Immunology Faculty Member - Timothy Springer, PhD

Timothy Springer, PhD

Boston Children's Hospital
3 Blackfan Circle, CLSB, Rm 3103

Boston, MA 02115
Tel: 617-713-8200
Fax: 617-713-8232
Email: springer@crystal.harvard.edu



We work on receptor-ligand interactions, signal transmission across membranes, and regulation by TGF-β of immune responses and role of TGF-β in immuno-oncology. I have a new focus on developing therapeutics for auto-immune diseases and cancer, with strong support from a new non-profit I recently started, the Institute for Protein Innovation. It has a large library of synthetic human antibodies displayed on yeast, enabling selection of antibodies that cross-react between mouse and human targets and rapid translation from mouse models of disease to human therapeutics. Students find my lab fascinating because of the wide range of techniques we use to answer immunological questions, ranging from mechanistic studies to production of knockout mice and in vivo studies. My laboratory has discovered and elucidated the mechanisms of action of many important adhesion molecules of the immune system, including integrins, ICAMs, CD2, and LFA-3, and the chemokine SDF-1 and its receptor CXCR4. Many of my discoveries have been made into drugs. Companies I have founded have brought multiple drugs to market including Entyvio (Vedolizumab), an antibody to integrin alpha4 beta7 that is approved for treatment of ulcerative colitis and Crohns disease.



Last Update: 6/18/2018



Publications

Qin, Y., Garrison, B. S., Ma, W., Wang, R., Jiang, A., Bialas, A., Mistry, M., Bronson, R. T., Santoro, D., Franco, C., Stevens, B., Rossi, D. J., Lu, C., and Springer, T. A. (2018) A Milieu Molecule for TGF-β Required for Microglia Function in the Nervous System. Cell, https://doi.org/10.1016/j.cell.2018.05.027

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 reports 22, 1903-1912
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., Tani, T., Mayor, S., Waterman, C. M., and Springer, T. A. (2017) Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration.
Nature communications 8, 2047

Hinck, A. P., Mueller, T. D., and Springer, T. A. (2016) Structural Biology and Evolution of the TGF-β Family. Cold Spring Harb. Perspect. Biol. 8

Wang, R., Zhu, J., Dong, X., Shi, M., Lu, C., and Springer, T. A. (2012) GARP regulates the bioavailability and activation of TGF-β. Mol. Biol. Cell 23, 1129-1139

Springer, T. A., and Dustin, M. L. (2012) Integrin inside-out signaling and the immunological synapse.
Curr. Opin. Cell Biol. 24, 107-115
Song, G., Koksal, A. C., Lu, C., and Springer, T. A. (2012) Shape change in the receptor for gliding motility in plasmodium sporozoites.
Proc. Natl. Acad. Sci. U. S. A. 109, 21420-21425



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of Harvard College