Timothy A. Springer

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Timothy Alan Springer [1]
Born(1948-02-23)February 23, 1948 [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
Scientific career
Fields Immunology
Structural biology
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]

Timothy "Tim" A. Springer (born February 23, 1948) is an immunologist and the Latham Family Professor at Harvard Medical School. [5] He is also a professor at the Department of Biological Chemistry and Molecular Pharmacology and of the Division of Medical Sciences, [5] and a Senior Investigator at the Research Program in Cellular and Molecular Medicine of the Boston Children's Hospital. [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, Springer's research interest has expanded to malaria, transforming growth factor beta (TGF-β) signaling, and von Willebrand factor. [8] [9]

Contents

Early life and education

Springer was born in 1948 in Fort Benning, Georgia. [2] His father was a physician. [10] Springer attended 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]

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. [3] [11] [12]

A year later, he returned to the United States and became an assistant professor at Harvard Medical School. Springer was promoted to associate professor in 1983 and was appointed Latham Family Professor in 1989. [3]

Outside of Harvard, Springer was the 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] [13]

Since 2012, Springer has been a Senior Investigator at the Research Program in Cellular and Molecular Medicine of the Boston Children's Hospital. [3]

Springer is involved in a number of business ventures. He founded LeukoSite in 1993, [5] which went public in 1997 and was acquired by Millennium Pharmaceuticals the next year. [14] He co-founded biotechnology companies Scholar Rock in 2012 [15] and Morphic Therapeutic in 2015. [16] He was also an early investor in Selecta Biosciences and Editas Medicine. [14]

Springer was a founding investor of the then-startup company 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]

In 2017, Springer co-founded the 501(c)(3) organization Institute for Protein Innovation, which focuses on antibody research, [21] with him providing a $10 million foundational grant. [14]

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. [22] He found a monoclonal antibody that binds a new protein prevents cytotoxic T cells interacting with antigens, and named the protein LFA-1. [23] 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] [24] 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. [25]

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. [26] [27] His innovative use of monoclonal antibodies in these discoveries [28] paved the way for the development of therapeutic antibodies, known as selective adhesion molecule inhibitors, to treat autoimmune diseases.

In addition, Springer identified the steps through which white blood cells move out of the circulatory system towards the site of damage or infection. [29]

More recently, research at Springer's group has expanded to malaria vaccine, transforming growth factor beta (TGF-β) signaling, and how von Willebrand factor starts the process of stopping bleeding. [9]

Personal life

Springer is a gongshi collector. [30]

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. [31] [32]

Springer founded and has made contributions to the Institute for Protein Innovation, a Boston-based nonprofit biomedical research organization. He also has endowed professorships at Harvard Medical School, Boston Children's Hospital, and Berkeley. [33] [34]

Honors and awards

He was a Phi Beta Kappa graduate from the University of California, Berkeley. [10]

Related Research Articles

Leukocyte adhesion deficiency (LAD) is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections. LAD is currently divided into three subtypes: LAD1, LAD2, and the recently described LAD3, also known as LAD-1/variant. In LAD3, the immune defects are supplemented by a Glanzmann thrombasthenia-like bleeding tendency.

<span class="mw-page-title-main">ICAM-1</span> Mammalian protein found in Homo sapiens

ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by rhinovirus as a receptor for entry into respiratory epithelium.

<span class="mw-page-title-main">Immunological synapse</span> Interface between lymphocyte and target cell

In immunology, an immunological synapse is the interface between an antigen-presenting cell or target cell and a lymphocyte such as a T cell, B cell, or natural killer cell. The interface was originally named after the neuronal synapse, with which it shares the main structural pattern. An immunological synapse consists of molecules involved in T cell activation, which compose typical patterns—activation clusters. Immunological synapses are the subject of much ongoing research.

<span class="mw-page-title-main">Integrin alpha X</span> Mammalian protein found in Homo sapiens

CD11c, also known as Integrin, alpha X (ITGAX), is a gene that encodes for CD11c.

<span class="mw-page-title-main">Integrin alpha L</span> Mammalian protein found in Homo sapiens

Integrin, alpha L , also known as ITGAL, is a protein that in humans is encoded by the ITGAL gene. CD11a functions in the immune system. It is involved in cellular adhesion and costimulatory signaling. It is the target of the drug efalizumab.

<span class="mw-page-title-main">CD2</span> Cell adhesion molecule found on the surface of T cells and natural killer

CD2 is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells. It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette receptor.

Lymphocyte function-associated antigen 1 (LFA-1) is an integrin found on lymphocytes and other leukocytes. LFA-1 plays a key role in emigration, which is the process by which leukocytes leave the bloodstream to enter the tissues. LFA-1 also mediates firm arrest of leukocytes. Additionally, LFA-1 is involved in the process of cytotoxic T cell mediated killing as well as antibody mediated killing by granulocytes and monocytes. As of 2007, LFA-1 has 6 known ligands: ICAM-1, ICAM-2, ICAM-3, ICAM-4, ICAM-5, and JAM-A. LFA-1/ICAM-1 interactions have recently been shown to stimulate signaling pathways that influence T cell differentiation. LFA-1 belongs to the integrin superfamily of adhesion molecules.

<span class="mw-page-title-main">Integrin beta 2</span> Mammalian protein found in Homo sapiens

In molecular biology, CD18 is an integrin beta chain protein that is encoded by the ITGB2 gene in humans. Upon binding with one of a number of alpha chains, CD18 is capable of forming multiple heterodimers, which play significant roles in cellular adhesion and cell surface signaling, as well as important roles in immune responses. CD18 also exists in soluble, ligand binding forms. Deficiencies in CD18 expression can lead to adhesion defects in circulating white blood cells in humans, reducing the immune system's ability to fight off foreign invaders.

