提摩西·A·斯普林格1948—

Springer is best known for discovering the first cell adhesion molecules of the immune system, the first relationships among integrins—between LFA-1 and Mac-1—and the three-step model for leukocyte emigration from the vasculature. He is also known for entrepreneurship while continuing to run an NIH-funded laboratory, for founding the Institute for Protein Innovation, and for training students and postdoctoral fellows, two of whom are in the National Academy of Sciences. In recent years, his laboratory has focused on structural and mechanobiological studies of integrins, transforming growth factor β (TGF-β), and synthetic scaffolds to zonulate organoids for regenerative medicine..

Early life and education

Springer was born in Fort Benning, Georgia, in 1948. His father was a family physician. Springer attended public high school in Sacramento, California. In 1966, he enrolled at Yale University. After his freshman year, he dropped out and served as a Volunteers in Service to America (VISTA) volunteer. He did community development on the Yomba Shoshone Reservation in Nevada, including getting a road paved so children did not have to live away from home to attend high school. He then enrolled at the University of California, Berkeley, majoring in biochemistry and graduating with a BA in 1971. He went on to pursue a PhD under Jack Strominger at Harvard University, completing it in 1976.

Career and research

Springer then pursued postdoctoral work on antigen-specific T lymphocyte helper factors at the University of Cambridge. Within six months, Springer failed to replicate key experiments and discovered fraudulent work, followed by a retraction. He switched to work under César Milstein at the University of Cambridge and the MRC Laboratory of Molecular Biology, soon after the development of monoclonal antibody technology. Milstein personally taught Springer how to make monoclonal antibodies, and with his first set of hybridomas in hand, Springer returned to the United States after another six months.

Before his postdoc, Springer was offered a position as Assistant Professor at Harvard Medical School by Baruj Benacerraf, the Chair of Pathology, and joined that department in 1977. He was recruited to the Dana–Farber Cancer Institute in 1981 after Benacerraf became its President, as Chief of the Laboratory of Membrane Immunochemistry, and was promoted to Associate Professor in 1983. In 1988, Springer was recruited by Fred Rosen to move his lab to and become Vice President of the Center for Blood Research. He was involved in planning its new space in the Warren Alpert Building and recruiting faculty. These included Ulrich von Andrian, Jose Carlos Gutierrez-Ramos, Rick van Etten, Anjana Rao, Denisa Wagner, and Judy Lieberman. Later, he led searches that recruited Sun Hur, Wesley Wong, and Hao Wu. Four of these recruits were subsequently elected to the National Academy of Sciences. Springer became the Latham Family Professor in 1989. In 2012, the Center for Blood Research, which had changed its name to the Immune Disease Institute, merged with Boston Children's Hospital and became the Program in Cellular and Molecular Medicine of Boston Children's Hospital.

Adhesion molecules of the immune system

Springer began his research career in immunology by studying the molecular basis for cellular immunity using as an example the interaction of cytotoxic T lymphocytes with antigen-bearing target cells. None of the molecules involved in this interaction had yet been defined, including the long postulated antigen-specific T cell receptor. However, it was known that Mg2+ was required for immune cell-cell interactions, and that interaction between fibroblasts and the extracellular matrix was similarly Mg2+-dependent. Postulating that adhesion receptors were likely to be similar to antibodies and were unlikely to require magnesium, Springer hypothesized that other molecules must be required for antigen-specific interactions. He immunized animals with cytotoxic T lymphocytes and screened for monoclonal antibodies that blocked antigen-specific killing. Using this functional assay, his laboratory identified a set of lymphocyte function-associated (LFA) antigens required for cytotoxic T-cell-mediated killing and other T cell-dependent responses, including LFA-1 (CD11a/CD18), LFA-2 (CD2), and LFA-3 (CD58).

Springer's group then identified ICAM-1 as a ligand for LFA-1, demonstrating that this interaction is required for efficient antigen recognition by cytotoxic T cells, and later discovered ICAM-2 (CD102) and ICAM-3 (CD50), which have two to five immunoglobulin (Ig)-like domains and comprise a subfamily of the Ig superfamily.

Philanthropy

In 2017, Springer founded the 501(c)(3) organization Institute for Protein Innovation, which advances open antibody and protein tools for the scientific community, and funded it with a $10 million foundational grant. He also serves on the Board of Trustees of the Marine Biological Laboratory (MBL).

Springer has endowed professorships at Harvard Medical School, Boston Children's Hospital, and Berkeley.

Personal life

Springer is a gongshi collector.

Springer is married to Chafen Lu, a former assistant professor at Harvard Medical School and an alumnus of his lab. He has five children, three from his first marriage.

Honors and awards

• American Heart Association Basic Research Prize (1993)
• William B. Coley Award for Distinguished Research in Basic and Tumor Immunology (1995)
• Member of the National Academy of Sciences (1996)
• Member of the National Academy of Medicine (2023)
• Fellow of the American Academy of Arts and Sciences (2001)
• Crafoord Prize in Polyarthritis (2004)
• Guggenheim Fellowship (2004)
• Fellow of the American Association for the Advancement of Science (2013)

AAI-Life Technologies Meritorious Career Award (now AAI-Thermo Fisher Meritorious Career Award), American Association of Immunologists (2014)

• Henry M. Stratton Medal, American Society of Hematology (2014)
• Canada Gairdner International Award (2019)
• Albert Lasker Award for Basic Medical Research (2022)
• Robert Koch Prize (2023)
• Biophysical Society Founders Award (2022)
• The Protein Society Stein & Moore Award (2025)
• Fellow of the National Academy of Inventors (2025)
• Included in Forbes’ 250: America’s Greatest Innovators list (2026)

Selected to receive the American Society for Biochemistry and Molecular Biology’s Bert and Natalie Vallee Award in Biomedical Science (2027)

He was a Phi Beta Kappa graduate from the University of California, Berkeley.