integrin extension enables ultrasensitive regulation by cytoskeletal force. Proc Natl Acad Sci U S A 114, 4685–4690. PMID: 28416675.

Nordenfelt, P., Moore, T.I., Mehta, S.B., Kalappurakkal, J.M., Swaminathan, V., Koga, N., Lambert, T.J., Baker, D., Waters, J.C., Oldenbourg, R., et al. (2017). Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration. Nat Commun 8, 2047. PMID: 29229906.

Nordenfelt, P., Elliott, H.L., and Springer, T.A. (2016). Coordinated integrin activation by actin-dependent force during T-cell migration. Nat Commun 7, 13119. PMID: 27721490.

Su, Y., Xia, W., Li, J., Walz, T., Humphries, M.J., Vestweber, D., Cabañas, C., Lu, C., and Springer, T.A. (2016). Relating conformation to function in integrin α5β1. Proc Natl Acad Sci U S A. 113, E3872–3881. PMID: 27317747.

Kim, J., Hudson, N.E., and Springer, T.A. (2015). Force-induced on-rate switching and modulation by mutations in gain-of-function von Willebrand diseases. Proc Natl Acad Sci U S A 112, 4648–4653. PMID: 25810255.

Dong, X., Hudson, N.E., Lu, C., and Springer, T.A. (2014). Structural determinants of integrin β-subunit specificity for latent TGF-β. Nat. Struct. Mol. Biol. 21, 1091–1096. PMID: 25383667.

Springer, T.A. (2014). von Willebrand factor, Jedi knight of the bloodstream. Blood 124, 1412–1425. PMID: 24928861.

Sen, M., Yuki, K., and Springer, T.A. (2013). An internal ligand-bound, metastable state of a leukocyte integrin, αxβ2. J. Cell Biol. 203, 629–642. PMID: 24385486.

Zhu, J., Zhu, J., and Springer, T.A. (2013). Complete integrin headpiece opening in eight steps. J Cell Biol 201, 1053–1068. PMID: 23798730.

Springer, T.A., and Dustin, M.L. (2012). Integrin inside-out signaling and the immunological synapse. Curr. Opin. Cell Biol. 24, 107–115. PMID: 22129583.

Shi, M., Zhu, J., Wang, R., Chen, X., Mi, L., Walz, T., and Springer, T.A. (2011). Latent TGF-β structure and activation. Nature474, 343–349. PMID: 21677751.

Zhou, Y.F., Eng, E.T., Nishida, N., Lu, C., Walz, T., and Springer, T.A. (2011). A pH-regulated dimeric bouquet in the structure of von Willebrand factor. EMBO J 30, 4098–4111. PMID: 21857647.

Zhang, X., Halvorsen, K., Zhang, C.Z., Wong, W.P., and Springer, T.A. (2009). Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor. Science 324, 1330–1334. PMID: 19498171.

Zhu, J., Luo, B.H., Barth, P., Schonbrun, J., Baker, D., and Springer, T.A. (2009). The structure of a receptor with two associating transmembrane domains on the cell surface: integrin αIIbβ3. Mol Cell34, 234–249. PMID: 19394300.

Zhu, J., Luo, B.H., Xiao, T., Zhang, C., Nishida, N., and Springer, T.A. (2008). Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol Cell 32, 849–861. PMID: 19111664.

Luo, B.H., Carman, C.V., and Springer, T.A. (2007). Structural basis of integrin regulation and signaling. Annu Rev Immunol 25, 619–647. PMID: 17201681.

Xiao, T., Takagi, J., Coller, B.S., Wang, J.H., and Springer, T.A. (2004). Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics. Nature 432, 59–67. PMID: 15378069.

Galagan, J.E., Nusbaum, C., Roy, A., Endrizzi, M.G., Macdonald, P., FitzHugh, W., Calvo, S., Engels, R., Smirnov, S., Atnoor, D., et al. (2002). The genome of M. acetivorans reveals extensive metabolic and physiological diversity. Genome Res 12, 532–542. PMID: 11932238.