Lymphocyte homing receptors are cell adhesion molecules expressed on lymphocyte cell membranes that recognize addressins on target tissues. Lymphocyte homing refers to adhesion of the circulating lymphocytes in blood to specialized endothelial cells within lymphoid organs. These diverse tissue-specific adhesion molecules on lymphocytes and on endothelial cells contribute to the development of specialized immune responses.

CD58, or lymphocyte function-associated antigen 3 (LFA-3), is a cell adhesion molecule expressed on Antigen Presenting Cells (APCs), particularly macrophages, and other tissue cells.

<span class="mw-page-title-main">Leukocyte extravasation</span> Passage of a leukocyte

Leukocyte extravasation is the movement of leukocytes out of the circulatory system and towards the site of tissue damage or infection. This process forms part of the innate immune response, involving the recruitment of non-specific leukocytes. Monocytes also use this process in the absence of infection or tissue damage during their development into macrophages.

<span class="mw-page-title-main">ICAM3</span> Mammalian protein found in Homo sapiens

Intercellular adhesion molecule 3 (ICAM3) also known as CD50, is a protein that in humans is encoded by the ICAM3 gene. The protein is constitutively expressed on the surface of leukocytes, which are also called white blood cells and are part of the immune system. ICAM3 mediates adhesion between cells by binding to specific integrin receptors. It plays an important role in the immune cell response through its facilitation of interactions between T cells and dendritic cells, which allows for T cell activation. ICAM3 also mediates the clearance of cells undergoing apoptosis by attracting and binding macrophages, a type of cell that breaks down infected or dying cells through a process known as phagocytosis, to apoptotic cells.

<span class="mw-page-title-main">ICAM2</span> Protein-coding gene in the species Homo sapiens

Intercellular adhesion molecule 2 (ICAM2), also known as CD102, is a human gene, and the protein resulting from it.

<span class="mw-page-title-main">CD93</span>

CD93 is a protein that in humans is encoded by the CD93 gene. CD93 is a C-type lectin transmembrane receptor which plays a role not only in cell–cell adhesion processes but also in host defense.

The following outline is provided as an overview of and topical guide to immunology:

Christopher Edward Rudd, is a Canadian-born immunologist-biochemist. He is currently Professor of Medicine at the Universite de Montreal and Director, Immunology-Oncology at the Centre de Recherche Hôpital Maisonneuve-Rosemont (CR-HMR).

<span class="mw-page-title-main">Alan M. Krensky</span>

Alan Krensky is executive for development at Northwestern Medicine and vice dean for development and alumni relations at Northwestern's Feinberg School of Medicine. He was previously senior investigator in the Laboratory of Cellular and Molecular Biology at the National Institutes of Health (NIH) and served as the first director of the Office of Portfolio Analysis and Strategic Initiatives (OPASI) and a deputy director of NIH. He was Associate Dean for Children’s Health and the Shelagh Galligan Professor of Pediatrics at Stanford University.

Jack Leonard Strominger is the Higgins Professor of Biochemistry at Harvard University, specializing in the structure and function of human histocompatibility proteins and their role in disease. He won the Albert Lasker Award for Basic Medical Research in 1995.

<span class="mw-page-title-main">James P. Allison</span> American immunologist and Nobel laureate (born 1948)

James Patrick Allison is an American immunologist and Nobel laureate who holds the position of professor and chair of immunology and executive director of immunotherapy platform at the MD Anderson Cancer Center at the University of Texas.

<span class="mw-page-title-main">Nancy Hogg</span> Immunologist

Nancy Hogg FMedSci is an immunologist who has made major contributions in the field of adhesion molecules, focusing on the integrins expressed by leukocytes. Hogg was elected to the Academy of Medical Sciences in 2002 and currently holds an emeritus position at the Francis Crick Institute, London.

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. ↑ "Timothy A. Springer". Harvard Medical School. Archived from the original on June 25, 2023. Retrieved June 25, 2023.
  9. 1 2 "Springer Lab - Research". Harvard Medical School. Archived from the original on June 25, 2023. Retrieved June 25, 2023.
  10. 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. 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.
  15. ↑ 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.
  16. ↑ "Timothy Springer, PhD". Morphic Therapeutic. Archived from the original on June 29, 2023. Retrieved June 29, 2023.
  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. ↑ 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.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ 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.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ "Chafen Lu, Ph.D." Harvard Medical School. Archived from the original on June 30, 2023. Retrieved June 30, 2023.
  33. ↑ 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.
  34. ↑ Gigi Zamora (May 24, 2023). "Billionaire Professor Tim Springer Donates $210 Million To Biomedical Research Nonprofit". Forbes.com.
  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 Alan Springer". American Academy of Arts and Sciences. 15 May 2023. Archived from the original on June 28, 2023. Retrieved June 28, 2023.
  38. ↑ "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.
  39. ↑ "Timothy A. Springer". John Simon Guggenheim Memorial Foundation. Archived from the original on July 3, 2023. Retrieved July 3, 2023.
  40. ↑ "Elected Fellows". American Association for the Advancement of Science. Archived from the original on July 3, 2023. Retrieved July 3, 2023.
  41. ↑ 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.
  42. ↑ "AAI-Thermo Fisher Meritorious Career Award Past Recipients". American Association of Immunologists. Archived from the original on July 4, 2023. Retrieved July 4, 2023.
  43. ↑ "Henry M. Stratton Medal Recipients (Formerly Lecture)". American Society of Hematology. Archived from the original on July 4, 2023. Retrieved July 4, 2023.
  44. ↑ "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.
  45. ↑ "Timothy A. Springer". Gairdner Foundation. 20 October 2019. Archived from the original on July 4, 2023. Retrieved July 4, 2023.
  46. ↑ "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.
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