Timothy A. Springer

Last updated
Timothy Alan Springer [1]
Born (1948-02-23) February 23, 1948 (age 77) [2]
Fort Benning, Georgia [2]
Education Harvard University (PhD)
University of California, Berkeley (BA) [3]
Known forDiscovery of LFA-1 and other integrins
Awards Robert Koch Prize
Albert Lasker Award for Basic Medical Research
Canada Gairdner International Award
Crafoord Prize
American Society of Hematology Henry M. Stratton Medal
Biophysical Society Founders Award
Protein Society Stein & Moore Award
Scientific career
Fields Immunology
Structural biology
Biophysics
Biochemistry
Institutions Harvard University
Boston Children's Hospital
Dana Farber Cancer Institute
University of Cambridge
MRC Laboratory of Molecular Biology [3]
Thesis Detergent soluble products of HLA  (1976)
Doctoral advisor Jack Strominger [4]
Website https://timothyspringer.org

Timothy "Tim" A. Springer (born February 23, 1948) is an American biochemist, immunologist, and biophysicist known for his foundational work on protein allostery, cell adhesion, vasculature, and immune regulation. He is the Latham Family Professor at Harvard Medical School [5] in the Departments of Pediatrics and of Biological Chemistry and Molecular Pharmacology [5] , and a faculty member in the Program in Cellular and Molecular Medicine and Division of Hematology at the Boston Children’s Hospital (BCH). [6] Springer is best known for discovering the first integrins, LFA-1, and intercellular adhesion molecules (ICAMs), [7] and for elucidating how these cell adhesion molecules function in the immune system. In recent years, his laboratory has expanded to structural and mechanobiological studies of integrins, transforming growth factor β (TGF-β), and synthetic hydrogels designed to enhance organoid fidelity for regenerative medicine and drug discovery.

Contents

Early life and education

Springer was born in Fort Benning, Georgia in 1948 [2] . His father was a physician. [8] Springer attended public high school in California and enrolled at the University of California, Berkeley, majoring in biochemistry and graduating with a BA in 1971. [3] He went on to pursue a PhD under Jack Strominger at Harvard University, completing it in 1976 [4] with a dissertation on membrane-embedded major histocompatibility glycoproteins.

During the Vietnam War, Springer served as a Volunteers in Service to America (VISTA) community development volunteer on the Yomba Shoshone Reservation in Nevada.

Career

After obtaining his PhD, Springer took a postdoctoral position under César Milstein at the University of Cambridge and the MRC Laboratory of Molecular Biology, soon after the development of monoclonal antibody technology. [3] [9] [10]

Springer joined the Medical School faculty in 1977, became an associate professor in 1983 and was appointed Latham Family Professor in 1989. [3] Since 2012, Springer has been a Senior Investigator at the Research Program in Cellular and Molecular Medicine of the Boston Children's Hospital. [3]

Outside of Harvard, Springer was Chief of the Laboratory of Membrane Immunochemistry at the Dana Farber Cancer Institute between 1981 and 1988, and a Senior Investigator at the Immune Disease Institute of Boston from 1988 until its 2012 merge into Boston Children's Hospital. [3] [11]

Springer has played a prominent role in biotechnology. His scientific and entrepreneurial work has contributed to multiple FDA-approved therapies in immunology, oncology, and rare diseases. He founded LeukoSite in 1993, [5] which 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 went public in 1997 and was acquired by Millennium Pharmaceuticals in 1999. [12] He co-founded biotechnology companies Scholar Rock in 2012, [13] Morphic Therapeutic in 2015, [14] Tectonic Therapeutic in 2019, [15] and Seismic Therapeutic in 2022. [16] He was also an early investor in Selecta Biosciences and Editas Medicine. [12]

Springer was a founding investor of Moderna after investing USD$5 million in 2010. [17] He was the company's fourth-largest shareholder and made USD$400 million when the company launched its initial public offering (IPO) in 2018. [18] [19] During the COVID-19 pandemic, Forbes estimated Springer's net worth as USD$1 billion after in share price of biotechnology companies surged. [20]

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, [21] and funded it with a $10 million foundational grant. [12] 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. [22] [23]

Research

Springer began his research career in immunology. He was studying cytotoxic T cells' interaction with antigens, and, since this interaction depends on magnesium, believed a protein in addition to the T-cell receptor is required. [24] He found a monoclonal antibody that binds a new protein prevents cytotoxic T cells interacting with antigens, and named the protein LFA-1. [25] LFA-1 is a heterodimer, meaning it is made of two different protein subunits.

