Researcher | Research Overview
Timothy A. Springer discovered with monoclonal antibodies, then cloned and functionally and structurally characterized, many of the adhesion receptors in the immune system. He was the first to demonstrate that lymphocytes and leukocytes had adhesion molecules. His work on these receptors has advanced to characterizing their interactions and allosteric transitions by x-ray crystallography, electron microscopy, and laser tweezers force spectroscopy. His discoveries directly led to the development and FDA approval of Efalizumab, an antibody to LFA-1, and Alefacept, an LFA-3 Fc fusion, both for plaque psoriasis.
Dr. Springer later discovered the three-step paradigm for leukocyte diapedesis: 1) rolling adhesion of leukocytes on the vessel wall through selectins; 2) activation of G protein-coupled receptors on the leukocyte by chemoattractants; and 3) activation of integrin adhesiveness for CAMs on endothelium, which mediates firm adhesion and diapedesis. These discoveries led him to found LeukoSite in 1993. LeukoSite developed three FDA approved therapeutics, including vedolizumab (Entyvio), an antibody to integrin alpha4 beta7 approved for moderate to severe ulcerative colitis and Crohn's disease in 2014. LeukoSite was acquired in 1999 by Millennium Pharmaceuticals.
Dr. Springer’s academic interests now focus on how protein conformational change together with tensile force activates integrins, von Willebrand factor, the transforming growth factor-beta family, and adhesins on malaria sporozoites, and discovering new binding partners. Currently, he is a successful private investor in biotech with seats on five corporate and two non-profit boards. His newest endeavor is the Institute for Protein Innovation, a non-profit to advance entrepreneurship and innovation in protein therapeutics and open-source antibodies and small molecules.
Researcher | Research Background
We’re honored that Dr. Springer has been elected to the National Academy of Medicine for 2023, for his research on receptor-ligand interactions and transmembrane signal transmission that are relevant to immunology, hemostasis, and human disease. Molecules studied include integrins and their ligands, TGF-β, the epidermal growth factor receptor, vaccine targets in malaria, and von Willebrand factor (4750).
Timothy A. Springer is Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Program of Cellular and Molecular Medicine at Boston Children’s Hospital. Dr. Springer graduated from the University of California, Berkeley, and earned a Ph.D. in molecular biology and biochemistry from Harvard University. He is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. In 2004, he was co-recipient of the prestigious Crafoord Prize given by the Royal Swedish Academy of Sciences. Dr. Springer is the recipient of the 2019 Canada Gairdner International Award, recognizing his “seminal discoveries and major scientific contributions constitut[ing] an original and significant achievement in biomedical science.”