fbpx
Wikipedia

Bruce Beutler

October 21, 2023

Bruce Alan Beutler (/ˈbɔɪtlər/ BOYT-lər; born December 29, 1957) is an American immunologist and geneticist. Together with Jules A. Hoffmann, he received one-half of the 2011 Nobel Prize in Physiology or Medicine, for "discoveries concerning the activation of innate immunity."[1] Beutler discovered the long-elusive receptor for lipopolysaccharide (LPS; also known as endotoxin). He did so by identifying spontaneous mutations in the gene coding for mouse Toll-like receptor 4 (Tlr4) in two unrelated strains of LPS-refractory mice and proving they were responsible for that phenotype.[2] Subsequently, and chiefly through the work of Shizuo Akira, other TLRs were shown to detect signature molecules of most infectious microbes, in each case triggering an innate immune response.[3][4][5][6][7]

Bruce Beutler
University of Texas Southwestern Medical Center, 2021
Photograph by Brian Coats
Born (1957-12-29) December 29, 1957 (age 65)
Chicago, Illinois
NationalityAmerican
Alma materUniversity of Chicago, University of California, San Diego
Spouse(s)Barbara Lanzl (c. 1980-1988; divorced; 3 children)
Awards2011 Nobel Prize in Physiology or Medicine
Scientific career
FieldsImmunology
InstitutionsUniversity of Texas Southwestern Medical Center

The other half of the Nobel Prize went to Ralph M. Steinman for "his discovery of the dendritic cell and its role in adaptive immunity."[1]

Beutler is currently a Regental Professor and Director of the Center for the Genetics of Host Defense at the University of Texas Southwestern Medical Center in Dallas, Texas.[8][9]

Early life and education Edit

Born in Chicago, Illinois, to a Jewish[10] family, Beutler lived in Southern California between the ages of 2 and 18 (1959 to 1977). For most of this time, he lived in city of Arcadia, a northeastern suburb of Los Angeles in the San Gabriel Valley. During these years, he spent much time hiking in the San Gabriel Mountains, and in regional national parks (Sequoia, Yosemite, Joshua Tree, and Grand Canyon), and was particularly fascinated by living things.[11] These experiences impelled an intense interest in biological science. His introduction to experimental biology, acquired between the ages of 14 and 18, included work in the laboratory of his father, Ernest Beutler, then at the City of Hope Medical Center in Duarte, CA. There he learned to assay enzymes of red blood cells and became familiar with methods for protein isolation. He published his studies of an electrophoretic variant of glutathione peroxidase,[12] as well as the inherent catalytic activity of inorganic selenite,[13] at the age of 17.

Beutler also worked in the City of Hope laboratory of Susumu Ohno, a geneticist known for his studies of evolution, genome structure, and sex differentiation in mammals. Ohno hypothesized that the major histocompatibility complex proteins served as anchorage sites for organogenesis-directing proteins.[14] He further suggested that H-Y antigen, a minor histocompatibility protein encoded by a gene on the Y chromosome and absent in female mammals, was responsible for directing organogenesis of the indifferent gonad to form a testis. In studying H-Y antigen,[15] Beutler became conversant with immunology and mouse genetics during the 1970s. While a college student at the University of California at San Diego, Beutler worked in the laboratory of Dan Lindsley, a Drosophila geneticist interested in spermatogenesis and spermiogenesis in the fruit fly. There, he learned to map phenotypes to chromosomal regions using visible phenotypic markers.[11] He also worked in the laboratory of Abraham Braude, an expert in the biology of LPS.

Beutler received his secondary school education at Polytechnic School in Pasadena, California. A precocious student, he graduated from high school at the age of 16, enrolled in college at the University of California, San Diego, and graduated with a BA degree at the age of 18 in 1976. He then enrolled in medical school at the University of Chicago in 1977 and received his M.D. degree in 1981 at the age of 23.[16] From 1981 to 1983 Beutler continued his medical training at the University of Texas Southwestern Medical Center in Dallas, Texas, as an intern in the Department of Internal Medicine, and as a resident in the Department of Neurology. However, he found clinical medicine less interesting than laboratory science, and decided to return to the laboratory.

Scientific contributions Edit

Isolation of tumor necrosis factor and discovery of its inflammation-promoting effect Edit

Beutler’s focus on innate immunity began when he was a postdoctoral associate and later an assistant professor in the lab of Anthony Cerami at Rockefeller University (1983-1986). Drawing upon skills he had acquired earlier, he isolated mouse “cachectin” from the conditioned medium of LPS-activated mouse macrophages.[17] Cachectin was hypothesized by Cerami to be a mediator of wasting in chronic disease. Its biological activity, the suppression of lipoprotein lipase synthesis in adipocytes, was thought to contribute to wasting, since lipoprotein lipase cleaves fatty acids from circulating triglycerides, allowing their uptake and re-esterification within fat cells.[18] By sequential fractionation of LPS-activated macrophage medium, measuring cachectin activity at each step, Beutler purified cachectin to homogeneity.[19] Determining its N-terminal sequence, he recognized it as mouse tumor necrosis factor (TNF), and showed that it had strong TNF activity; moreover that human TNF, isolated by a very different assay, had strong cachectin activity.[18]

Human TNF, isolated contemporaneously by other workers,[20] had to that time been defined only by its ability to kill cancer cells. The discovery of a separate role for TNF as a catabolic switch was of considerable interest. Of still greater importance, Beutler demonstrated that TNF acted as a key mediator of  endotoxin-induced shock.[21] This he accomplished by raising an antibody against mouse TNF, which he used to neutralize TNF in living mice challenged with lipopolysaccharide (LPS).[21] The often-lethal systemic inflammatory response to LPS was significantly mitigated by passive immunization against TNF. The discovery that TNF caused an acute systemic inflammatory disease (LPS-induced shock) presaged its causative role in numerous chronic inflammatory diseases. With J.-M. Dayer, Beutler demonstrated that purified TNF could cause inflammation-associated responses in cultured human synoviocytes: secretion of collagenase and prostaglandin E2.[22]  This was an early hint that TNF might be causally important in rheumatoid arthritis (as later shown by Feldmann, Brennan, and Maini[23]). Beutler also demonstrated the existence of TNF receptors on most cell types,[19] and correctly inferred the presence of two types of TNF receptor distinguished by their affinities, later cloned and designated p55 and p75 TNF receptors to denote their approximate molecular weights.[24][25][26][27][28] Before a sensitive immunoassay for TNF was feasible, Beutler used these receptors in a binding competition assay using radio-iodinated TNF as a tracer, which allowed him to precisely measure TNF in biological fluids.[29]

Invention of TNF inhibitors Edit

Beutler was recruited to a faculty position at UT Southwestern Medical Center and the Howard Hughes Medical Institute in 1986. Aware that TNF blockade might have clinical applications, he (along with a graduate student, David Crawford, and a postdoctoral associate, Karsten Peppel) invented and patented recombinant molecules expressly designed to neutralize TNF in vivo (Patent No. US5447851B1).[30] Fusing the binding portion of TNF receptor proteins to the heavy chain of an immunoglobulin molecule to force receptor dimerization,[30] they produced chimeric reagents with surprisingly high affinity and specificity for both TNF and a closely related cytokine called lymphotoxin, low antigenicity, and excellent stability in vivo. The human p75 receptor chimeric protein was later used extensively as the drug Etanercept in the treatment of rheumatoid arthritis, Crohn's disease, psoriasis, and other forms of inflammation. Marketed by Amgen, Etanercept achieved more than $74B in sales.[31]

Discovery of the LPS receptor, and the role of TLRs in innate immune sensing Edit

From the mid-1980s onward Beutler was interested in the mechanism by which LPS activates mammalian immune cells (chiefly macrophages,[18][21] but dendritic cells and B cells as well), sometimes leading to uncontrollable Gram negative septic shock,[32][33][34] but also promoting the well-known adjuvant effect of LPS,[35] and B cell mitogenesis[36][37] and antibody production. A single, highly specific LPS receptor was presumed to exist as early as the 1960s, based on the fact that allelic mutations in two separate strains of mice, affecting a discrete genetic locus on chromosome 4 termed Lps, abolished LPS sensing.[36][38] Although this receptor had been widely pursued, it remained elusive. Beutler reasoned that in finding the LPS receptor, insight might be gained into the first molecular events that transpire upon an encounter between the host and microbial invaders.[39]

Utilizing positional cloning in an effort that began in 1993 and lasted five years, Beutler, together with several postdoctoral associates including Alexander Poltorak, measured TNF production as a qualitative phenotypic endpoint of the LPS response. Analyzing more than 2,000 meioses, they confined the LPS receptor-encoding gene to a region of the genome encompassing approximately 5.8 million base pairs of DNA.[2] Sequencing most of the interval, they identified a gene within which each of two LPS-refractory strains of mice (C3H/HeJ and C57BL/10ScCr) had deleterious mutations. The gene, Tlr4, encoded a cell surface protein with cytoplasmic domain homology to the interleukin-1 receptor, and several other homologous genes that were scattered across the mouse genome. Beutler and his team thus proved that one of the mammalian Toll-like receptors, TLR4, acts as the membrane-spanning component of the mammalian LPS receptor complex.[2][40][41] They also showed that while mouse TLR4 is activated by a tetra-acylated LPS-like molecule (lipid IVa), human TLR4 is not, recapitulating the species specificity for LPS partial structures.[41] It was deduced that direct contact between TLR4 and LPS is a prerequisite for cell activation.[41]  Later, an extracellular component of the LPS receptor complex, MD-2 (also known as lymphocyte antigen 96), was identified by R. Shimazu and colleagues.[42] The structure of the complex, with and without LPS bound, was solved by Jie-Oh Lee and colleagues in 2009.[43]

Jules Hoffmann and colleagues had earlier shown that the Drosophila Toll protein, originally known for its role in embryogenesis, was essential for the antimicrobial peptide response to fungal infection.[44]  However, no molecule derived from fungi actually became bound to Toll; rather, a proteolytic cascade led to the activation of an endogenous ligand, the protein Spätzle. This activated NF-kB within cells of the fat body, leading to antimicrobial peptide secretion.

Aware of this work, Charles Janeway and Ruslan Medzhitov overexpressed a modified version of human TLR4 (which they called ‘h-Toll’) and found it capable of activating the transcription factor NF-κB in mammalian cells.[45] They speculated that TLR4 was a “pattern recognition receptor.”  However, they provided no evidence that TLR4 recognized any molecule of microbial origin. If a ligand did exist, it might have been endogenous (as in the fruit fly, where Toll recognizes the endogenous protein Spätzle, or as in the case of the IL-1 receptor, which recognizes the endogenous cytokine IL-1). Indeed, numerous cell surface receptors, including the TGFβ receptor, B cell receptor, and T cell receptor activate NF-κB. In short, it was not clear what TLR4 recognized, nor what its function was. Separate publications, also based on transfection/overexpression studies, held that TLR2 rather than TLR4 was the LPS receptor.[46][47]

The genetic evidence of Beutler and coworkers correctly identified TLR4 as the specific and non-redundant cell surface receptor for LPS, fully required for virtually all LPS activities. This suggested that other TLRs (of which ten are now known to exist in humans) might also act as sensors of infection in mammals,[48] each detecting other signature molecules made by microbes whether or not they were pathogens in the classical sense of the term. The other TLRs, like TLR4, do indeed initiate innate immune responses. By promoting inflammatory signaling, TLRs can also mediate pathologic effects including fever, systemic inflammation, and shock. Sterile inflammatory and autoimmune diseases such as systemic lupus erythematosus also elicit TLR signaling, and disruption of signaling from the nucleic acid sensing TLRs can favorably modify the disease phenotype.[49][50][51][52][53][54][55][56]

Random Germline Mutagenesis/Forward Genetics in the mouse Edit

After completing the positional cloning of the Lps locus in 1998, Beutler continued to apply a forward genetic approach to the analysis of immunity in mammals. In this process, germline mutations that alter immune function are created in mice through a random process using the alkylating agent ENU, detected by their phenotypic effects, and then isolated by positional cloning.[57] This work disclosed numerous essential signaling molecules required for the innate immune response,[58][59][60][61][62][63][64] and helped to delineate the biochemistry of innate immunity. Among the genes detected was Ticam1, implicated by an ENU-induced phenotype called Lps2.[58] The encoded protein TICAM1, also known as TRIF, was a new adaptor molecule, binding to the cytoplasmic domains of both TLR3 and TLR4, and needed for signaling by each.

Another phenotype, called 3d to connote a “triple defect” in TLR signaling, affected a gene of unknown function called Unc93b1.[60] TLRs 3, 7, and 9 (nucleic acid sensing TLRs) failed to signal in homozygotes for the mutation. These TLRs were found to be endosomal, and physically interact with the UNC93B1 protein which transports them to the endosomal compartment.[65]  Humans with mutations in UNC93B1, the human ortholog of the same gene, were subsequently found to be susceptible to recurrent Herpes simplex virus (HSV) encephalitis, in which reactivation of latent virus occurs repeatedly in the trigeminal ganglion at the base of the midbrain, leading to cortical neuron death.[66]

Yet another protein needed to make the endosomal environment suitable for TLR signaling was SLC15A4, identified based on the phenotype feeble.[67] feeble was identified in a screen in which immunostimulatory DNA was administered to mice intravenously with measurement of the systemic type I interferon response. Failure of this response, which is dependent on TLR9 signaling from plasmacytoid dendritic cells (pDC) was observed in homozygous mutants, and subsequently, failure of TLR7 (but not TLR3) signaling was observed as well. Because the feeble mutation suppressed SLE in mice,[52] the SLC15A4 protein has become a target of interest for drug development.[68]

In all, Beutler and colleagues detected 77 mutations in 36 genes in which ENU-induced mutations created defects of TLR signaling, detected due to faulty TNF and/or interferon responses. These genes encoded all TLRs kept under surveillance in screening, all of the four adapter proteins that signal from TLRs, kinases and other signaling proteins downstream, chaperones needed to escort TLRs to their destinations, proteins that promote the availability of TLR ligands, proteins involved in vesicle transport, and proteins involved in transcriptional responses to TLR signaling, or the post-translational processing of TNF and/or type I interferons (the proteins assayed in screening).