Around the same period, Richard Hynes from the United States and Erkki Ruoslahti from Finland were independently characterizing proteins on the cell surface that helps attach cells to the surrounding extracellular matrix. They discovered fibronectin and a receptor protein to which fibronectin binds. The fibronectin receptor, which Hynes named "integrin", is also a protein heterodimer. [7] [26] Springer found that one of the protein subunits of LFA-1 and Mac-1, a protein heterodimer found on macrophages, has a highly similar DNA sequence to one of the subunits of the fibronectin receptor, suggesting the three proteins belong to the same family of proteins. [27]

Springer's group also discovered ICAM-1, the protein to which LFA-1 binds, and that this interaction is essential for cytotoxic T cells to recognize antigens. [28] [29] His innovative use of monoclonal antibodies in these discoveries [30] paved the way for the development of therapeutic antibodies, known as selective adhesion molecule inhibitors, to treat autoimmune diseases. 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.

In addition, Springer identified the three-step model of leukocyte extravasation (diapedesis), describing how white blood cells move out of the circulatory system towards the site of damage or infection. [31] His research also contributed to understanding TGF-β activation, malaria parasite invasion, and the force-dependent mechanics of von Willebrand factor in hemostasis.

More recently, research at Springer's group has expanded to synthetic, integrin-specific hydrogels and integrin agonists to regulate cell adhesion, polarity, and mechanotransduction in organoid cultures. These defined materials are designed to improve reproducibility, zonulation, and vascularization of human organoids for applications in regenerative medicine, disease modeling, and drug discovery.

Personal life

Springer is a gongshi collector. [32]

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. [33] [34]

Honors and awards

He was a Phi Beta Kappa graduate from the University of California, Berkeley. [8]