Takagi, J., Petre, B.M., Walz, T., and Springer, T.A. (2002). Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell 110, 599–511. PMID: 12230977.

Chen, S., and Springer, T.A. (1999). An automatic braking system that stabilizes leukocyte rolling by an increase in selectin bond number with shear. J Cell Biol 144, 185–200. PMID: 9885254.

Ma, Q., Jones, D., Borghesani, P.R., Segal, R.A., Nagasawa, T., Kishimoto, T., Bronson, R.T., and Springer, T.A. (1998). Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci U S A 95, 9448–9453. PMID: 9689100.

Bleul, C.C., Fuhlbrigge, R.C., Casasnovas, J.M., Aiuti, A., and Springer, T.A. (1996). A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 184, 1101–1109. PMID: 9064327.

Bleul, C.C., Farzan, M., Choe, H., Parolin, C., Clark-Lewis, I., Sodroski, J., and Springer, T.A. (1996). The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382, PMID: 8752280.

Springer, T.A., and Cybulsky, M.I. (1995). Traffic signals on endothelium for leukocytes in health, inflammation, and atherosclerosis. In Atherosclerosis and coronary artery disease, V. Fuster, R. Ross, and E.J. Topol, eds. (Lippincott-Raven Publishers), pp. 511–537.

Springer, T.A. (1994). Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell76, 301–314. PMID: 7507411.

Lawrence, M.B., and Springer, T.A. (1991). Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell 65, 859–873. PMID: 1710173.

Springer, T.A. (1990). Adhesion receptors of the immune system. Nature 346, 425–434. PMID: 1974032.

Dustin, M.L., and Springer, T.A. (1989). T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature341, 619–624. PMID: 2477710.

Dustin, M.L., and Springer, T.A. (1988). Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol 107, 321–331. PMID: 3134364.

Sanders, M.E., Makgoba, M.W., Sharrow, S.O., Stephany, D., Springer, T.A., Young, H.A., and Shaw, S. (1988). Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. J Immunol 140, 1401–1407. PMID: 2894392.

Staunton, D.E., Marlin, S.D., Stratowa, C., Dustin, M.L., and Springer, T.A. (1988). Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 52, 925–933. PMID: 3349522.

Anderson, D.C., and Springer, T.A. (1987). Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med 38, 175–194. PMID: 3555290.

Marlin, S.D., and Springer, T.A. (1987). Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell 51, 813–819. PMID: 3315233.

Springer, T.A., Dustin, M.L., Kishimoto, T.K., and Marlin, S.D. (1987). The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol 5, 223–252. PMID: 3109455.

Dustin, M.L., Rothlein, R., Bhan, A.K., Dinarello, C.A., and Springer, T.A. (1986). Induction by IL 1 and interferon-γ: Tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 137, 245–254. PMID: 3086451.

Pober, J.S., Gimbrone, M.A., Jr., Lapierre, L.A., Mendrick, D.L., Fiers, W., Rothlein, R., and Springer, T.A. (1986). Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol 137, 1893–1896. PMID: 3091693.

Rothlein, R., Dustin, M.L., Marlin, S.D., and Springer, T.A. (1986). A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol 137, 1270–1274. PMID: 3525675.

Sanchez-Madrid, F., Nagy, J.A., Robbins, E., Simon, P., and Springer, T.A. (1983). A human leukocyte differentiation antigen family with distinct α-subunits and a common β-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J Exp Med 158, 1785–1803. PMID: 6196430.

Kurzinger, K., Ho, M.K., and Springer, T.A. (1982). Structural homology of a macrophage differentiation antigen and an antigen involved in T-cell-mediated killing. Nature 296, 668–670. PMID: 6175907.

Sanchez-Madrid, F., Krensky, A.M., Ware, C.F., Robbins, E., Strominger, J.L., Burakoff, S.J., and Springer, T.A. (1982). Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci U S A 79, 7489–7493. PMID: 6984191.