Beutler and colleagues also used ENU mutagenesis to study the global response to a defined infectious agent. They measured susceptibility to mouse cytomegalovirus (MCMV) and identified numerous genes that make a life-or-death difference during infection, terming this set of genes the MCMV "resistome".[69][70] These genes were grouped into "sensing," "signaling," "effector," "homeostatic," and "developmental" categories, some of which were wholly unexpected. In the homeostatic category, for example, Kir6.1 ATP-sensitive potassium channels in the smooth muscle of the coronary arteries serve an essential role in the maintenance of blood flow during MCMV infection, and mutations that damage these channels cause sudden death during infection.[71]

Other genetic screens in the Beutler laboratory were used to identify genes that mediate homeostatic adaptations of the intestinal epithelium following a cytotoxic insult;[72][73][74][75][76][77][78] prevent allergic responses,[79] diabetes,[80][81] or obesity;[82][83][84] support normal hematopoiesis;[85][86][87][88][89][90][91][92][93][94] and enable humoral and cellular immunity.[95][96][97][98] Some of these (beginning ~2015) were identified by a new process called automated meiotic mapping, which enabled greatly accelerated mutation identification compared to traditional genetic mapping (see below). In the course of their work, Beutler and his colleagues also discovered genes required for biological processes such as normal iron absorption,[99] hearing,[100] pigmentation,[101][102] metabolism,[82][84][103][104][105] and embryonic development.[106] Many human diseases were ultimately linked to variants in the corresponding human genes after initial identification in the mouse by the Beutler laboratory,[66][107][108][109] or by the laboratories of collaborating investigators.[110][111][112]

Invention of Automated Meiotic Mapping Edit

Prior to 2013, despite the development of methods for massively parallel sequencing and their application in finding induced germline mutations,[113][114][115] positional cloning remained a slow process, limited by the need to genetically map mutations to chromosomal intervals to ascertain which induced mutation (among the average of approximately 60 changes in coding and splicing function induced per pedigree) was responsible for an observed phenotype. This required expansion of a mutant stock, outcrossing to a mapping strain, backcrossing, and genotypic and phenotypic analysis of F2 offspring. Moreover, when phenotypic screening was performed prior to positional cloning, only large effect size mutations (producing essentially qualitative phenotypes) were recoverable.

Beutler invented a means of instantly identifying ENU-induced mutations that cause phenotypes.[116] The process, called automated meiotic mapping (AMM), eliminates the need to breed mutant mice to a mapping strain as required in classical genetic mapping and flags causative mutations as soon as phenotypic assay data are collected. In a laboratory setting, it accelerates positional cloning approximately 200-fold, and permits ongoing measurement of genome saturation as mutagenesis progresses.[117] Not only qualitative phenotypes, but subtle quantitative phenotypes, are detectable and mapped to individual mutations; hence the sensitivity of forward genetics is dramatically increased. AMM depends on statistical computation to detect associations between mutations in either the homozygous or heterozygous state and deviant phenotypes.[116] In addition, machine learning software, trained on the outcome of many thousands of experiments in which putative causative mutations were re-created and re-assayed for phenotype, is used to assess data quality.[118] As of 2022, more than 260,000 ENU-induced non-synonymous coding or splice site mutations had been assayed for phenotypic effects, and more than 5,800 mutations in approximately 2,500 genes had been declared causative of phenotype(s). For certain screens, such as flow cytometry performed on the blood of germline mutant mice, more than 55% saturation of the genome has been achieved (i.e., more than 55% of all genes in which mutations will create flow cytometric aberrations in the peripheral blood have been detected, most of them based on assessment of multiple alleles, as of July 2021).[118]

AMM led to the discovery of many new immunodeficiency disorders,[88][89][90][91][92][93][94][85][98] and disorders of bone morphology or mineral density,[111][112] vision,[119] and metabolism.[82][84][104][105] Of note, AMM was used in the identification of a chemosensor that mediates innate fear behavior in mice and an autism gene found first in mice and then shown to cause autism in humans.[110][120] AMM has also permitted high speed searches for mutations that suppress or augment disease phenotypes; for example, the development of autoimmune (Type 1) diabetes in mice of the NOD strain.[80][81] It offers a rational way to investigate the pathogenesis of complex disease phenotypes in general, in which many loci invariably contribute to susceptibility or resistance to disease, and disease occurs in those individuals with an unfavorable imbalance between these opposing influences.

Developing drugs that activate TLRs Edit

Beutler has collaborated with Dale L. Boger and his research group to identify synthetic small molecule agonists of mammalian TLRs, which may be used in combination with defined molecular antigens to precisely target and coordinate innate and adaptive immune responses. Neoseptins, small molecules with no relationship to the structure of LPS, were shown to bind to the TLR4-MD2 complex in such a manner that two drug molecules trigger a conformational change similar to that elicited by an authentic LPS molecule. Diprovocims, which bear no structural similarity to bacterial lipopeptides, activate the TLR1-TLR2 heterodimer complex that normally acts as a receptor for tri-acylated lipopeptide molecules. These studies demonstrated that TLR2 and TLR4 can indeed respond to molecules other than classical microbial ligands, and set a new standard for verifying such interactions, in that X-ray crystallography was used to demonstrate the binding of neoseptins and diprovocims to their respective TLR targets at atomic level resolution. Beutler and colleagues also showed, again using X-ray crystallography combined with biological assays, that endogenous sulfatides are capable of binding to the TLR4-MD2 complex, causing its activation.[121][122][123][124][125][126][127]

Awards and recognition Edit

 
Jules A. Hoffmann, Göran K. Hansson (chairman of the Nobel Committee for Physiology or Medicine) and Beutler
 
Jules A. Hoffmann (background) and Beutler
 
Bruce Beutler at the Nobel Prize press conference at Karolinska, Solna

Awards Edit

  • 1993 - Alexander von Humboldt Fellow; Germany
  • 1994 - Young Investigator Award (American Federation for Clinical Research); United States
  • 2001 - “Highly Cited” Researcher, Institute for Scientific Information; United States
  • 2004 - Robert Koch Prize (Robert Koch Stiftung); Germany (shared with Jules A. Hoffmann and Shizuo Akira)
  • 2006 - William B. Coley Award (Cancer Research Institute); United States (shared with Shizuo Akira)
  • 2006 - Gran Prix Charles-Léopold Mayer (Académie des Sciences); France
  • 2007 - Recipient of NIH/NIGMS MERIT Award; United States
  • 2007 - Balzan Prize (International Balzan Foundation); Italy and Switzerland (shared with Jules A. Hoffmann)
  • 2008 - Frederik B. Bang Award (The Stanley Watson Foundation); United States
  • 2008 - “Citation Laureate,” Thomson Reuters
  • 2009 - Will Rogers Institute Annual Prize for Scientific Research; United States
  • 2009 - Albany Medical Center Prize in Medicine and Biomedical Research; United States (shared with Charles A. Dinarello and Ralph M. Steinman)[128]
  • 2010 - University of Chicago, Professional Achievement Citation; United States
  • 2011 - Shaw Prize; China (shared with Jules A. Hoffmann and Ruslan M. Medzhitov)
  • 2011 - Nobel Prize in Physiology or Medicine; Sweden (shared with Jules A. Hoffmann and Ralph M. Steinman)[1]
  • 2012 - Drexel Medicine Prize in Immunology; United States
  • 2013 - Rabbi Shai Shacknai Memorial Prize in Immunology and Cancer Research, The Hebrew University of Jerusalem; Israel
  • 2013 - Distinguished Service Award, University of Chicago; United States
  • 2013 - Korsmeyer Award; United States
  • 2016 - UCSD Distinguished Alumnus Award; United States

Honorary Doctoral Degrees Edit

  • 2007 - Doctor Med. Honoris Causa, Technical University of Munich; Germany
  • 2009 - Honorary Doctoral Degree, Xiamen University; China
  • 2012 - Honorary Professor, Trinity College; Ireland
  • 2013 - Honorary Professor, Peking University; China
  • 2014 - Honorary Professor, Shanghai Jiao Tong University; China
  • 2014 - Chair of the Beutler Institute Council, Xiamen University; China
  • 2014 - Honorary Professor, Xiamen University; China
  • 2015 - Doctor Honoris Causa, University of Chile; Chile
  • 2015 - Doctor Honoris Causa, University of Marseille; France
  • 2015 - Doctor Honoris Causa, University of Brasilia; Brazil
  • 2015 - Doctor Honoris Causa,[129] Norwegian University of Science and Technology (NTNU); Norway
  • 2015 - Honorary Professor at Naresuan University; Thailand
  • 2016 - Honorary Doctorate, University of Athens; Greece
  • 2017 - Doctor Med. Honoris Causa, University of Ottawa; Canada
  • 2017 - Honorary Professor, Tianjin University; China
  • 2019 - Honorary Degree, Jewish Theological Seminary; United States
  • 2019 - Laurea Magistrale honoris causa in Medicina e Chirurgia (LM41),[130] Universita Magna Grecia of Catanzaro; Italy

Family Edit

Bruce Beutler was the third son of Ernest Beutler (1928-2008) and Brondelle May Beutler (née Fleisher; 1928-2019). His siblings included two older brothers (Steven [b. 1952] and Earl [b. 1954]), and a younger sister, Deborah [b. 1962]).[citation needed]

Ernest Beutler was a hematologist and medical geneticist famed for his studies of G-6-PD deficiency,[131] other hemolytic anemias,[132][133] iron metabolism,[134] glycolipid storage diseases,[135] and leukemias,[136][137] as well as his discovery of X chromosome inactivation.[138] He was a Professor and department chairman at The Scripps Research Institute contemporaneously with Bruce. The two collaborated productively on several topics prior to Ernest Beutler’s death in 2008.[12][13][139][140][141][142]

Both of Ernest Beutler’s parents were physicians.[143] Bruce Beutler’s paternal grandmother, Kathe Beutler (née Italiener, daughter of Anna Rothstein, 1896-1999),[144] was a pediatrician, trained at the Charité hospital in Berlin, earning her medical diploma in 1923. Käthe Italiener married Alfred Beutler in 1925. Also a physician, Alfred Beutler was a cousin to the spectral physicist, Hans G. Beutler (1896-1942), who worked at the Kaiser Wilhelm Institute and the University of Berlin before emigrating to the USA in 1936. He continued his work at the University of Chicago until his death.[145]

Bruce Beutler married Barbara Beutler (née Lanzl) in 1980 and divorced in 1988. Three sons were born to the couple.[citation needed]

