2011 Nobel Prize
in Physiology or Medicine
Director of the Center for the Genetics of Host Defense,
UT Southwestern Medical Center
Member, National Academy of Sciences
Member, Institute of Medicine
Member, American Academy of Arts and Sciences
Member, German Academy of Sciences
Bruce A. Beutler, MD and Jules A. Hoffmann of Strasbourg University in France shared the 2011 Nobel Prize in Physiology or Medicine “for their discoveries concerning the activation of innate immunity,” the first step in the body’s immune response. The late Dr. Ralph M. Steinman of Rockefeller University in New York was also honored in 2011.
Dr. Beutler has studied innate immunity since the early 1980s. During a brief fellowship and faculty appointment at Rockefeller University, he isolated tumor necrosis factor (TNF), and identified it as one of the most important mediators of LPS-induced inflammation. He then returned to UT Southwestern as a faculty member and Howard Hughes Medical Institute Investigator from 1986 to 2000.
His seminal work during this period was broadly relevant to host responses to viral infection, cancer, and autoimmunity, and ultimately led to the Nobel Prize. He developed recombinant inhibitors of TNF that have since been used in the treatment of rheumatoid arthritis and other diseases. And he positionally cloned the receptor for LPS, thereby revealing the Toll like receptors as sensors of conserved molecules of microbial origin.
Between 2000 and 2011, Dr. Beutler worked at The Scripps Research Institute in La Jolla, Calif. He pioneered the use of random germline mutagenesis to dissect TLR signaling pathways, and during that period identified mutations in 20 genes critical for this process. Since 2011, he has resumed his work at UT Southwestern Medical center, where he established one of the largest mouse mutagenesis programs in the world: the only such program capable of identifying causative mutations in real time. He and his group have identified several hundred mutations that cause abnormalities in mice. Many of these mutations have important implications in infectious diseases or autoimmune conditions. Dr. Beutler’s team also has catalogued over a quarter of a million other mutations that change coding sense in the mouse, stored in an archive that eventually will encompass all mouse genes.
Dr. Beutler, a Regental Professor at UT Southwestern who holds the Raymond and Ellen Willie Distinguished Chair in Cancer Research, in Honor of Laverne and Raymond Willie Sr., earned his medical degree from the University of Chicago after graduating from the University of California, San Diego. His postgraduate career at UT Southwestern included an internal medicine internship and neurology residency.
Honors & Awards
- 2015 Lindahl Lecturer, Napa Pain Conference
- 2013 Korsmeyer Award
- 2011 Nobel Prize in Physiology or Medicine
- 2011 Shaw Prize in Life Science and Medicine
- 2009 Will Rogers Institute Annual Prize for Scientific Research
- 2009 Albany Medical Center Prize in Medicine and Biomedical Research
- 2007 Balzan Prize
- 2006 Gran Prix Charles-Léopold Mayer from the Académie des Sciences in France
- 2004 Robert Koch Prize
- Poltorak, A., He, X., Smirnova, I., Liu, M. Y., Van Huffel, C., Du, X., … & Freudenberg, M. (1998). Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science, 282(5396), 2085-2088.
- Beutler, B., Milsark, I. W., & Cerami, A. C. (1985). Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science, 229(4716), 869-871.
- Tracey, K. J., Beutler, B., Lowry, S. F., Merryweather, J., Wolpe, S., Milsark, I. W., … & Albert, J. D. (1986). Shock and tissue injury induced by recombinant human cachectin. Science, 234(4775), 470-474.
- Beutler, B., & Cerami, A. (1987). Cachectin: more than a tumor necrosis factor. New England Journal of Medicine, 316(7), 379-385.
- Beutler, B., & Cerami, A. (1986). Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature, 320(6063), 584.
- Beutler, B., & Cerami, A. (1989). The biology of cachectin/TNF–a primary mediator of the host response. Annual review of immunology, 7(1), 625-655.
- Bazzoni, F., & Beutler, B. (1996). The tumor necrosis factor ligand and receptor families. New England Journal of Medicine, 334(26), 1717-1725.
- Beutler, B., Krochin, N., Milsark, I. W., Luedke, C., & Cerami, A. (1986). Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science, 232(4753), 977-980.
- Dinarello, C. A., Cannon, J. G., Wolff, S. M., Bernheim, H. A., Beutler, B., Cerami, A., … & O’Connor, J. V. (1986). Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. Journal of Experimental Medicine, 163(6), 1433-1450.
- Beutler, B. (2004). Inferences, questions and possibilities in Toll-like receptor signalling. Nature, 430(6996), 257.
- Hoebe, K., Janssen, E., & Beutler, B. (2004). The interface between innate and adaptive immunity. Nature immunology, 5(10), 971.
- Beutler, B., & Rietschel, E. T. (2003). Innate immune sensing and its roots: the story of endotoxin. Nature Reviews Immunology, 3(2), 169.
- Beutler, B. (2004). Innate immunity: an overview. Molecular immunology, 40(12), 845-859.
- Hoebe, K., Georgel, P., Rutschmann, S., Du, X., Mudd, S., Crozat, K., … & Beutler, B. (2005). CD36 is a sensor of diacylglycerides. Nature, 433(7025), 523.
- Theofilopoulos, A. N., Baccala, R., Beutler, B., & Kono, D. H. (2005). Type I interferons (α/β) in immunity and autoimmunity. Annu. Rev. Immunol., 23, 307-335.