Bruce A. Beutler

Bruce A. Beutler, born in Chicago on 29 December 1957, is a US citizen. He is a Professor of Immunology at The Scripps Research Institute, La Jolla, and a Professor and Chairman of the Department of Genetics at the same institution. He is known for his molecular and genetic studies of inflammation and innate immunity, and in particular, for his isolation of tumor necrosis factor, demonstration of its important role in septic shock, and for positional cloning of the mammalian lipopolysaccharide (LPS) response gene, which identified the LPS receptor, and showed that the mammalian Toll-like receptors act as sensors of infection. He has been a leading advocate of forward genetic analysis of immunity, in which mutations that alter immune function are created through a random process, detected by their phenotypic effects, and then isolated by positional cloning.

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Beutler received his B.A. from the University of California, San Diego in 1976 and his M.D. from the University of Chicago in 1981. From 1981 to 1983 he continued his medical training at the University of Texas Southwestern Medical Center at Dallas.

Between 1983 and 1985 he was Fellow at Rockefeller University of New York, where he became an Assistant Professor in 1985. He was also an Associate Physician at the Rockefeller University Hospital between 1984 and 1986.

He returned to Dallas in 1986 as an Assistant Professor in the Department of Internal Medicine of the University of Texas Southwestern Medical Center at Dallas, where he became an Associate Professor in 1990 and a Professor in 1996. In Dallas he was also an Assistant Investigator at the Howard Hughes Medical Institute from 1986, and became an Associate Investigator in 1991. Since 2000 he has been at The Scripps Research Institute.

Beutler received the famous Balzan Prize in 2007 together with Jules A. Hoffmann for his studies of innate immunity. Other notable honors have included the William B. Coley Award (in 2006, shared with Shizuo Akira), the Gran Prix Charles-Leopold-Mayer of the Académie des Sciences, France (in 2006), and the Robert Koch Prize (in 2004, shared with Jules A. Hoffmann and Shizuo Akira). He is an elected Member of the American Society for Clinical Investigation (1990) and the Association of American Physicians (2001).

Publications

1. B. Beutler, J. Mahoney, N. Le Trang, P. Pekala and A. Cerami. Purification of cachectin, a lipoprotein lipase suppressing hormone secreted by endotoxin induced RAW 264.7 cells. J.Exp.Med. 161:984 995, (1985).

2. B. Beutler, D. Greenwald, J.D. Hulmes, M. Chang, Y. C.E. Pan, J. Mathison, R. Ulevitch and A. Cerami. Identity of tumour necrosis factor and the macrophage secreted factor cachectin. Nature 316:552 554, (1985).

3. B. Beutler, I.W. Milsark and A. Cerami. Passive immunization against cachectin/tumor necrosis factor (TNF) protects mice from the lethal effect of endotoxin. Science 229:869 871, (1985).

4. D. Caput, B. Beutler, K. Hartog, S. Brown Shimer and A. Cerami. Identification of a common nucleotide sequence in the 3' untranslated region of mRNA molecules specifying inflammatory mediators. Proc.Natl.Acad.Sci.U.S.A. 83:1670 1674, (1986).

5. K. Peppel, D. Crawford, and B. Beutler. A tumor necrosis factor (TNF) receptor IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity. J.Exp.Med. 174:1483 1489, (1991).

6. A. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, C. Galanos, M. Freudenberg, P. Ricciardi-Castagnoli, B. Layton, and B. Beutler. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in the TLR4 gene. Science 282: 2085-2088, (1998)

7. I. Smirnova, N. Mann, A. Dols, H.H. Derkx, M. Hibberd, M. Levin, and B. Beutler. Assay of locus-specific genetic load implicates rare TLR4 mutations in meningococcal susceptibility. Proc.Natl.Acad.Sci. U.S.A. 100:6075-6080, (2003).

8. K. Hoebe, X. Du, P. Georgel, E. M. Janssen, K. Tabeta, S.O. Kim, J. Goode, P. Lin, N. Mann, S. Mudd, K. Crozat, S. Sovath, J. Han and B. Beutler. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424:743-748, (2003).

9. K. Hoebe, E.M. Janssen, S.O. Kim, L. Alexopoulou, R.A. Flavell, J. Han and B. Beutler. Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways. Nature Immunol. 4:1223-1229, (2003).

10. K. Hoebe, P. Georgel, S. Rutschmann, X. Du, S. Mudd, K. Crozat, S. Sovath, L. Shamel, T. Hartung,U. Zähringer, and B. Beutler. CD36 is a sensor of diacylglycerides. Nature 433:523-527, (2005).

11. Z. Jiang, P. Georgel, X. Du, L. Shamel, S. Sovath, S. Mudd, and B. Beutler. CD14 is required for MyD88-independent LPS signaling. Nature Immunology 6:565-570, (2005).

12. K. Tabeta, K. Hoebe, E. M Janssen, X. Du, P. Georgel, K. Crozat, S. Mudd, N. Mann, S. Sovath, J. Goode, L. Shamel, A. Herskovits, D. Portnoy, M. Cooke, L. M. Tarantino, T. Wiltshire, B. E. Steinberg, S. Grinstein, and B. Beutler. The Unc93b1 mutation 3d disrupts exogenous antigen presentation signaling via Toll-like receptors 3, 7 and 9. Nature Immunology 7:156-164, (2006).

13. K. Crozat, K. Hoebe, S. Ugolini, N. A. Hong, E. Janssen, S. Rutschmann, S. Mudd, S. Sovath, E. Vivier, and B. Beutler. Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. J.Exp.Med. 204: 853-863, (2007).

14. B. Croker, K. Crozat, M. Berger, Y. Xia, S. Sovath, I. Eleftherianos, J-L. Imler, and B. Beutler. ATP-sensitive potassium channels mediate survival during infection in mammals and insects. Nature Genetics 39:1453-1460, (2007).

References

• 1 - http://www.scripps.edu/genetics/beutler/