See also Edit

References Edit

  1. ^ a b c "Nobel Prize in Physiology or Medicine 2011" (Press release). Nobel Foundation. October 3, 2011.
  2. ^ a b c Poltorak, A.; He, X.; Smirnova, I.; Liu, M. Y.; Van Huffel, C.; Du, X.; Birdwell, D.; Alejos, E.; Silva, M.; Galanos, C.; Freudenberg, M.; Ricciardi-Castagnoli, P.; Layton, B.; Beutler, B. (December 11, 1998). "Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene". Science. 282 (5396): 2085–2088. doi:10.1126/science.282.5396.2085. ISSN 0036-8075. PMID 9851930.
  3. ^ Hemmi, Hiroaki; Kaisho, Tsuneyasu; Takeuchi, Osamu; Sato, Shintaro; Sanjo, Hideki; Hoshino, Katsuaki; Horiuchi, Takao; Tomizawa, Hideyuki; Takeda, Kiyoshi; Akira, Shizuo (January 22, 2002). "Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway". Nature Immunology. 3 (2): 196–200. doi:10.1038/ni758. ISSN 1529-2908. PMID 11812998. S2CID 1694900.
  4. ^ Hemmi, H.; Takeuchi, O.; Kawai, T.; Kaisho, T.; Sato, S.; Sanjo, H.; Matsumoto, M.; Hoshino, K.; Wagner, H.; Takeda, K.; Akira, S. (December 7, 2000). "A Toll-like receptor recognizes bacterial DNA". Nature. 408 (6813): 740–745. Bibcode:2000Natur.408..740H. doi:10.1038/35047123. ISSN 0028-0836. PMID 11130078. S2CID 4405163.
  5. ^ Takeuchi, O.; Hoshino, K.; Kawai, T.; Sanjo, H.; Takada, H.; Ogawa, T.; Takeda, K.; Akira, S. (October 1, 1999). "Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components". Immunity. 11 (4): 443–451. doi:10.1016/s1074-7613(00)80119-3. ISSN 1074-7613. PMID 10549626.
  6. ^ Takeuchi, O.; Kawai, T.; Mühlradt, P. F.; Morr, M.; Radolf, J. D.; Zychlinsky, A.; Takeda, K.; Akira, S. (July 1, 2001). "Discrimination of bacterial lipoproteins by Toll-like receptor 6". International Immunology. 13 (7): 933–940. doi:10.1093/intimm/13.7.933. ISSN 0953-8178. PMID 11431423.
  7. ^ Takeuchi, Osamu; Sato, Shintaro; Horiuchi, Takao; Hoshino, Katsuaki; Takeda, Kiyoshi; Dong, Zhongyun; Modlin, Robert L.; Akira, Shizuo (July 1, 2002). "Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins". Journal of Immunology. 169 (1): 10–14. doi:10.4049/jimmunol.169.1.10. ISSN 0022-1767. PMID 12077222. S2CID 22686400.
  8. ^ Ravindran, S. (2013). "Profile of Bruce A. Beutler". Proceedings of the National Academy of Sciences. 110 (32): 12857–8. Bibcode:2013PNAS..11012857R. doi:10.1073/pnas.1311624110. PMC 3740904. PMID 23858464.
  9. ^ "Center for the Genetics of Host Defense - UT Southwestern, Dallas, TX". Retrieved March 9, 2023.
  10. ^ "Jewish Nobel Prize laureates - Physiology and medicine". www.science.co.il. Retrieved March 29, 2023.
  11. ^ a b "Bruce A. Beutler - Biographical - NobelPrize.org". Retrieved March 9, 2023.
  12. ^ a b Beutler, E.; West, C.; Beutler, B. (October 1974). "Electrophoretic polymorphism of glutathione peroxidase". Annals of Human Genetics. 38 (2): 163–169. doi:10.1111/j.1469-1809.1974.tb01947.x. ISSN 0003-4800. PMID 4467780. S2CID 32294741.
  13. ^ a b Beutler, E.; Beutler, B.; Matsumoto, J. (July 15, 1975). "Glutathione peroxidase activity of inorganic selenium and seleno-DL-cysteine". Experientia. 31 (7): 769–770. doi:10.1007/BF01938453. ISSN 0014-4754. PMID 1140308. S2CID 26234261.
  14. ^ Ohno, S. (January 1977). "The original function of MHC antigens as the general plasma membrane anchorage site of organogenesis-directing proteins". Immunological Reviews. 33: 59–69. doi:10.1111/j.1600-065X.1977.tb00362.x. ISSN 0105-2896. PMID 66186. S2CID 45992817.
  15. ^ Beutler, B.; Nagai, Y.; Ohno, S.; Klein, G.; Shapiro, I. M. (March 1978). "The HLA-dependent expression of testis- organizing H-Y antigen by human male cells". Cell. 13 (3): 509–513. doi:10.1016/0092-8674(78)90324-0. ISSN 0092-8674. PMID 77737. S2CID 33827976.
  16. ^ Easton, John (October 10, 2011). "Alumnus Bruce Beutler, MD'81, to receive 2011 Nobel Prize in Medicine". uchicago news. Retrieved March 9, 2023.
  17. ^ "Bruce Beutler, MD". The American Society for Clinical Investigation. Retrieved October 18, 2023.
  18. ^ a b c Beutler, B.; Greenwald, D.; Hulmes, J. D.; Chang, M.; Pan, Y. C.; Mathison, J.; Ulevitch, R.; Cerami, A. (August 1, 1985). "Identity of tumour necrosis factor and the macrophage-secreted factor cachectin". Nature. 316 (6028): 552–554. Bibcode:1985Natur.316..552B. doi:10.1038/316552a0. ISSN 0028-0836. PMID 2993897. S2CID 4339006.
  19. ^ a b Beutler, B.; Mahoney, J.; Le Trang, N.; Pekala, P.; Cerami, A. (May 1, 1985). "Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells". The Journal of Experimental Medicine. 161 (5): 984–995. doi:10.1084/jem.161.5.984. ISSN 0022-1007. PMC 2187615. PMID 3872925.
  20. ^ Aggarwal, B. B.; Kohr, W. J.; Hass, P. E.; Moffat, B.; Spencer, S. A.; Henzel, W. J.; Bringman, T. S.; Nedwin, G. E.; Goeddel, D. V.; Harkins, R. N. (February 25, 1985). "Human tumor necrosis factor. Production, purification, and characterization". The Journal of Biological Chemistry. 260 (4): 2345–2354. doi:10.1016/S0021-9258(18)89560-6. ISSN 0021-9258. PMID 3871770.
  21. ^ a b c Beutler, B.; Milsark, I. W.; Cerami, A. C. (August 30, 1985). "Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin". Science. 229 (4716): 869–871. Bibcode:1985Sci...229..869B. doi:10.1126/science.3895437. ISSN 0036-8075. PMID 3895437.
  22. ^ Dayer, J. M.; Beutler, B.; Cerami, A. (December 1, 1985). "Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts". The Journal of Experimental Medicine. 162 (6): 2163–2168. doi:10.1084/jem.162.6.2163. ISSN 0022-1007. PMC 2187983. PMID 2999289.
  23. ^ Feldmann, M.; Brennan, F. M.; Maini, R. N. (1996). "Role of cytokines in rheumatoid arthritis". Annual Review of Immunology. 14: 397–440. doi:10.1146/annurev.immunol.14.1.397. ISSN 0732-0582. PMID 8717520.
  24. ^ Engelmann, H.; Novick, D.; Wallach, D. (January 25, 1990). "Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors". The Journal of Biological Chemistry. 265 (3): 1531–1536. doi:10.1016/S0021-9258(19)40049-5. ISSN 0021-9258. PMID 2153136.
  25. ^ Loetscher, H.; Pan, Y. C.; Lahm, H. W.; Gentz, R.; Brockhaus, M.; Tabuchi, H.; Lesslauer, W. (April 20, 1990). "Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor". Cell. 61 (2): 351–359. doi:10.1016/0092-8674(90)90815-v. ISSN 0092-8674. PMID 2158862. S2CID 42245440.
  26. ^ Nophar, Y.; Kemper, O.; Brakebusch, C.; Englemann, H.; Zwang, R.; Aderka, D.; Holtmann, H.; Wallach, D. (October 1, 1990). "Soluble forms of tumor necrosis factor receptors (TNF-Rs). The cDNA for the type I TNF-R, cloned using amino acid sequence data of its soluble form, encodes both the cell surface and a soluble form of the receptor". The EMBO Journal. 9 (10): 3269–3278. doi:10.1002/j.1460-2075.1990.tb07526.x. ISSN 0261-4189. PMC 552060. PMID 1698610.
  27. ^ Schall, T. J.; Lewis, M.; Koller, K. J.; Lee, A.; Rice, G. C.; Wong, G. H.; Gatanaga, T.; Granger, G. A.; Lentz, R.; Raab, H. (April 20, 1990). "Molecular cloning and expression of a receptor for human tumor necrosis factor". Cell. 61 (2): 361–370. doi:10.1016/0092-8674(90)90816-w. ISSN 0092-8674. PMID 2158863. S2CID 36187863.
  28. ^ Smith, C. A.; Davis, T.; Anderson, D.; Solam, L.; Beckmann, M. P.; Jerzy, R.; Dower, S. K.; Cosman, D.; Goodwin, R. G. (May 25, 1990). "A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins". Science. 248 (4958): 1019–1023. Bibcode:1990Sci...248.1019S. doi:10.1126/science.2160731. ISSN 0036-8075. PMID 2160731.
  29. ^ Poltorak, A.; Peppel, K.; Beutler, B. (February 28, 1994). "Receptor-mediated label-transfer assay (RELAY): a novel method for the detection of plasma tumor necrosis factor at attomolar concentrations". Journal of Immunological Methods. 169 (1): 93–99. doi:10.1016/0022-1759(94)90128-7. ISSN 0022-1759. PMID 8133076.
  30. ^ a b Peppel, K.; Crawford, D.; Beutler, B. (December 1, 1991). "A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity". The Journal of Experimental Medicine. 174 (6): 1483–1489. doi:10.1084/jem.174.6.1483. ISSN 0022-1007. PMC 2119031. PMID 1660525.
  31. ^ Gardner, Jonathan (November 1, 2021). "A three-decade monopoly: how Amgen built a patent thicket around its top-selling drug | BioPharma Dive". BioPharma Dive. Retrieved March 9, 2023.
  32. ^ Beutler, B.; Poltorak, A. (July 2001). "Sepsis and evolution of the innate immune response". Critical Care Medicine. 29 (7 Suppl): S2–6, discussion S6–7. doi:10.1097/00003246-200107001-00002. ISSN 0090-3493. PMID 11445725.
  33. ^ Beutler, Bruce (1988). "Orchestration of septic shock by cytokines: the role of cachectin (tumor necrosis factor)". In Roth, B. (ed.). Molecular and Cellular Mechanisms of Septic Shock. New York: Alan R. Liss, Inc. pp. 219–235.
  34. ^ Beutler B (1992). "Cytokines in Shock: 1992". In Lamy M, Thijs LG (eds.). Mediators of Sepsis. Heidelberg: Springer Berlin. pp. 51–67.
  35. ^ Johnson, A. G.; Gaines, S.; Landy, M. (February 1, 1956). "Studies on the O antigen of Salmonella typhosa. V. Enhancement of antibody response to protein antigens by the purified lipopolysaccharide". The Journal of Experimental Medicine. 103 (2): 225–246. doi:10.1084/jem.103.2.225. ISSN 0022-1007. PMC 2136584. PMID 13286429.
  36. ^ a b Coutinho, A.; Meo, T. (December 1978). "Genetic basis for unresponsiveness to lipopolysaccharide in C57BL/10Cr mice". Immunogenetics. 7 (1): 17–24. doi:10.1007/BF01843983. ISSN 0093-7711. PMID 21302052. S2CID 29425605.
  37. ^ Watson, J.; Riblet, R. (November 1, 1974). "Genetic control of responses to bacterial lipopolysaccharides in mice. I. Evidence for a single gene that influences mitogenic and immunogenic respones [sic] to lipopolysaccharides". The Journal of Experimental Medicine. 140 (5): 1147–1161. doi:10.1084/jem.140.5.1147. ISSN 0022-1007. PMC 2139714. PMID 4138849.
  38. ^ Sultzer, B. M. (September 21, 1968). "Genetic control of leucocyte responses to endotoxin". Nature. 219 (5160): 1253–1254. Bibcode:1968Natur.219.1253S. doi:10.1038/2191253a0. ISSN 0028-0836. PMID 4877918. S2CID 41633552.
  39. ^ Beutler, Bruce (January 2002). "Toll-like receptors: how they work and what they do". Current Opinion in Hematology. 9 (1): 2–10. doi:10.1097/00062752-200201000-00002. ISSN 1065-6251. PMID 11753071. S2CID 36843541.
  40. ^ Du, X.; Poltorak, A.; Silva, M.; Beutler, B. (1999). "Analysis of Tlr4-mediated LPS signal transduction in macrophages by mutational modification of the receptor". Blood Cells, Molecules & Diseases. 25 (5–6): 328–338. doi:10.1006/bcmd.1999.0262. ISSN 1079-9796. PMID 10660480.
  41. ^ a b c Poltorak, A.; Ricciardi-Castagnoli, P.; Citterio, S.; Beutler, B. (February 29, 2000). "Physical contact between lipopolysaccharide and toll-like receptor 4 revealed by genetic complementation". Proceedings of the National Academy of Sciences of the United States of America. 97 (5): 2163–2167. Bibcode:2000PNAS...97.2163P. doi:10.1073/pnas.040565397. ISSN 0027-8424. PMC 15771. PMID 10681462.
  42. ^ Shimazu, R.; Akashi, S.; Ogata, H.; Nagai, Y.; Fukudome, K.; Miyake, K.; Kimoto, M. (June 7, 1999). "MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4". The Journal of Experimental Medicine. 189 (11): 1777–1782. doi:10.1084/jem.189.11.1777. ISSN 0022-1007. PMC 2193086. PMID 10359581.
  43. ^ Park, Beom Seok; Song, Dong Hyun; Kim, Ho Min; Choi, Byong-Seok; Lee, Hayyoung; Lee, Jie-Oh (April 30, 2009). "The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex". Nature. 458 (7242): 1191–1195. Bibcode:2009Natur.458.1191P. doi:10.1038/nature07830. ISSN 1476-4687. PMID 19252480. S2CID 4396446.
  44. ^ Lemaitre, B.; Nicolas, E.; Michaut, L.; Reichhart, J. M.; Hoffmann, J. A. (September 20, 1996). "The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults". Cell. 86 (6): 973–983. doi:10.1016/s0092-8674(00)80172-5. ISSN 0092-8674. PMID 8808632. S2CID 10736743.
  45. ^ Medzhitov, R.; Preston-Hurlburt, P.; Janeway, C. A. (July 24, 1997). "A human homologue of the Drosophila Toll protein signals activation of adaptive immunity". Nature. 388 (6640): 394–397. doi:10.1038/41131. ISSN 0028-0836. PMID 9237759. S2CID 4311321.
  46. ^ Kirschning, C. J.; Wesche, H.; Merrill Ayres, T.; Rothe, M. (December 7, 1998). "Human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide". The Journal of Experimental Medicine. 188 (11): 2091–2097. doi:10.1084/jem.188.11.2091. ISSN 0022-1007. PMC 2212382. PMID 9841923.
  47. ^ Yang, R. B.; Mark, M. R.; Gray, A.; Huang, A.; Xie, M. H.; Zhang, M.; Goddard, A.; Wood, W. I.; Gurney, A. L.; Godowski, P. J. (September 17, 1998). "Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling". Nature. 395 (6699): 284–288. Bibcode:1998Natur.395..284Y. doi:10.1038/26239. ISSN 0028-0836. PMID 9751057. S2CID 4422827.
  48. ^ Beutler, B.; Poltorak, A. (June 2000). "Positional cloning of Lps, and the general role of toll-like receptors in the innate immune response". European Cytokine Network. 11 (2): 143–152. ISSN 1148-5493. PMID 10903793.
  49. ^ Christensen, Sean R.; Shupe, Jonathan; Nickerson, Kevin; Kashgarian, Michael; Flavell, Richard A.; Shlomchik, Mark J. (September 2006). "Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus". Immunity. 25 (3): 417–428. doi:10.1016/j.immuni.2006.07.013. ISSN 1074-7613. PMID 16973389.