References

  1. ↑ "Timothy Alan Springer, Ph.D." Harvard Medical School. October 2019. Archived from the original on April 21, 2023. Retrieved April 21, 2023.
  2. 1 2 3 "Timothy A. Springer". WorldCat Entities. Archived from the original on April 21, 2023. Retrieved April 21, 2023.
  3. 1 2 3 4 5 6 7 8 "CURRICULUM VITAE" (PDF). Immune Disease Institute. Archived from the original (PDF) on April 20, 2017. Retrieved April 17, 2023.
  4. 1 2 Gura, Trisha (September 28, 2022). "IPI co-founder Timothy Springer wins Lasker Award, highlighting key chapter in biology". Institute for Protein Innovation. Archived from the original on April 24, 2023. Retrieved April 24, 2023.
  5. 1 2 3 "Timothy A. Springer, PhD". Harvard Medical School. Archived from the original on June 25, 2023. Retrieved June 25, 2023.
  6. ↑ "Timothy A. Springer". Boston Children's Hospital. Archived from the original on June 25, 2023. Retrieved June 25, 2023.
  7. 1 2 3 "2022 Albert Lasker Basic Medical Research Award". Lasker Foundation. Archived from the original on June 25, 2023. Retrieved June 25, 2023.
  8. 1 2 "Deane Ungerleider to Be Bride Of Timothy A. Springer in May". The New York Times . March 28, 1976. Archived from the original on June 26, 2023. Retrieved June 26, 2023.
  9. ↑ Zamora, Gigi (May 24, 2023). "Billionaire Professor Tim Springer Donates $210 Million To Biomedical Research Nonprofit". Forbes . Archived from the original on June 26, 2023. Retrieved June 26, 2023.
  10. ↑ Dutchen, Stephanie (September 28, 2022). "Timothy Springer Receives Lasker Award". Harvard Medical School. Archived from the original on June 26, 2023. Retrieved June 26, 2023.
  11. ↑ Douglas, Craig (October 1, 2012). "Immune Disease Institute merges into Children's Hospital Boston". Boston Business Journal . Archived from the original on July 8, 2023. Retrieved July 8, 2023.
  12. 1 2 3 Gormley, Brian. "Biotech Entrepreneur Timothy Springer Has Another Act". Wall Street Journal . Archived from the original on July 21, 2017. Retrieved July 21, 2017.
  13. ↑ Saltzman, Jonathan (December 19, 2018). "Cambridge biotech Scholar Rock gets $80m in deal with Gilead". Boston Globe . Archived from the original on April 18, 2023. Retrieved April 18, 2023.
  14. ↑ "Timothy Springer, PhD". Morphic Therapeutic. Archived from the original on June 29, 2023. Retrieved June 29, 2023.
  15. ↑ https://tectonictx.com/wp-content/uploads/2021/04/news_2021-04-15_Tectonic-Therapeutic_Series-A_FINAL-RELEASE.pdf.{{cite web}}: Missing or empty |title= (help)
  16. ↑ https://seismictx.com/seismic-therapeutic-launches-with-101-million-series-a-financing-to-usher-in-a-new-era-of-immunology-drug-development-integrating-machine-learning/.{{cite web}}: Missing or empty |title= (help)
  17. ↑ "Timothy Springer". Forbes. Archived from the original on June 28, 2023. Retrieved June 28, 2023.
  18. ↑ Spalding, Rebecca (December 12, 2018). "A Harvard Professor Made $400 Million in Moderna's Biotech IPO". Bloomberg News . Archived from the original on June 11, 2020. Retrieved June 11, 2020.
  19. ↑ Winck, Ben (April 24, 2020). "A Harvard medical professor is now a billionaire after his early stake in Moderna soared 17,000%". Business Insider . Archived from the original on June 29, 2023. Retrieved June 29, 2023.
  20. ↑ Tognini, Giacomo (May 16, 2020). "Exclusive: Meet The Harvard Professor Who Became A Billionaire Thanks To Coronavirus". Forbes. Archived from the original on June 29, 2023. Retrieved June 29, 2023.
  21. ↑ "Our history". Institute for Protein Innovation. Archived from the original on June 30, 2023. Retrieved June 30, 2023.
  22. ↑ Xiarhos, Kristin (June 20, 2013). "Wu Honored with Springer Professorship". Harvard Medical School. Archived from the original on June 30, 2023. Retrieved June 30, 2023.
  23. ↑ Gigi Zamora (May 24, 2023). "Billionaire Professor Tim Springer Donates $210 Million To Biomedical Research Nonprofit". Forbes.com.
  24. ↑ Ravindran, Sandeep (2022). "QnAs with Richard O. Hynes, Erkki Ruoslahti, and Timothy A. Springer: Winners of the 2022 Albert Lasker Basic Medical Research Award". Proceedings of the National Academy of Sciences of the United States of America . 119 (40) e2213720119. Bibcode:2022PNAS..11913720R. doi: 10.1073/pnas.2213720119 . PMC   9546579 . PMID   36170249.
  25. ↑ Kürzinger, K.; Reynolds, T.; Germain, R. N.; Davignon, D.; Martz, E.; Springer, T. A. (1981). "A novel lymphocyte function-associated antigen (LFA-1): cellular distribution, quantitative expression, and structure" . Journal of Immunology . 127 (2): 596–602. doi: 10.4049/jimmunol.127.2.596 . PMID   6788846. S2CID   42891370.