  50. ^ Brown, Grant J.; Cañete, Pablo F.; Wang, Hao; Medhavy, Arti; Bones, Josiah; Roco, Jonathan A.; He, Yuke; Qin, Yuting; Cappello, Jean; Ellyard, Julia I.; Bassett, Katharine; Shen, Qian; Burgio, Gaetan; Zhang, Yaoyuan; Turnbull, Cynthia (May 2022). "TLR7 gain-of-function genetic variation causes human lupus". Nature. 605 (7909): 349–356. Bibcode:2022Natur.605..349B. doi:10.1038/s41586-022-04642-z. ISSN 1476-4687. PMC 9095492. PMID 35477763.
  51. ^ Leibler, Claire; John, Shinu; Elsner, Rebecca A.; Thomas, Kayla B.; Smita, Shuchi; Joachim, Stephen; Levack, Russell C.; Callahan, Derrick J.; Gordon, Rachael A.; Bastacky, Sheldon; Fukui, Ryutaro; Miyake, Kensuke; Gingras, Sebastien; Nickerson, Kevin M.; Shlomchik, Mark J. (October 2022). "Genetic dissection of TLR9 reveals complex regulatory and cryptic proinflammatory roles in mouse lupus". Nature Immunology. 23 (10): 1457–1469. doi:10.1038/s41590-022-01310-2. ISSN 1529-2916. PMC 9561083. PMID 36151396.
  52. ^ a b Baccala, Roberto; Gonzalez-Quintial, Rosana; Blasius, Amanda L.; Rimann, Ivo; Ozato, Keiko; Kono, Dwight H.; Beutler, Bruce; Theofilopoulos, Argyrios N. (February 19, 2013). "Essential requirement for IRF8 and SLC15A4 implicates plasmacytoid dendritic cells in the pathogenesis of lupus". Proceedings of the National Academy of Sciences of the United States of America. 110 (8): 2940–2945. Bibcode:2013PNAS..110.2940B. doi:10.1073/pnas.1222798110. ISSN 1091-6490. PMC 3581947. PMID 23382217.
  53. ^ Kono, Dwight H.; Haraldsson, M. Katarina; Lawson, Brian R.; Pollard, K. Michael; Koh, Yi Ting; Du, Xin; Arnold, Carrie N.; Baccala, Roberto; Silverman, Gregg J.; Beutler, Bruce A.; Theofilopoulos, Argyrios N. (July 21, 2009). "Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor autoantibodies in lupus". Proceedings of the National Academy of Sciences of the United States of America. 106 (29): 12061–12066. Bibcode:2009PNAS..10612061K. doi:10.1073/pnas.0905441106. ISSN 1091-6490. PMC 2715524. PMID 19574451.
  54. ^ Lau, Christina M.; Broughton, Courtney; Tabor, Abigail S.; Akira, Shizuo; Flavell, Richard A.; Mamula, Mark J.; Christensen, Sean R.; Shlomchik, Mark J.; Viglianti, Gregory A.; Rifkin, Ian R.; Marshak-Rothstein, Ann (November 7, 2005). "RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement". The Journal of Experimental Medicine. 202 (9): 1171–1177. doi:10.1084/jem.20050630. ISSN 0022-1007. PMC 2213226. PMID 16260486.
  55. ^ Leadbetter, Elizabeth A.; Rifkin, Ian R.; Hohlbaum, Andreas M.; Beaudette, Britte C.; Shlomchik, Mark J.; Marshak-Rothstein, Ann (April 11, 2002). "Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors". Nature. 416 (6881): 603–607. doi:10.1038/416603a. ISSN 0028-0836. PMID 11948342. S2CID 4370544.
  56. ^ Viglianti, Gregory A.; Lau, Christina M.; Hanley, Timothy M.; Miko, Benjamin A.; Shlomchik, Mark J.; Marshak-Rothstein, Ann (December 2003). "Activation of autoreactive B cells by CpG dsDNA". Immunity. 19 (6): 837–847. doi:10.1016/s1074-7613(03)00323-6. ISSN 1074-7613. PMID 14670301.
  57. ^ Beutler, Bruce; Du, Xin; Xia, Yu (July 2007). "Precis on forward genetics in mice". Nature Immunology. 8 (7): 659–664. doi:10.1038/ni0707-659. ISSN 1529-2908. PMID 17579639. S2CID 28309476.
  58. ^ a b Hoebe, K.; Du, X.; Georgel, P.; Janssen, E.; Tabeta, K.; Kim, S. O.; Goode, J.; Lin, P.; Mann, N.; Mudd, S.; Crozat, K.; Sovath, S.; Han, J.; Beutler, B. (August 14, 2003). "Identification of Lps2 as a key transducer of MyD88-independent TIR signalling". Nature. 424 (6950): 743–748. Bibcode:2003Natur.424..743H. doi:10.1038/nature01889. ISSN 1476-4687. PMID 12872135. S2CID 15608748.
  59. ^ Hoebe, Kasper; Georgel, Philippe; Rutschmann, Sophie; Du, Xin; Mudd, Suzanne; Crozat, Karine; Sovath, Sosathya; Shamel, Louis; Hartung, Thomas; Zähringer, Ulrich; Beutler, Bruce (February 3, 2005). "CD36 is a sensor of diacylglycerides". Nature. 433 (7025): 523–527. Bibcode:2005Natur.433..523H. doi:10.1038/nature03253. ISSN 1476-4687. PMID 15690042. S2CID 4406318.
  60. ^ a b Tabeta, Koichi; Hoebe, Kasper; Janssen, Edith M.; Du, Xin; Georgel, Philippe; Crozat, Karine; Mudd, Suzanne; Mann, Navjiwan; Sovath, Sosathya; Goode, Jason; Shamel, Louis; Herskovits, Anat A.; Portnoy, Daniel A.; Cooke, Michael; Tarantino, Lisa M. (January 15, 2006). "The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9". Nature Immunology. 7 (2): 156–164. doi:10.1038/ni1297. ISSN 1529-2908. PMID 16415873. S2CID 33401155.
  61. ^ Croker, Ben A.; Lawson, Brian R.; Rutschmann, Sophie; Berger, Michael; Eidenschenk, Celine; Blasius, Amanda L.; Moresco, Eva Marie Y.; Sovath, Sosathya; Cengia, Louise; Shultz, Leonard D.; Theofilopoulos, Argyrios N.; Pettersson, Sven; Beutler, Bruce Alan (September 30, 2008). "Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger". Proceedings of the National Academy of Sciences of the United States of America. 105 (39): 15028–15033. Bibcode:2008PNAS..10515028C. doi:10.1073/pnas.0806619105. ISSN 1091-6490. PMC 2567487. PMID 18806225.
  62. ^ Shi, Hexin; Wang, Ying; Li, Xiaohong; Zhan, Xiaoming; Tang, Miao; Fina, Maggy; Su, Lijing; Pratt, David; Bu, Chun Hui; Hildebrand, Sara; Lyon, Stephen; Scott, Lindsay; Quan, Jiexia; Sun, Qihua; Russell, Jamie (December 7, 2015). "NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component". Nature Immunology. 17 (3): 250–258. doi:10.1038/ni.3333. ISSN 1529-2916. PMC 4862588. PMID 26642356.
  63. ^ Sun, Lei; Jiang, Zhengfan; Acosta-Rodriguez, Victoria A.; Berger, Michael; Du, Xin; Choi, Jin Huk; Wang, Jianhui; Wang, Kuan-Wen; Kilaru, Gokhul K.; Mohawk, Jennifer A.; Quan, Jiexia; Scott, Lindsay; Hildebrand, Sara; Li, Xiaohong; Tang, Miao (November 6, 2017). "HCFC2 is needed for IRF1- and IRF2-dependent Tlr3 transcription and for survival during viral infections". The Journal of Experimental Medicine. 214 (11): 3263–3277. doi:10.1084/jem.20161630. ISSN 1540-9538. PMC 5679162. PMID 28970238.
  64. ^ Shi, Hexin; Sun, Lei; Wang, Ying; Liu, Aijie; Zhan, Xiaoming; Li, Xiaohong; Tang, Miao; Anderton, Priscilla; Hildebrand, Sara; Quan, Jiexia; Ludwig, Sara; Moresco, Eva Marie Y.; Beutler, Bruce (March 2, 2021). "N4BP1 negatively regulates NF-κB by binding and inhibiting NEMO oligomerization". Nature Communications. 12 (1): 1379. Bibcode:2021NatCo..12.1379S. doi:10.1038/s41467-021-21711-5. ISSN 2041-1723. PMC 7925594. PMID 33654074.
  65. ^ Kim, You-Me; Brinkmann, Melanie M.; Paquet, Marie-Eve; Ploegh, Hidde L. (March 13, 2008). "UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes". Nature. 452 (7184): 234–238. Bibcode:2008Natur.452..234K. doi:10.1038/nature06726. ISSN 1476-4687. PMID 18305481. S2CID 4397023.
  66. ^ a b Casrouge, Armanda; Zhang, Shen-Ying; Eidenschenk, Céline; Jouanguy, Emmanuelle; Puel, Anne; Yang, Kun; Alcais, Alexandre; Picard, Capucine; Mahfoufi, Nora; Nicolas, Nathalie; Lorenzo, Lazaro; Plancoulaine, Sabine; Sénéchal, Brigitte; Geissmann, Frédéric; Tabeta, Koichi (October 13, 2006). "Herpes simplex virus encephalitis in human UNC-93B deficiency". Science. 314 (5797): 308–312. Bibcode:2006Sci...314..308C. doi:10.1126/science.1128346. ISSN 1095-9203. PMID 16973841. S2CID 12501759.
  67. ^ Blasius, Amanda L.; Arnold, Carrie N.; Georgel, Philippe; Rutschmann, Sophie; Xia, Yu; Lin, Pei; Ross, Charles; Li, Xiaohong; Smart, Nora G.; Beutler, Bruce (November 16, 2010). "Slc15a4, AP-3, and Hermansky-Pudlak syndrome proteins are required for Toll-like receptor signaling in plasmacytoid dendritic cells". Proceedings of the National Academy of Sciences of the United States of America. 107 (46): 19973–19978. Bibcode:2010PNAS..10719973B. doi:10.1073/pnas.1014051107. ISSN 1091-6490. PMC 2993408. PMID 21045126.
  68. ^ Lazar, Daniel C.; Wang, Wesley W.; Chiu, Tzu-Yuan; Li, Weichao; Jadhav, Appaso M.; Wozniak, Jacob M.; Gazaniga, Nathalia; Theofilopoulos, Argyrios N.; Teijaro, John R.; Parker, Christopher G. (October 7, 2022). "Chemoproteomics-guided development of SLC15A4 inhibitors with anti-inflammatory activity". doi:10.1101/2022.10.07.511216. S2CID 252820006. {{cite journal}}: Cite journal requires |journal= (help)
  69. ^ Beutler, Bruce; Crozat, Karine; Koziol, James A.; Georgel, Philippe (February 2005). "Genetic dissection of innate immunity to infection: the mouse cytomegalovirus model". Current Opinion in Immunology. 17 (1): 36–43. doi:10.1016/j.coi.2004.11.004. ISSN 0952-7915. PMID 15653308.
  70. ^ Beutler, Bruce; Eidenschenk, Celine; Crozat, Karine; Imler, Jean-Luc; Takeuchi, Osamu; Hoffmann, Jules A.; Akira, Shizuo (October 2007). "Genetic analysis of resistance to viral infection". Nature Reviews. Immunology. 7 (10): 753–766. doi:10.1038/nri2174. ISSN 1474-1741. PMID 17893693. S2CID 37705652.
  71. ^ Croker, B.; Crozat, K.; Berger, M.; Xia, Y.; Sovath, S.; Schaffer, L.; Eleftherianos, I.; Imler, J. L.; Beutler, B. (2007). "ATP-sensitive potassium channels mediate survival during infection in mammals and insects". Nature Genetics. 39 (12): 1453–1460. doi:10.1038/ng.2007.25. PMID 18026101. S2CID 41183715.
  72. ^ Brandl, Katharina; Rutschmann, Sophie; Li, Xiaohong; Du, Xin; Xiao, Nengming; Schnabl, Bernd; Brenner, David A.; Beutler, Bruce (March 3, 2009). "Enhanced sensitivity to DSS colitis caused by a hypomorphic Mbtps1 mutation disrupting the ATF6-driven unfolded protein response". Proceedings of the National Academy of Sciences of the United States of America. 106 (9): 3300–3305. Bibcode:2009PNAS..106.3300B. doi:10.1073/pnas.0813036106. ISSN 1091-6490. PMC 2651297. PMID 19202076.
  73. ^ Brandl, Katharina; Sun, Lei; Neppl, Christina; Siggs, Owen M.; Le Gall, Sylvain M.; Tomisato, Wataru; Li, Xiaohong; Du, Xin; Maennel, Daniela N.; Blobel, Carl P.; Beutler, Bruce (November 16, 2010). "MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands". Proceedings of the National Academy of Sciences of the United States of America. 107 (46): 19967–19972. Bibcode:2010PNAS..10719967B. doi:10.1073/pnas.1014669107. ISSN 1091-6490. PMC 2993336. PMID 21041656.
  74. ^ Brandl, Katharina; Tomisato, Wataru; Li, Xiaohong; Neppl, Christina; Pirie, Elaine; Falk, Werner; Xia, Yu; Moresco, Eva Marie Y.; Baccala, Roberto; Theofilopoulos, Argyrios N.; Schnabl, Bernd; Beutler, Bruce (July 31, 2012). "Yip1 domain family, member 6 (Yipf6) mutation induces spontaneous intestinal inflammation in mice". Proceedings of the National Academy of Sciences of the United States of America. 109 (31): 12650–12655. Bibcode:2012PNAS..10912650B. doi:10.1073/pnas.1210366109. ISSN 1091-6490. PMC 3412000. PMID 22802641.
  75. ^ McAlpine, William; Sun, Lei; Wang, Kuan-Wen; Liu, Aijie; Jain, Ruchi; San Miguel, Miguel; Wang, Jianhui; Zhang, Zhao; Hayse, Braden; McAlpine, Sarah Grace; Choi, Jin Huk; Zhong, Xue; Ludwig, Sara; Russell, Jamie; Zhan, Xiaoming (December 4, 2018). "Excessive endosomal TLR signaling causes inflammatory disease in mice with defective SMCR8-WDR41-C9ORF72 complex function". Proceedings of the National Academy of Sciences of the United States of America. 115 (49): E11523–E11531. Bibcode:2018PNAS..11511523M. doi:10.1073/pnas.1814753115. ISSN 1091-6490. PMC 6298088. PMID 30442666.
  76. ^ McAlpine, William; Wang, Kuan-Wen; Choi, Jin Huk; San Miguel, Miguel; McAlpine, Sarah Grace; Russell, Jamie; Ludwig, Sara; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Choi, Mihwa; Wang, Tao; Bu, Chun Hui; Murray, Anne R.; Moresco, Eva Marie Y. (September 27, 2018). "The class I myosin MYO1D binds to lipid and protects against colitis". Disease Models & Mechanisms. 11 (9): dmm035923. doi:10.1242/dmm.035923. ISSN 1754-8411. PMC 6176994. PMID 30279225.
  77. ^ Wang, Kuan-Wen; Zhan, Xiaoming; McAlpine, William; Zhang, Zhao; Choi, Jin Huk; Shi, Hexin; Misawa, Takuma; Yue, Tao; Zhang, Duanwu; Wang, Ying; Ludwig, Sara; Russell, Jamie; Tang, Miao; Li, Xiaohong; Murray, Anne R. (June 4, 2019). "Enhanced susceptibility to chemically induced colitis caused by excessive endosomal TLR signaling in LRBA-deficient mice". Proceedings of the National Academy of Sciences of the United States of America. 116 (23): 11380–11389. Bibcode:2019PNAS..11611380W. doi:10.1073/pnas.1901407116. ISSN 1091-6490. PMC 6561264. PMID 31097594.
  78. ^ Turer, Emre; McAlpine, William; Wang, Kuan-Wen; Lu, Tianshi; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Murray, Anne R.; Beutler, Bruce (February 14, 2017). "Creatine maintains intestinal homeostasis and protects against colitis". Proceedings of the National Academy of Sciences of the United States of America. 114 (7): E1273–E1281. Bibcode:2017PNAS..114E1273T. doi:10.1073/pnas.1621400114. ISSN 1091-6490. PMC 5321020. PMID 28137860.
  79. ^ SoRelle, Jeffrey A.; Chen, Zhe; Wang, Jianhui; Yue, Tao; Choi, Jin Huk; Wang, Kuan-Wen; Zhong, Xue; Hildebrand, Sara; Russell, Jamie; Scott, Lindsay; Xu, Darui; Zhan, Xiaowei; Bu, Chun Hui; Wang, Tao; Choi, Mihwa (April 2021). "Dominant atopy risk mutations identified by mouse forward genetic analysis". Allergy. 76 (4): 1095–1108. doi:10.1111/all.14564. ISSN 1398-9995. PMC 7889751. PMID 32810290.
  80. ^ a b Chatenoud, Lucienne; Marquet, Cindy; Valette, Fabrice; Scott, Lindsay; Quan, Jiexia; Bu, Chun Hui; Hildebrand, Sara; Moresco, Eva Marie Y.; Bach, Jean-François; Beutler, Bruce (June 1, 2022). "Modulation of autoimmune diabetes by N-ethyl-N-nitrosourea- induced mutations in non-obese diabetic mice". Disease Models & Mechanisms. 15 (6): dmm049484. doi:10.1242/dmm.049484. ISSN 1754-8411. PMC 9178510. PMID 35502705.
  81. ^ a b Foray, Anne-Perrine; Candon, Sophie; Hildebrand, Sara; Marquet, Cindy; Valette, Fabrice; Pecquet, Coralie; Lemoine, Sebastien; Langa-Vives, Francina; Dumas, Michael; Hu, Peipei; Santamaria, Pere; You, Sylvaine; Lyon, Stephen; Scott, Lindsay; Bu, Chun Hui (November 23, 2021). "De novo germline mutation in the dual specificity phosphatase 10 gene accelerates autoimmune diabetes". Proceedings of the National Academy of Sciences of the United States of America. 118 (47): e2112032118. Bibcode:2021PNAS..11812032F. doi:10.1073/pnas.2112032118. ISSN 1091-6490. PMC 8617500. PMID 34782469.
  82. ^ a b c Zhang, Zhao; Turer, Emre; Li, Xiaohong; Zhan, Xiaoming; Choi, Mihwa; Tang, Miao; Press, Amanda; Smith, Steven R.; Divoux, Adeline; Moresco, Eva Marie Y.; Beutler, Bruce (October 18, 2016). "Insulin resistance and diabetes caused by genetic or diet-induced KBTBD2 deficiency in mice". Proceedings of the National Academy of Sciences of the United States of America. 113 (42): E6418–E6426. Bibcode:2016PNAS..113E6418Z. doi:10.1073/pnas.1614467113. ISSN 1091-6490. PMC 5081616. PMID 27708159.
  83. ^ Turer, Emre E.; San Miguel, Miguel; Wang, Kuan-Wen; McAlpine, William; Ou, Feiya; Li, Xiaohong; Tang, Miao; Zang, Zhao; Wang, Jianhui; Hayse, Braden; Evers, Bret; Zhan, Xiaoming; Russell, Jamie; Beutler, Bruce (December 18, 2018). "A viable hypomorphic Arnt2 mutation causes hyperphagic obesity, diabetes and hepatic steatosis". Disease Models & Mechanisms. 11 (12): dmm035451. doi:10.1242/dmm.035451. ISSN 1754-8411. PMC 6307907. PMID 30563851.
  84. ^ a b c Zhang, Zhao; Jiang, Yiao; Su, Lijing; Ludwig, Sara; Zhang, Xuechun; Tang, Miao; Li, Xiaohong; Anderton, Priscilla; Zhan, Xiaoming; Choi, Mihwa; Russell, Jamie; Bu, Chun-Hui; Lyon, Stephen; Xu, Darui; Hildebrand, Sara (November 1, 2022). "Obesity caused by an OVOL2 mutation reveals dual roles of OVOL2 in promoting thermogenesis and limiting white adipogenesis". Cell Metabolism. 34 (11): 1860–1874.e4. doi:10.1016/j.cmet.2022.09.018. ISSN 1932-7420. PMC 9633419. PMID 36228616.
  85. ^ a b Berger, Michael; Krebs, Philippe; Crozat, Karine; Li, Xiaohong; Croker, Ben A.; Siggs, Owen M.; Popkin, Daniel; Du, Xin; Lawson, Brian R.; Theofilopoulos, Argyrios N.; Xia, Yu; Khovananth, Kevin; Moresco, Eva Marie; Satoh, Takashi; Takeuchi, Osamu (April 2010). "An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence". Nature Immunology. 11 (4): 335–343. doi:10.1038/ni.1847. ISSN 1529-2916. PMC 2861894. PMID 20190759.
  86. ^ Siggs, Owen M.; Arnold, Carrie N.; Huber, Christoph; Pirie, Elaine; Xia, Yu; Lin, Pei; Nemazee, David; Beutler, Bruce (May 2011). "The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow". Nature Immunology. 12 (5): 434–440. doi:10.1038/ni.2012. ISSN 1529-2916. PMC 3079768. PMID 21423172.
  87. ^ Siggs, Owen M.; Li, Xiaohong; Xia, Yu; Beutler, Bruce (January 16, 2012). "ZBTB1 is a determinant of lymphoid development". The Journal of Experimental Medicine. 209 (1): 19–27. doi:10.1084/jem.20112084. ISSN 1540-9538. PMC 3260866. PMID 22201126.
  88. ^ a b Choi, Jin Huk; Han, Jonghee; Theodoropoulos, Panayotis C.; Zhong, Xue; Wang, Jianhui; Medler, Dawson; Ludwig, Sara; Zhan, Xiaoming; Li, Xiaohong; Tang, Miao; Gallagher, Thomas; Yu, Gang; Beutler, Bruce (March 3, 2020). "Essential requirement for nicastrin in marginal zone and B-1 B cell development". Proceedings of the National Academy of Sciences of the United States of America. 117 (9): 4894–4901. Bibcode:2020PNAS..117.4894C. doi:10.1073/pnas.1916645117. ISSN 1091-6490. PMC 7060662. PMID 32071239.
  89. ^ a b Choi, Jin Huk; Zhong, Xue; McAlpine, William; Liao, Tzu-Chieh; Zhang, Duanwu; Fang, Beibei; Russell, Jamie; Ludwig, Sara; Nair-Gill, Evan; Zhang, Zhao; Wang, Kuan-Wen; Misawa, Takuma; Zhan, Xiaoming; Choi, Mihwa; Wang, Tao (May 10, 2019). "LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling". Science. 364 (6440): eaau0812. doi:10.1126/science.aau0812. ISSN 1095-9203. PMC 7206793. PMID 31073040.
  90. ^ a b Choi, Jin Huk; Zhong, Xue; Zhang, Zhao; Su, Lijing; McAlpine, William; Misawa, Takuma; Liao, Tzu-Chieh; Zhan, Xiaoming; Russell, Jamie; Ludwig, Sara; Li, Xiaohong; Tang, Miao; Anderton, Priscilla; Moresco, Eva Marie Y.; Beutler, Bruce (April 6, 2020). "Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development". The Journal of Experimental Medicine. 217 (4): e20190006. doi:10.1084/jem.20190006. ISSN 1540-9538. PMC 7144532. PMID 31985756.
  91. ^ a b Zhang, Duanwu; Yue, Tao; Choi, Jin Huk; Nair-Gill, Evan; Zhong, Xue; Wang, Kuan-Wen; Zhan, Xiaoming; Li, Xiaohong; Choi, Mihwa; Tang, Miao; Quan, Jiexia; Hildebrand, Sara; Moresco, Eva Marie Y.; Beutler, Bruce (October 2019). "Syndromic immune disorder caused by a viable hypomorphic allele of spliceosome component Snrnp40". Nature Immunology. 20 (10): 1322–1334. doi:10.1038/s41590-019-0464-4. ISSN 1529-2916. PMC 7179765. PMID 31427773.
  92. ^ a b Zhong, Xue; Choi, Jin Huk; Hildebrand, Sara; Ludwig, Sara; Wang, Jianhui; Nair-Gill, Evan; Liao, Tzu-Chieh; Moresco, James J.; Liu, Aijie; Quan, Jiexia; Sun, Qihua; Zhang, Duanwu; Zhan, Xiaoming; Choi, Mihwa; Li, Xiaohong (May 3, 2022). "RNPS1 inhibits excessive tumor necrosis factor/tumor necrosis factor receptor signaling to support hematopoiesis in mice". Proceedings of the National Academy of Sciences of the United States of America. 119 (18): e2200128119. Bibcode:2022PNAS..11900128Z. doi:10.1073/pnas.2200128119. ISSN 1091-6490. PMC 9170173. PMID 35482923.
  93. ^ a b Zhong, Xue; Su, Lijing; Yang, Yi; Nair-Gill, Evan; Tang, Miao; Anderton, Priscilla; Li, Xiaohong; Wang, Jianhui; Zhan, Xiaoming; Tomchick, Diana R.; Brautigam, Chad A.; Moresco, Eva Marie Y.; Choi, Jin Huk; Beutler, Bruce (April 14, 2020). "Genetic and structural studies of RABL3 reveal an essential role in lymphoid development and function". Proceedings of the National Academy of Sciences of the United States of America. 117 (15): 8563–8572. Bibcode:2020PNAS..117.8563Z. doi:10.1073/pnas.2000703117. ISSN 1091-6490. PMC 7165429. PMID 32220963.
  94. ^ a b Misawa, Takuma; SoRelle, Jeffrey A.; Choi, Jin Huk; Yue, Tao; Wang, Kuan-Wen; McAlpine, William; Wang, Jianhui; Liu, Aijie; Tabeta, Koichi; Turer, Emre E.; Evers, Bret; Nair-Gill, Evan; Poddar, Subhajit; Su, Lijing; Ou, Feiya (January 24, 2020). "Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation". Science Immunology. 5 (43): eaaz0085. doi:10.1126/sciimmunol.aaz0085. ISSN 2470-9468. PMC 7278039. PMID 31980486.
  95. ^ Arnold, Carrie N.; Pirie, Elaine; Dosenovic, Pia; McInerney, Gerald M.; Xia, Yu; Wang, Nathaniel; Li, Xiaohong; Siggs, Owen M.; Karlsson Hedestam, Gunilla B.; Beutler, Bruce (July 31, 2012). "A forward genetic screen reveals roles for Nfkbid, Zeb1, and Ruvbl2 in humoral immunity". Proceedings of the National Academy of Sciences of the United States of America. 109 (31): 12286–12293. doi:10.1073/pnas.1209134109. ISSN 1091-6490. PMC 3411946. PMID 22761313.
  96. ^ Choi, Jin Huk; Wang, Kuan-Wen; Zhang, Duanwu; Zhan, Xiaowei; Wang, Tao; Bu, Chun-Hui; Behrendt, Cassie L.; Zeng, Ming; Wang, Ying; Misawa, Takuma; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Scott, Lindsay; Hildebrand, Sara (February 14, 2017). "IgD class switching is initiated by microbiota and limited to mucosa-associated lymphoid tissue in mice". Proceedings of the National Academy of Sciences of the United States of America. 114 (7): E1196–E1204. Bibcode:2017PNAS..114E1196C. doi:10.1073/pnas.1621258114. ISSN 1091-6490. PMC 5321007. PMID 28137874.
  97. ^ Yue, Tao; Zhan, Xiaoming; Zhang, Duanwu; Jain, Ruchi; Wang, Kuan-Wen; Choi, Jin Huk; Misawa, Takuma; Su, Lijing; Quan, Jiexia; Hildebrand, Sara; Xu, Darui; Li, Xiaohong; Turer, Emre; Sun, Lei; Moresco, Eva Marie Y. (May 14, 2021). "SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell-mediated immunity". Science. 372 (6543): eaba4220. doi:10.1126/science.aba4220. ISSN 1095-9203. PMC 8442736. PMID 33986151.
  98. ^ a b Nair-Gill, Evan; Bonora, Massimo; Zhong, Xue; Liu, Aijie; Miranda, Amber; Stewart, Nathan; Ludwig, Sara; Russell, Jamie; Gallagher, Thomas; Pinton, Paolo; Beutler, Bruce (May 3, 2021). "Calcium flux control by Pacs1-Wdr37 promotes lymphocyte quiescence and lymphoproliferative diseases". The EMBO Journal. 40 (9): e104888. doi:10.15252/embj.2020104888. ISSN 1460-2075. PMC 8090855. PMID 33630350.
  99. ^ Du, X.; She, E.; Gelbart, T.; Truksa, J.; Lee, P.; Xia, Y.; Khovananth, K.; Mudd, S.; Mann, N.; Moresco, E. M. Y.; Beutler, E.; Beutler, B. (2008). "The serine protease TMPRSS6 is required to sense iron deficiency". Science. 320 (5879): 1088–1092. Bibcode:2008Sci...320.1088D. doi:10.1126/science.1157121. PMC 2430097. PMID 18451267.
  100. ^ Du, X.; Schwander, M.; Moresco, E. M. Y.; Viviani, P.; Haller, C.; Hildebrand, M. S.; Pak, K.; Tarantino, L.; Roberts, A.; Richardson, H.; Koob, G.; Najmabadi, H.; Ryan, A. F.; Smith, R. J. H.; Muller, U.; Beutler, B. (2008). "A catechol-O-methyltransferase that is essential for auditory function in mice and humans". Proceedings of the National Academy of Sciences. 105 (38): 14609–14614. Bibcode:2008PNAS..10514609D. doi:10.1073/pnas.0807219105. PMC 2567147. PMID 18794526.
  101. ^ Blasius, Amanda L.; Brandl, Katharina; Crozat, Karine; Xia, Yu; Khovananth, Kevin; Krebs, Philippe; Smart, Nora G.; Zampolli, Antonella; Ruggeri, Zaverio M.; Beutler, Bruce A. (February 24, 2009). "Mice with mutations of Dock7 have generalized hypopigmentation and white-spotting but show normal neurological function". Proceedings of the National Academy of Sciences of the United States of America. 106 (8): 2706–2711. Bibcode:2009PNAS..106.2706B. doi:10.1073/pnas.0813208106. ISSN 1091-6490. PMC 2650330. PMID 19202056.
  102. ^ Rutschmann, Sophie; Crozat, Karine; Li, Xiaohong; Du, Xin; Hanselman, Jeffrey C.; Shigeoka, Alana A.; Brandl, Katharina; Popkin, Daniel L.; McKay, Dianne B.; Xia, Yu; Moresco, Eva Marie Y.; Beutler, Bruce (April 2012). "Hypopigmentation and maternal-zygotic embryonic lethality caused by a hypomorphic mbtps1 mutation in mice". G3: Genes, Genomes, Genetics. 2 (4): 499–504. doi:10.1534/g3.112.002196. ISSN 2160-1836. PMC 3337478. PMID 22540041.
  103. ^ Chen, Zhe; Holland, William; Shelton, John M.; Ali, Aktar; Zhan, Xiaoming; Won, Sungyong; Tomisato, Wataru; Liu, Chen; Li, Xiaohong; Moresco, Eva Marie Y.; Beutler, Bruce (May 20, 2014). "Mutation of mouse Samd4 causes leanness, myopathy, uncoupled mitochondrial respiration, and dysregulated mTORC1 signaling". Proceedings of the National Academy of Sciences of the United States of America. 111 (20): 7367–7372. Bibcode:2014PNAS..111.7367C. doi:10.1073/pnas.1406511111. ISSN 1091-6490. PMC 4034201. PMID 24799716.
  104. ^ a b Zhang, Zhao; Gallagher, Thomas; Scherer, Philipp E.; Beutler, Bruce (May 26, 2020). "Tissue-specific disruption of Kbtbd2 uncovers adipocyte-intrinsic and -extrinsic features of the teeny lipodystrophy syndrome". Proceedings of the National Academy of Sciences of the United States of America. 117 (21): 11829–11835. Bibcode:2020PNAS..11711829Z. doi:10.1073/pnas.2000118117. ISSN 1091-6490. PMC 7260979. PMID 32381739.
  105. ^ a b Zhang, Zhao; Xun, Yu; Rong, Shunxing; Yan, Lijuan; SoRelle, Jeffrey A.; Li, Xiaohong; Tang, Miao; Keller, Katie; Ludwig, Sara; Moresco, Eva Marie Y.; Beutler, Bruce (July 16, 2022). "Loss of immunity-related GTPase GM4951 leads to nonalcoholic fatty liver disease without obesity". Nature Communications. 13 (1): 4136. Bibcode:2022NatCo..13.4136Z. doi:10.1038/s41467-022-31812-4. ISSN 2041-1723. PMC 9288484. PMID 35842425.
  106. ^ Smyth, Ian; Du, Xin; Taylor, Martin S.; Justice, Monica J.; Beutler, Bruce; Jackson, Ian J. (September 14, 2004). "The extracellular matrix gene Frem1 is essential for the normal adhesion of the embryonic epidermis". Proceedings of the National Academy of Sciences of the United States of America. 101 (37): 13560–13565. Bibcode:2004PNAS..10113560S. doi:10.1073/pnas.0402760101. ISSN 0027-8424. PMC 518794. PMID 15345741.
  107. ^ Al-Fadhli, Fatima M.; Afqi, Manal; Sairafi, Mona Hamza; Almuntashri, Makki; Alharby, Essa; Alharbi, Ghadeer; Abdud Samad, Firoz; Hashmi, Jamil Amjad; Zaytuni, Dimah; Bahashwan, Ahmed A.; Choi, Jin Huk; Peake, Roy W. A.; Beutler, Bruce; Almontashiri, Naif A. M. (May 2021). "Biallelic loss of function variant in the unfolded protein response gene PDIA6 is associated with asphyxiating thoracic dystrophy and neonatal-onset diabetes". Clinical Genetics. 99 (5): 694–703. doi:10.1111/cge.13930. ISSN 1399-0004. PMID 33495992. S2CID 231710148.
  108. ^ Israel, Laura; Wang, Ying; Bulek, Katarzyna; Della Mina, Erika; Zhang, Zhao; Pedergnana, Vincent; Chrabieh, Maya; Lemmens, Nicole A.; Sancho-Shimizu, Vanessa; Descatoire, Marc; Lasseau, Théo; Israelsson, Elisabeth; Lorenzo, Lazaro; Yun, Ling; Belkadi, Aziz (February 23, 2017). "Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity". Cell. 168 (5): 789–800.e10. doi:10.1016/j.cell.2017.01.039. ISSN 1097-4172. PMC 5328639. PMID 28235196.