  26. ↑ Munshi, Hidayatullah G. (2022). "Richard Hynes, Erkki Ruoslahti, and Timothy Springer receive Lasker prize for pioneering work on integrins". Journal of Clinical Investigation . 132 (19) e164374. doi: 10.1172/JCI164374 . PMC   9529252 . PMID   36169028.
  27. ↑ Kishimoto, Takashi K.; O'Connor, Karen; Lee, Alice; Roberts, Thomas M.; Springer, Timothy A. (1987). "Cloning of the β subunit of the leukocyte adhesion proteins: Homology to an extracellular matrix receptor defines a novel supergene family" . Cell . 48 (4): 681–690. doi:10.1016/0092-8674(87)90246-7. PMID   3028646. S2CID   39834662 . Retrieved July 6, 2023.
  28. ↑ Rothlein, R.; Dustin, M. L.; Marlin, S. D.; Springer, T. A. (1986). "A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1" . Journal of Immunology. 137 (4): 1270–1274. doi:10.4049/jimmunol.137.4.1270. PMID   3525675. S2CID   70723.
  29. ↑ Marlin, Steven D.; Springer, Timothy A. (1987). "Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1)" . Cell. 51 (5): 813–819. doi:10.1016/0092-8674(87)90104-8. PMID   3315233. S2CID   24615925 . Retrieved July 8, 2023.
  30. ↑ Springer, . A. (1990). "Adhesion receptors of the immune system" . Nature . 346 (6283): 425–434. Bibcode:1990Natur.346..425S. doi:10.1038/346425a0. PMID   1974032. S2CID   2154164.
  31. ↑ Springer, Timothy A. (1994). "Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm" . Cell. 76 (2): 301–314. doi:10.1016/0092-8674(94)90337-9. PMID   7507411. S2CID   32045369 . Retrieved July 7, 2023.
  32. ↑ Chernick, Karen (January 8, 2021). "Moderna vaccine billionaire Timothy Springer explains his love for Chinese scholar rocks". The Art Newspaper . Archived from the original on June 8, 2023. Retrieved June 8, 2023.
  33. ↑ Kirsner, Scott (July 29, 2022). "This billionaire has quietly driven Boston's biotech industry for decades". Boston Globe. Archived from the original on July 29, 2022. Retrieved June 30, 2023.
  34. ↑ "Chafen Lu, Ph.D." Harvard Medical School. Archived from the original on June 30, 2023. Retrieved June 30, 2023.
  35. ↑ "William B. Coley Award". Cancer Research Institute. Archived from the original on June 28, 2023. Retrieved June 28, 2023.
  36. ↑ "Timothy A. Springer". National Academy of Sciences. Archived from the original on June 28, 2023. Retrieved June 28, 2023.
  37. ↑ "Timothy A. Springer".
  38. ↑ "Timothy Alan Springer". American Academy of Arts and Sciences. 15 May 2023. Archived from the original on June 28, 2023. Retrieved June 28, 2023.
  39. ↑ "The Crafoord Prize in Polyarthritis 2004" (Press release). Royal Swedish Academy of Sciences. January 29, 2004. Archived from the original on July 3, 2023. Retrieved July 3, 2023.
  40. ↑ "Timothy A. Springer". John Simon Guggenheim Memorial Foundation. Archived from the original on July 3, 2023. Retrieved July 3, 2023.
  41. ↑ "Elected Fellows". American Association for the Advancement of Science. Archived from the original on July 3, 2023. Retrieved July 3, 2023.
  42. ↑ Zambon, Kat (November 25, 2013). "AAAS Council Elects 388 New AAAS Fellows". American Association for the Advancement of Science. Archived from the original on July 3, 2023. Retrieved July 3, 2023.
  43. ↑ "AAI-Thermo Fisher Meritorious Career Award Past Recipients". American Association of Immunologists. Archived from the original on July 4, 2023. Retrieved July 4, 2023.
  44. ↑ "Henry M. Stratton Medal Recipients (Formerly Lecture)". American Society of Hematology. Archived from the original on July 4, 2023. Retrieved July 4, 2023.
  45. ↑ "The American Society of Hematology Honors Geraldine P. Schechter, MD, and Timothy Springer, PhD, with 2014 Henry M. Stratton Medal" (Press release). Washington, D.C.: American Society of Hematology. July 22, 2014. Archived from the original on December 28, 2018. Retrieved December 28, 2018.
  46. ↑ "Timothy A. Springer". Gairdner Foundation. 20 October 2019. Archived from the original on July 4, 2023. Retrieved July 4, 2023.
  47. ↑ "Robert Koch Prize 2023 for pioneering work in immunology goes to US and Spanish scientists" (Press release). Robert Koch Foundation. April 17, 2023. Archived from the original on July 4, 2023. Retrieved July 4, 2023.
  48. ↑ "Timothy A. Springer".
  49. ↑ "Timothy A. Springer".
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.