  109. ^ Melis, Maria Antonietta; Cau, Milena; Congiu, Rita; Sole, Gabriella; Barella, Susanna; Cao, Antonio; Westerman, Mark; Cazzola, Mario; Galanello, Renzo (October 2008). "A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron". Haematologica. 93 (10): 1473–1479. doi:10.3324/haematol.13342. ISSN 1592-8721. PMID 18603562. S2CID 23364362.
  110. ^ a b El Hayek, Lauretta; Tuncay, Islam Oguz; Nijem, Nadine; Russell, Jamie; Ludwig, Sara; Kaur, Kiran; Li, Xiaohong; Anderton, Priscilla; Tang, Miao; Gerard, Amanda; Heinze, Anja; Zacher, Pia; Alsaif, Hessa S.; Rad, Aboulfazl; Hassanpour, Kazem (December 22, 2020). "KDM5A mutations identified in autism spectrum disorder using forward genetics". eLife. 9: e56883. doi:10.7554/eLife.56883. ISSN 2050-084X. PMC 7755391. PMID 33350388.
  111. ^ a b Rios, Jonathan J.; Denton, Kristin; Yu, Hao; Manickam, Kandamurugu; Garner, Shannon; Russell, Jamie; Ludwig, Sara; Rosenfeld, Jill A.; Liu, Pengfei; Munch, Jake; Sucato, Daniel J.; Beutler, Bruce; Wise, Carol A. (June 1, 2021). "Saturation mutagenesis defines novel mouse models of severe spine deformity". Disease Models & Mechanisms. 14 (6): dmm048901. doi:10.1242/dmm.048901. ISSN 1754-8411. PMC 8246263. PMID 34142127.
  112. ^ a b Rios, Jonathan J.; Denton, Kristin; Russell, Jamie; Kozlitina, Julia; Ferreira, Carlos R.; Lewanda, Amy F.; Mayfield, Joshua E.; Moresco, Eva; Ludwig, Sara; Tang, Miao; Li, Xiaohong; Lyon, Stephen; Khanshour, Anas; Paria, Nandina; Khalid, Aysha (August 2021). "Germline Saturation Mutagenesis Induces Skeletal Phenotypes in Mice". Journal of Bone and Mineral Research. 36 (8): 1548–1565. doi:10.1002/jbmr.4323. ISSN 1523-4681. PMC 8862308. PMID 33905568.
  113. ^ Andrews, T. D.; Whittle, B.; Field, M. A.; Balakishnan, B.; Zhang, Y.; Shao, Y.; Cho, V.; Kirk, M.; Singh, M.; Xia, Y.; Hager, J.; Winslade, S.; Sjollema, G.; Beutler, B.; Enders, A. (May 2012). "Massively parallel sequencing of the mouse exome to accurately identify rare, induced mutations: an immediate source for thousands of new mouse models". Open Biology. 2 (5): 120061. doi:10.1098/rsob.120061. ISSN 2046-2441. PMC 3376740. PMID 22724066.
  114. ^ Bull, Katherine R.; Rimmer, Andrew J.; Siggs, Owen M.; Miosge, Lisa A.; Roots, Carla M.; Enders, Anselm; Bertram, Edward M.; Crockford, Tanya L.; Whittle, Belinda; Potter, Paul K.; Simon, Michelle M.; Mallon, Ann-Marie; Brown, Steve D. M.; Beutler, Bruce; Goodnow, Christopher C. (2013). "Unlocking the bottleneck in forward genetics using whole-genome sequencing and identity by descent to isolate causative mutations". PLOS Genetics. 9 (1): e1003219. doi:10.1371/journal.pgen.1003219. ISSN 1553-7404. PMC 3561070. PMID 23382690.
  115. ^ Xia, Yu; Won, Sungyong; Du, Xin; Lin, Pei; Ross, Charles; La Vine, Diantha; Wiltshire, Sean; Leiva, Gabriel; Vidal, Silvia M.; Whittle, Belinda; Goodnow, Christopher C.; Koziol, James; Moresco, Eva Marie Y.; Beutler, Bruce (December 2010). "Bulk segregation mapping of mutations in closely related strains of mice". Genetics. 186 (4): 1139–1146. doi:10.1534/genetics.110.121160. ISSN 1943-2631. PMC 2998299. PMID 20923982.
  116. ^ a b Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Lyon, Stephen; Pratt, David; Hildebrand, Sara; Choi, Jin Huk; Zhang, Zhao; Zeng, Ming; Wang, Kuan-wen; Turer, Emre; Chen, Zhe; Zhang, Duanwu; Yue, Tao; Wang, Ying (February 3, 2015). "Real-time resolution of point mutations that cause phenovariance in mice". Proceedings of the National Academy of Sciences of the United States of America. 112 (5): E440–449. Bibcode:2015PNAS..112E.440W. doi:10.1073/pnas.1423216112. ISSN 1091-6490. PMC 4321302. PMID 25605905.
  117. ^ Wang, Tao; Bu, Chun Hui; Hildebrand, Sara; Jia, Gaoxiang; Siggs, Owen M.; Lyon, Stephen; Pratt, David; Scott, Lindsay; Russell, Jamie; Ludwig, Sara; Murray, Anne R.; Moresco, Eva Marie Y.; Beutler, Bruce (January 30, 2018). "Probability of phenotypically detectable protein damage by ENU-induced mutations in the Mutagenetix database". Nature Communications. 9 (1): 441. Bibcode:2018NatCo...9..441W. doi:10.1038/s41467-017-02806-4. ISSN 2041-1723. PMC 5789985. PMID 29382827.
  118. ^ a b Xu, Darui; Lyon, Stephen; Bu, Chun Hui; Hildebrand, Sara; Choi, Jin Huk; Zhong, Xue; Liu, Aijie; Turer, Emre E.; Zhang, Zhao; Russell, Jamie; Ludwig, Sara; Mahrt, Elena; Nair-Gill, Evan; Shi, Hexin; Wang, Ying (July 13, 2021). "Thousands of induced germline mutations affecting immune cells identified by automated meiotic mapping coupled with machine learning". Proceedings of the National Academy of Sciences of the United States of America. 118 (28): e2106786118. Bibcode:2021PNAS..11806786X. doi:10.1073/pnas.2106786118. ISSN 1091-6490. PMC 8285956. PMID 34260399.
  119. ^ Chen, Bo; Aredo, Bogale; Ding, Yi; Zhong, Xin; Zhu, Yuanfei; Zhao, Cynthia X.; Kumar, Ashwani; Xing, Chao; Gautron, Laurent; Lyon, Stephen; Russell, Jamie; Li, Xiaohong; Tang, Miao; Anderton, Priscilla; Ludwig, Sara (June 9, 2020). "Forward genetic analysis using OCT screening identifies Sfxn3 mutations leading to progressive outer retinal degeneration in mice". Proceedings of the National Academy of Sciences of the United States of America. 117 (23): 12931–12942. Bibcode:2020PNAS..11712931C. doi:10.1073/pnas.1921224117. ISSN 1091-6490. PMC 7293615. PMID 32457148.
  120. ^ Wang, Yibing; Cao, Liqin; Lee, Chia-Ying; Matsuo, Tomohiko; Wu, Kejia; Asher, Greg; Tang, Lijun; Saitoh, Tsuyoshi; Russell, Jamie; Klewe-Nebenius, Daniela; Wang, Li; Soya, Shingo; Hasegawa, Emi; Chérasse, Yoan; Zhou, Jiamin (May 23, 2018). "Large-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors". Nature Communications. 9 (1): 2041. Bibcode:2018NatCo...9.2041W. doi:10.1038/s41467-018-04324-3. ISSN 2041-1723. PMC 5966455. PMID 29795268.
  121. ^ Morin, Matthew D.; Wang, Ying; Jones, Brian T.; Mifune, Yuto; Su, Lijing; Shi, Hexin; Moresco, Eva Marie Y.; Zhang, Hong; Beutler, Bruce; Boger, Dale L. (October 31, 2018). "Diprovocims: A New and Exceptionally Potent Class of Toll-like Receptor Agonists". Journal of the American Chemical Society. 140 (43): 14440–14454. doi:10.1021/jacs.8b09223. ISSN 1520-5126. PMC 6209530. PMID 30272974.
  122. ^ Morin, Matthew D.; Wang, Ying; Jones, Brian T.; Su, Lijing; Surakattula, Murali M. R. P.; Berger, Michael; Huang, Hua; Beutler, Elliot K.; Zhang, Hong; Beutler, Bruce; Boger, Dale L. (May 26, 2016). "Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists". Journal of Medicinal Chemistry. 59 (10): 4812–4830. doi:10.1021/acs.jmedchem.6b00177. ISSN 1520-4804. PMC 4882283. PMID 27050713.
  123. ^ Wang, Ying; Su, Lijing; Morin, Matthew D.; Jones, Brian T.; Mifune, Yuto; Shi, Hexin; Wang, Kuan-Wen; Zhan, Xiaoming; Liu, Aijie; Wang, Jianhui; Li, Xiaohong; Tang, Miao; Ludwig, Sara; Hildebrand, Sara; Zhou, Kejin (September 11, 2018). "Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in mice". Proceedings of the National Academy of Sciences of the United States of America. 115 (37): E8698–E8706. Bibcode:2018PNAS..115E8698W. doi:10.1073/pnas.1809232115. ISSN 1091-6490. PMC 6140543. PMID 30150374.
  124. ^ Wang, Ying; Su, Lijing; Morin, Matthew D.; Jones, Brian T.; Whitby, Landon R.; Surakattula, Murali M. R. P.; Huang, Hua; Shi, Hexin; Choi, Jin Huk; Wang, Kuan-wen; Moresco, Eva Marie Y.; Berger, Michael; Zhan, Xiaoming; Zhang, Hong; Boger, Dale L. (February 16, 2016). "TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS". Proceedings of the National Academy of Sciences of the United States of America. 113 (7): E884–893. Bibcode:2016PNAS..113E.884W. doi:10.1073/pnas.1525639113. ISSN 1091-6490. PMC 4763747. PMID 26831104.
  125. ^ Su, Lijing; Athamna, Muhammad; Wang, Ying; Wang, Junmei; Freudenberg, Marina; Yue, Tao; Wang, Jianhui; Moresco, Eva Marie Y.; He, Haoming; Zor, Tsaffrir; Beutler, Bruce (July 27, 2021). "Sulfatides are endogenous ligands for the TLR4-MD-2 complex". Proceedings of the National Academy of Sciences of the United States of America. 118 (30): e2105316118. Bibcode:2021PNAS..11805316S. doi:10.1073/pnas.2105316118. ISSN 1091-6490. PMC 8325290. PMID 34290146.
  126. ^ Su, Lijing; Wang, Ying; Wang, Junmei; Mifune, Yuto; Morin, Matthew D.; Jones, Brian T.; Moresco, Eva Marie Y.; Boger, Dale L.; Beutler, Bruce; Zhang, Hong (March 28, 2019). "Structural Basis of TLR2/TLR1 Activation by the Synthetic Agonist Diprovocim". Journal of Medicinal Chemistry. 62 (6): 2938–2949. doi:10.1021/acs.jmedchem.8b01583. ISSN 1520-4804. PMC 6537610. PMID 30829478.
  127. ^ Yang, Ming-Hsiu; Russell, Jamie L.; Mifune, Yuto; Wang, Ying; Shi, Hexin; Moresco, Eva Marie Y.; Siegwart, Daniel J.; Beutler, Bruce; Boger, Dale L. (July 14, 2022). "Next-Generation Diprovocims with Potent Human and Murine TLR1/TLR2 Agonist Activity That Activate the Innate and Adaptive Immune Response". Journal of Medicinal Chemistry. 65 (13): 9230–9252. doi:10.1021/acs.jmedchem.2c00419. ISSN 1520-4804. PMC 9283309. PMID 35767437.
  128. ^ Eric (April 24, 2009). "TSRI's Beutler shares America's largest prize in medicine". Del Mar Times. Retrieved March 9, 2023.
  129. ^ Kristoffer Furberg (March 20, 2015). . Universitetsavisa (in Norwegian). Archived from the original on July 14, 2018. Retrieved March 25, 2015.
  130. ^ "Umg, laurea honoris causa al Premio Nobel Bruce Alan Beutler". September 23, 2019.
  131. ^ Beutler, E. (February 1959). "The hemolytic effect of primaquine and related compounds: a review". Blood. 14 (2): 103–139. doi:10.1182/blood.V14.2.103.103. ISSN 0006-4971. PMID 13618370.
  132. ^ Beutler, Ernest (1971). Red Cell Metabolism: A Handbook of Biochemical Methods. New York: Grune and Stratton.
  133. ^ Beutler E (2006). "Disorders of red cells resulting from enzyme abnormalitites". In Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT (eds.). Williams Hematology. New York: McGraw-Hill. pp. 603–632.
  134. ^ Beutler, E (February 1961). "Hematology: Iron Metabolism". Annual Review of Medicine. 12 (1): 195–210. doi:10.1146/annurev.me.12.020161.001211. ISSN 0066-4219.
  135. ^ Beutler, Ernest (July 2006). "Lysosomal storage diseases: natural history and ethical and economic aspects". Molecular Genetics and Metabolism. 88 (3): 208–215. doi:10.1016/j.ymgme.2006.01.010. ISSN 1096-7192. PMID 16515872.
  136. ^ Beutler, E.; Blume, K. G.; Bross, K. J.; Chillar, R. K.; Ellington, O. B.; Fahey, J. L.; Farbstein, M. J.; Schmidt, G. M.; Spruce, W. E.; Turner, M. A. (1979). "Bone marrow transplantation as the treatment of choice for "good risk" adult patients with acute leukemia". Transactions of the Association of American Physicians. 92: 189–195. ISSN 0066-9458. PMID 398617.
  137. ^ Piro, L. D.; Carrera, C. J.; Carson, D. A.; Beutler, E. (April 19, 1990). "Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine". The New England Journal of Medicine. 322 (16): 1117–1121. doi:10.1056/NEJM199004193221605. ISSN 0028-4793. PMID 1969613.
  138. ^ Beutler, E.; Yeh, M.; Fairbanks, V. F. (January 15, 1962). "The normal human female as a mosaic of X-chromosome activity: studies using the gene for C-6-PD-deficiency as a marker". Proceedings of the National Academy of Sciences of the United States of America. 48 (1): 9–16. Bibcode:1962PNAS...48....9B. doi:10.1073/pnas.48.1.9. ISSN 0027-8424. PMC 285481. PMID 13868717.
  139. ^ Beutler, Bruce; Beutler, Ernest (December 12, 2002). "Toll-like receptor 4 polymorphisms and atherogenesis". The New England Journal of Medicine. 347 (24): 1978–1980, author reply 1978–1980. doi:10.1056/NEJM200212123472416. ISSN 1533-4406. PMID 12479194.
  140. ^ Beutler, E.; Gelbart, T.; Han, J. H.; Koziol, J. A.; Beutler, B. (January 1989). "Evolution of the genome and the genetic code: selection at the dinucleotide level by methylation and polyribonucleotide cleavage". Proceedings of the National Academy of Sciences of the United States of America. 86 (1): 192–196. Bibcode:1989PNAS...86..192B. doi:10.1073/pnas.86.1.192. ISSN 0027-8424. PMC 286430. PMID 2463621.
  141. ^ Truksa, Jaroslav; Gelbart, Terri; Peng, Hongfan; Beutler, Ernest; Beutler, Bruce; Lee, Pauline (November 2009). "Suppression of the hepcidin-encoding gene Hamp permits iron overload in mice lacking both hemojuvelin and matriptase-2/TMPRSS6". British Journal of Haematology. 147 (4): 571–581. doi:10.1111/j.1365-2141.2009.07873.x. ISSN 1365-2141. PMID 19751239. S2CID 205266224.
  142. ^ Du, Xin; She, Ellen; Gelbart, Terri; Truksa, Jaroslav; Lee, Pauline; Xia, Yu; Khovananth, Kevin; Mudd, Suzanne; Mann, Navjiwan; Moresco, Eva Marie Y.; Beutler, Ernest; Beutler, Bruce (May 23, 2008). "The serine protease TMPRSS6 is required to sense iron deficiency". Science. 320 (5879): 1088–1092. Bibcode:2008Sci...320.1088D. doi:10.1126/science.1157121. ISSN 1095-9203. PMC 2430097. PMID 18451267.
  143. ^ Wailoo, Keith. "Ernest Beutler QA - Hematology.org". Retrieved March 9, 2023.
  144. ^ Hildebrandt, Sabine; Kammertöns, Thomas; Lechner, Christian; Schmitt, Philipp; Schumann, Ralf R. (2019). "Dr. Käthe Beutler, 1896–1999". Medizinhistorisches Journal. 54 (4): 294–346. doi:10.25162/mhj-2019-0009. ISSN 0025-8431. S2CID 213008951.
  145. ^ "HANS G. BEUTLER, 46, PHYSICIST, IS DEAD; Research Aide on the Chicago U. Faculty Was Spectroscopist". The New York Times. December 19, 1942. Retrieved March 9, 2023.

External links Edit

 
Wikimedia Commons has media related to Bruce Beutler.
  • Official website
  •   Works on the topic Bruce Beutler at Wikisource

External links Edit

 
Wikimedia Commons has media related to Bruce Beutler.
  • Bruce A. Beutler on Nobelprize.org   including the Nobel lecture How Mammals Sense Infection: From Endotoxin to the Toll-like Receptors
  • Nobel Prize Inspiration Initiative
  • Scientific Publications – All publications of articles by Bruce A. Beutler listed in PubMed.
  • How we sense microbes: Genetic dissection of innate immunity in insects and mammals – Brief review of recent work, written with Jules A. Hoffmann.
  • Persistent Prospector - MD. Bruce Beutler by Ruth Williams
  • 2011 Video presentation by Dr. Bruce Beutler at University of Texas

October 21, 2023
bruce, beutler, this, biography, living, person, needs, additional, citations, verification, please, help, adding, reliable, sources, contentious, material, about, living, persons, that, unsourced, poorly, sourced, must, removed, immediately, from, article, ta. This biography of a living person needs additional citations for verification Please help by adding reliable sources Contentious material about living persons that is unsourced or poorly sourced must be removed immediately from the article and its talk page especially if potentially libelous Find sources Bruce Beutler news newspapers books scholar JSTOR July 2020 Learn how and when to remove this template message Bruce Alan Beutler ˈ b ɔɪ t l er BOYT ler born December 29 1957 is an American immunologist and geneticist Together with Jules A Hoffmann he received one half of the 2011 Nobel Prize in Physiology or Medicine for discoveries concerning the activation of innate immunity 1 Beutler discovered the long elusive receptor for lipopolysaccharide LPS also known as endotoxin He did so by identifying spontaneous mutations in the gene coding for mouse Toll like receptor 4 Tlr4 in two unrelated strains of LPS refractory mice and proving they were responsible for that phenotype 2 Subsequently and chiefly through the work of Shizuo Akira other TLRs were shown to detect signature molecules of most infectious microbes in each case triggering an innate immune response 3 4 5 6 7 Bruce BeutlerUniversity of Texas Southwestern Medical Center 2021Photograph by Brian CoatsBorn 1957 12 29 December 29 1957 age 65 Chicago IllinoisNationalityAmericanAlma materUniversity of Chicago University of California San DiegoSpouse s Barbara Lanzl c 1980 1988 divorced 3 children Awards2011 Nobel Prize in Physiology or MedicineScientific careerFieldsImmunologyInstitutionsUniversity of Texas Southwestern Medical CenterThe other half of the Nobel Prize went to Ralph M Steinman for his discovery of the dendritic cell and its role in adaptive immunity 1 Beutler is currently a Regental Professor and Director of the Center for the Genetics of Host Defense at the University of Texas Southwestern Medical Center in Dallas Texas 8 9 Contents 1 Early life and education 2 Scientific contributions 2 1 Isolation of tumor necrosis factor and discovery of its inflammation promoting effect 2 2 Invention of TNF inhibitors 2 3 Discovery of the LPS receptor and the role of TLRs in innate immune sensing 2 4 Random Germline Mutagenesis Forward Genetics in the mouse 2 5 Invention of Automated Meiotic Mapping 2 6 Developing drugs that activate TLRs 3 Awards and recognition 3 1 Awards 3 2 Honorary Doctoral Degrees 4 Family 5 See also 6 References 7 External links 8 External linksEarly life and education EditBorn in Chicago Illinois to a Jewish 10 family Beutler lived in Southern California between the ages of 2 and 18 1959 to 1977 For most of this time he lived in city of Arcadia a northeastern suburb of Los Angeles in the San Gabriel Valley During these years he spent much time hiking in the San Gabriel Mountains and in regional national parks Sequoia Yosemite Joshua Tree and Grand Canyon and was particularly fascinated by living things 11 These experiences impelled an intense interest in biological science His introduction to experimental biology acquired between the ages of 14 and 18 included work in the laboratory of his father Ernest Beutler then at the City of Hope Medical Center in Duarte CA There he learned to assay enzymes of red blood cells and became familiar with methods for protein isolation He published his studies of an electrophoretic variant of glutathione peroxidase 12 as well as the inherent catalytic activity of inorganic selenite 13 at the age of 17 Beutler also worked in the City of Hope laboratory of Susumu Ohno a geneticist known for his studies of evolution genome structure and sex differentiation in mammals Ohno hypothesized that the major histocompatibility complex proteins served as anchorage sites for organogenesis directing proteins 14 He further suggested that H Y antigen a minor histocompatibility protein encoded by a gene on the Y chromosome and absent in female mammals was responsible for directing organogenesis of the indifferent gonad to form a testis In studying H Y antigen 15 Beutler became conversant with immunology and mouse genetics during the 1970s While a college student at the University of California at San Diego Beutler worked in the laboratory of Dan Lindsley a Drosophila geneticist interested in spermatogenesis and spermiogenesis in the fruit fly There he learned to map phenotypes to chromosomal regions using visible phenotypic markers 11 He also worked in the laboratory of Abraham Braude an expert in the biology of LPS Beutler received his secondary school education at Polytechnic School in Pasadena California A precocious student he graduated from high school at the age of 16 enrolled in college at the University of California San Diego and graduated with a BA degree at the age of 18 in 1976 He then enrolled in medical school at the University of Chicago in 1977 and received his M D degree in 1981 at the age of 23 16 From 1981 to 1983 Beutler continued his medical training at the University of Texas Southwestern Medical Center in Dallas Texas as an intern in the Department of Internal Medicine and as a resident in the Department of Neurology However he found clinical medicine less interesting than laboratory science and decided to return to the laboratory Scientific contributions EditIsolation of tumor necrosis factor and discovery of its inflammation promoting effect Edit Beutler s focus on innate immunity began when he was a postdoctoral associate and later an assistant professor in the lab of Anthony Cerami at Rockefeller University 1983 1986 Drawing upon skills he had acquired earlier he isolated mouse cachectin from the conditioned medium of LPS activated mouse macrophages 17 Cachectin was hypothesized by Cerami to be a mediator of wasting in chronic disease Its biological activity the suppression of lipoprotein lipase synthesis in adipocytes was thought to contribute to wasting since lipoprotein lipase cleaves fatty acids from circulating triglycerides allowing their uptake and re esterification within fat cells 18 By sequential fractionation of LPS activated macrophage medium measuring cachectin activity at each step Beutler purified cachectin to homogeneity 19 Determining its N terminal sequence he recognized it as mouse tumor necrosis factor TNF and showed that it had strong TNF activity moreover that human TNF isolated by a very different assay had strong cachectin activity 18 Human TNF isolated contemporaneously by other workers 20 had to that time been defined only by its ability to kill cancer cells The discovery of a separate role for TNF as a catabolic switch was of considerable interest Of still greater importance Beutler demonstrated that TNF acted as a key mediator of endotoxin induced shock 21 This he accomplished by raising an antibody against mouse TNF which he used to neutralize TNF in living mice challenged with lipopolysaccharide LPS 21 The often lethal systemic inflammatory response to LPS was significantly mitigated by passive immunization against TNF The discovery that TNF caused an acute systemic inflammatory disease LPS induced shock presaged its causative role in numerous chronic inflammatory diseases With J M Dayer Beutler demonstrated that purified TNF could cause inflammation associated responses in cultured human synoviocytes secretion of collagenase and prostaglandin E2 22 This was an early hint that TNF might be causally important in rheumatoid arthritis as later shown by Feldmann Brennan and Maini 23 Beutler also demonstrated the existence of TNF receptors on most cell types 19 and correctly inferred the presence of two types of TNF receptor distinguished by their affinities later cloned and designated p55 and p75 TNF receptors to denote their approximate molecular weights 24 25 26 27 28 Before a sensitive immunoassay for TNF was feasible Beutler used these receptors in a binding competition assay using radio iodinated TNF as a tracer which allowed him to precisely measure TNF in biological fluids 29 Invention of TNF inhibitors Edit Beutler was recruited to a faculty position at UT Southwestern Medical Center and the Howard Hughes Medical Institute in 1986 Aware that TNF blockade might have clinical applications he along with a graduate student David Crawford and a postdoctoral associate Karsten Peppel invented and patented recombinant molecules expressly designed to neutralize TNF in vivo Patent No US5447851B1 30 Fusing the binding portion of TNF receptor proteins to the heavy chain of an immunoglobulin molecule to force receptor dimerization 30 they produced chimeric reagents with surprisingly high affinity and specificity for both TNF and a closely related cytokine called lymphotoxin low antigenicity and excellent stability in vivo The human p75 receptor chimeric protein was later used extensively as the drug Etanercept in the treatment of rheumatoid arthritis Crohn s disease psoriasis and other forms of inflammation Marketed by Amgen Etanercept achieved more than 74B in sales 31 Discovery of the LPS receptor and the role of TLRs in innate immune sensing Edit From the mid 1980s onward Beutler was interested in the mechanism by which LPS activates mammalian immune cells chiefly macrophages 18 21 but dendritic cells and B cells as well sometimes leading to uncontrollable Gram negative septic shock 32 33 34 but also promoting the well known adjuvant effect of LPS 35 and B cell mitogenesis 36 37 and antibody production A single highly specific LPS receptor was presumed to exist as early as the 1960s based on the fact that allelic mutations in two separate strains of mice affecting a discrete genetic locus on chromosome 4 termed Lps abolished LPS sensing 36 38 Although this receptor had been widely pursued it remained elusive Beutler reasoned that in finding the LPS receptor insight might be gained into the first molecular events that transpire upon an encounter between the host and microbial invaders 39 Utilizing positional cloning in an effort that began in 1993 and lasted five years Beutler together with several postdoctoral associates including Alexander Poltorak measured TNF production as a qualitative phenotypic endpoint of the LPS response Analyzing more than 2 000 meioses they confined the LPS receptor encoding gene to a region of the genome encompassing approximately 5 8 million base pairs of DNA 2 Sequencing most of the interval they identified a gene within which each of two LPS refractory strains of mice C3H HeJ and C57BL 10ScCr had deleterious mutations The gene Tlr4 encoded a cell surface protein with cytoplasmic domain homology to the interleukin 1 receptor and several other homologous genes that were scattered across the mouse genome Beutler and his team thus proved that one of the mammalian Toll like receptors TLR4 acts as the membrane spanning component of the mammalian LPS receptor complex 2 40 41 They also showed that while mouse TLR4 is activated by a tetra acylated LPS like molecule lipid IVa human TLR4 is not recapitulating the species specificity for LPS partial structures 41 It was deduced that direct contact between TLR4 and LPS is a prerequisite for cell activation 41 Later an extracellular component of the LPS receptor complex MD 2 also known as lymphocyte antigen 96 was identified by R Shimazu and colleagues 42 The structure of the complex with and without LPS bound was solved by Jie Oh Lee and colleagues in 2009 43 Jules Hoffmann and colleagues had earlier shown that the Drosophila Toll protein originally known for its role in embryogenesis was essential for the antimicrobial peptide response to fungal infection 44 However no molecule derived from fungi actually became bound to Toll rather a proteolytic cascade led to the activation of an endogenous ligand the protein Spatzle This activated NF kB within cells of the fat body leading to antimicrobial peptide secretion Aware of this work Charles Janeway and Ruslan Medzhitov overexpressed a modified version of human TLR4 which they called h Toll and found it capable of activating the transcription factor NF kB in mammalian cells 45 They speculated that TLR4 was a pattern recognition receptor However they provided no evidence that TLR4 recognized any molecule of microbial origin If a ligand did exist it might have been endogenous as in the fruit fly where Toll recognizes the endogenous protein Spatzle or as in the case of the IL 1 receptor which recognizes the endogenous cytokine IL 1 Indeed numerous cell surface receptors including the TGFb receptor B cell receptor and T cell receptor activate NF kB In short it was not clear what TLR4 recognized nor what its function was Separate publications also based on transfection overexpression studies held that TLR2 rather than TLR4 was the LPS receptor 46 47 The genetic evidence of Beutler and coworkers correctly identified TLR4 as the specific and non redundant cell surface receptor for LPS fully required for virtually all LPS activities This suggested that other TLRs of which ten are now known to exist in humans might also act as sensors of infection in mammals 48 each detecting other signature molecules made by microbes whether or not they were pathogens in the classical sense of the term The other TLRs like TLR4 do indeed initiate innate immune responses By promoting inflammatory signaling TLRs can also mediate pathologic effects including fever systemic inflammation and shock Sterile inflammatory and autoimmune diseases such as systemic lupus erythematosus also elicit TLR signaling and disruption of signaling from the nucleic acid sensing TLRs can favorably modify the disease phenotype 49 50 51 52 53 54 55 56 Random Germline Mutagenesis Forward Genetics in the mouse Edit After completing the positional cloning of the Lps locus in 1998 Beutler continued to apply a forward genetic approach to the analysis of immunity in mammals In this process germline mutations that alter immune function are created in mice through a random process using the alkylating agent ENU detected by their phenotypic effects and then isolated by positional cloning 57 This work disclosed numerous essential signaling molecules required for the innate immune response 58 59 60 61 62 63 64 and helped to delineate the biochemistry of innate immunity Among the genes detected was Ticam1 implicated by an ENU induced phenotype called Lps2 58 The encoded protein TICAM1 also known as TRIF was a new adaptor molecule binding to the cytoplasmic domains of both TLR3 and TLR4 and needed for signaling by each Another phenotype called 3d to connote a triple defect in TLR signaling affected a gene of unknown function called Unc93b1 60 TLRs 3 7 and 9 nucleic acid sensing TLRs failed to signal in homozygotes for the mutation These TLRs were found to be endosomal and physically interact with the UNC93B1 protein which transports them to the endosomal compartment 65 Humans with mutations in UNC93B1 the human ortholog of the same gene were subsequently found to be susceptible to recurrent Herpes simplex virus HSV encephalitis in which reactivation of latent virus occurs repeatedly in the trigeminal ganglion at the base of the midbrain leading to cortical neuron death 66 Yet another protein needed to make the endosomal environment suitable for TLR signaling was SLC15A4 identified based on the phenotype feeble 67 feeble was identified in a screen in which immunostimulatory DNA was administered to mice intravenously with measurement of the systemic type I interferon response Failure of this response which is dependent on TLR9 signaling from plasmacytoid dendritic cells pDC was observed in homozygous mutants and subsequently failure of TLR7 but not TLR3 signaling was observed as well Because the feeble mutation suppressed SLE in mice 52 the SLC15A4 protein has become a target of interest for drug development 68 In all Beutler and colleagues detected 77 mutations in 36 genes in which ENU induced mutations created defects of TLR signaling detected due to faulty TNF and or interferon responses These genes encoded all TLRs kept under surveillance in screening all of the four adapter proteins that signal from TLRs kinases and other signaling proteins downstream chaperones needed to escort TLRs to their destinations proteins that promote the availability of TLR ligands proteins involved in vesicle transport and proteins involved in transcriptional responses to TLR signaling or the post translational processing of TNF and or type I interferons the proteins assayed in screening Beutler and colleagues also used ENU mutagenesis to study the global response to a defined infectious agent They measured susceptibility to mouse cytomegalovirus MCMV and identified numerous genes that make a life or death difference during infection terming this set of genes the MCMV resistome 69 70 These genes were grouped into sensing signaling effector homeostatic and developmental categories some of which were wholly unexpected In the homeostatic category for example Kir6 1 ATP sensitive potassium channels in the smooth muscle of the coronary arteries serve an essential role in the maintenance of blood flow during MCMV infection and mutations that damage these channels cause sudden death during infection 71 Other genetic screens in the Beutler laboratory were used to identify genes that mediate homeostatic adaptations of the intestinal epithelium following a cytotoxic insult 72 73 74 75 76 77 78 prevent allergic responses 79 diabetes 80 81 or obesity 82 83 84 support normal hematopoiesis 85 86 87 88 89 90 91 92 93 94 and enable humoral and cellular immunity 95 96 97 98 Some of these beginning 2015 were identified by a new process called automated meiotic mapping which enabled greatly accelerated mutation identification compared to traditional genetic mapping see below In the course of their work Beutler and his colleagues also discovered genes required for biological processes such as normal iron absorption 99 hearing 100 pigmentation 101 102 metabolism 82 84 103 104 105 and embryonic development 106 Many human diseases were ultimately linked to variants in the corresponding human genes after initial identification in the mouse by the Beutler laboratory 66 107 108 109 or by the laboratories of collaborating investigators 110 111 112 Invention of Automated Meiotic Mapping Edit Prior to 2013 despite the development of methods for massively parallel sequencing and their application in finding induced germline mutations 113 114 115 positional cloning remained a slow process limited by the need to genetically map mutations to chromosomal intervals to ascertain which induced mutation among the average of approximately 60 changes in coding and splicing function induced per pedigree was responsible for an observed phenotype This required expansion of a mutant stock outcrossing to a mapping strain backcrossing and genotypic and phenotypic analysis of F2 offspring Moreover when phenotypic screening was performed prior to positional cloning only large effect size mutations producing essentially qualitative phenotypes were recoverable Beutler invented a means of instantly identifying ENU induced mutations that cause phenotypes 116 The process called automated meiotic mapping AMM eliminates the need to breed mutant mice to a mapping strain as required in classical genetic mapping and flags causative mutations as soon as phenotypic assay data are collected In a laboratory setting it accelerates positional cloning approximately 200 fold and permits ongoing measurement of genome saturation as mutagenesis progresses 117 Not only qualitative phenotypes but subtle quantitative phenotypes are detectable and mapped to individual mutations hence the sensitivity of forward genetics is dramatically increased AMM depends on statistical computation to detect associations between mutations in either the homozygous or heterozygous state and deviant phenotypes 116 In addition machine learning software trained on the outcome of many thousands of experiments in which putative causative mutations were re created and re assayed for phenotype is used to assess data quality 118 As of 2022 more than 260 000 ENU induced non synonymous coding or splice site mutations had been assayed for phenotypic effects and more than 5 800 mutations in approximately 2 500 genes had been declared causative of phenotype s For certain screens such as flow cytometry performed on the blood of germline mutant mice more than 55 saturation of the genome has been achieved i e more than 55 of all genes in which mutations will create flow cytometric aberrations in the peripheral blood have been detected most of them based on assessment of multiple alleles as of July 2021 118 AMM led to the discovery of many new immunodeficiency disorders 88 89 90 91 92 93 94 85 98 and disorders of bone morphology or mineral density 111 112 vision 119 and metabolism 82 84 104 105 Of note AMM was used in the identification of a chemosensor that mediates innate fear behavior in mice and an autism gene found first in mice and then shown to cause autism in humans 110 120 AMM has also permitted high speed searches for mutations that suppress or augment disease phenotypes for example the development of autoimmune Type 1 diabetes in mice of the NOD strain 80 81 It offers a rational way to investigate the pathogenesis of complex disease phenotypes in general in which many loci invariably contribute to susceptibility or resistance to disease and disease occurs in those individuals with an unfavorable imbalance between these opposing influences Developing drugs that activate TLRs Edit Beutler has collaborated with Dale L Boger and his research group to identify synthetic small molecule agonists of mammalian TLRs which may be used in combination with defined molecular antigens to precisely target and coordinate innate and adaptive immune responses Neoseptins small molecules with no relationship to the structure of LPS were shown to bind to the TLR4 MD2 complex in such a manner that two drug molecules trigger a conformational change similar to that elicited by an authentic LPS molecule Diprovocims which bear no structural similarity to bacterial lipopeptides activate the TLR1 TLR2 heterodimer complex that normally acts as a receptor for tri acylated lipopeptide molecules These studies demonstrated that TLR2 and TLR4 can indeed respond to molecules other than classical microbial ligands and set a new standard for verifying such interactions in that X ray crystallography was used to demonstrate the binding of neoseptins and diprovocims to their respective TLR targets at atomic level resolution Beutler and colleagues also showed again using X ray crystallography combined with biological assays that endogenous sulfatides are capable of binding to the TLR4 MD2 complex causing its activation 121 122 123 124 125 126 127 Awards and recognition EditThis section of a biography of a living person needs additional citations for verification Please help by adding reliable sources Contentious material about living persons that is unsourced or poorly sourced must be removed immediately from the article and its talk page especially if potentially libelous Find sources Bruce Beutler news newspapers books scholar JSTOR August 2023 Learn how and when to remove this template message nbsp Jules A Hoffmann Goran K Hansson chairman of the Nobel Committee for Physiology or Medicine and Beutler nbsp Jules A Hoffmann background and Beutler nbsp Bruce Beutler at the Nobel Prize press conference at Karolinska SolnaAwards Edit 1993 Alexander von Humboldt Fellow Germany 1994 Young Investigator Award American Federation for Clinical Research United States 2001 Highly Cited Researcher Institute for Scientific Information United States 2004 Robert Koch Prize Robert Koch Stiftung Germany shared with Jules A Hoffmann and Shizuo Akira 2006 William B Coley Award Cancer Research Institute United States shared with Shizuo Akira 2006 Gran Prix Charles Leopold Mayer Academie des Sciences France 2007 Recipient of NIH NIGMS MERIT Award United States 2007 Balzan Prize International Balzan Foundation Italy and Switzerland shared with Jules A Hoffmann 2008 Frederik B Bang Award The Stanley Watson Foundation United States 2008 Citation Laureate Thomson Reuters 2009 Will Rogers Institute Annual Prize for Scientific Research United States 2009 Albany Medical Center Prize in Medicine and Biomedical Research United States shared with Charles A Dinarello and Ralph M Steinman 128 2010 University of Chicago Professional Achievement Citation United States 2011 Shaw Prize China shared with Jules A Hoffmann and Ruslan M Medzhitov 2011 Nobel Prize in Physiology or Medicine Sweden shared with Jules A Hoffmann and Ralph M Steinman 1 2012 Drexel Medicine Prize in Immunology United States 2013 Rabbi Shai Shacknai Memorial Prize in Immunology and Cancer Research The Hebrew University of Jerusalem Israel 2013 Distinguished Service Award University of Chicago United States 2013 Korsmeyer Award United States 2016 UCSD Distinguished Alumnus Award United StatesHonorary Doctoral Degrees Edit 2007 Doctor Med Honoris Causa Technical University of Munich Germany 2009 Honorary Doctoral Degree Xiamen University China 2012 Honorary Professor Trinity College Ireland 2013 Honorary Professor Peking University China 2014 Honorary Professor Shanghai Jiao Tong University China 2014 Chair of the Beutler Institute Council Xiamen University China 2014 Honorary Professor Xiamen University China 2015 Doctor Honoris Causa University of Chile Chile 2015 Doctor Honoris Causa University of Marseille France 2015 Doctor Honoris Causa University of Brasilia Brazil 2015 Doctor Honoris Causa 129 Norwegian University of Science and Technology NTNU Norway 2015 Honorary Professor at Naresuan University Thailand 2016 Honorary Doctorate University of Athens Greece 2017 Doctor Med Honoris Causa University of Ottawa Canada 2017 Honorary Professor Tianjin University China 2019 Honorary Degree Jewish Theological Seminary United States 2019 Laurea Magistrale honoris causa in Medicina e Chirurgia LM41 130 Universita Magna Grecia of Catanzaro ItalyFamily EditBruce Beutler was the third son of Ernest Beutler 1928 2008 and Brondelle May Beutler nee Fleisher 1928 2019 His siblings included two older brothers Steven b 1952 and Earl b 1954 and a younger sister Deborah b 1962 citation needed Ernest Beutler was a hematologist and medical geneticist famed for his studies of G 6 PD deficiency 131 other hemolytic anemias 132 133 iron metabolism 134 glycolipid storage diseases 135 and leukemias 136 137 as well as his discovery of X chromosome inactivation 138 He was a Professor and department chairman at The Scripps Research Institute contemporaneously with Bruce The two collaborated productively on several topics prior to Ernest Beutler s death in 2008 12 13 139 140 141 142 Both of Ernest Beutler s parents were physicians 143 Bruce Beutler s paternal grandmother Kathe Beutler nee Italiener daughter of Anna Rothstein 1896 1999 144 was a pediatrician trained at the Charite hospital in Berlin earning her medical diploma in 1923 Kathe Italiener married Alfred Beutler in 1925 Also a physician Alfred Beutler was a cousin to the spectral physicist Hans G Beutler 1896 1942 who worked at the Kaiser Wilhelm Institute and the University of Berlin before emigrating to the USA in 1936 He continued his work at the University of Chicago until his death 145 Bruce Beutler married Barbara Beutler nee Lanzl in 1980 and divorced in 1988 Three sons were born to the couple citation needed See also EditList of Jewish Nobel laureatesReferences Edit a b c Nobel Prize in Physiology or Medicine 2011 Press release Nobel Foundation October 3 2011 a b c Poltorak A He X Smirnova I Liu M Y Van Huffel C Du X Birdwell D Alejos E Silva M Galanos C Freudenberg M Ricciardi Castagnoli P Layton B Beutler B December 11 1998 Defective LPS signaling in C3H HeJ and C57BL 10ScCr mice mutations in Tlr4 gene Science 282 5396 2085 2088 doi 10 1126 science 282 5396 2085 ISSN 0036 8075 PMID 9851930 Hemmi Hiroaki Kaisho Tsuneyasu Takeuchi Osamu Sato Shintaro Sanjo Hideki Hoshino Katsuaki Horiuchi Takao Tomizawa Hideyuki Takeda Kiyoshi Akira Shizuo January 22 2002 Small anti viral compounds activate immune cells via the TLR7 MyD88 dependent signaling pathway Nature Immunology 3 2 196 200 doi 10 1038 ni758 ISSN 1529 2908 PMID 11812998 S2CID 1694900 Hemmi H Takeuchi O Kawai T Kaisho T Sato S Sanjo H Matsumoto M Hoshino K Wagner H Takeda K Akira S December 7 2000 A Toll like receptor recognizes bacterial DNA Nature 408 6813 740 745 Bibcode 2000Natur 408 740H doi 10 1038 35047123 ISSN 0028 0836 PMID 11130078 S2CID 4405163 Takeuchi O Hoshino K Kawai T Sanjo H Takada H Ogawa T Takeda K Akira S October 1 1999 Differential roles of TLR2 and TLR4 in recognition of gram negative and gram positive bacterial cell wall components Immunity 11 4 443 451 doi 10 1016 s1074 7613 00 80119 3 ISSN 1074 7613 PMID 10549626 Takeuchi O Kawai T Muhlradt P F Morr M Radolf J D Zychlinsky A Takeda K Akira S July 1 2001 Discrimination of bacterial lipoproteins by Toll like receptor 6 International Immunology 13 7 933 940 doi 10 1093 intimm 13 7 933 ISSN 0953 8178 PMID 11431423 Takeuchi Osamu Sato Shintaro Horiuchi Takao Hoshino Katsuaki Takeda Kiyoshi Dong Zhongyun Modlin Robert L Akira Shizuo July 1 2002 Cutting edge role of Toll like receptor 1 in mediating immune response to microbial lipoproteins Journal of Immunology 169 1 10 14 doi 10 4049 jimmunol 169 1 10 ISSN 0022 1767 PMID 12077222 S2CID 22686400 Ravindran S 2013 Profile of Bruce A Beutler Proceedings of the National Academy of Sciences 110 32 12857 8 Bibcode 2013PNAS 11012857R doi 10 1073 pnas 1311624110 PMC 3740904 PMID 23858464 Center for the Genetics of Host Defense UT Southwestern Dallas TX Retrieved March 9 2023 Jewish Nobel Prize laureates Physiology and medicine www science co il Retrieved March 29 2023 a b Bruce A Beutler Biographical NobelPrize org Retrieved March 9 2023 a b Beutler E West C Beutler B October 1974 Electrophoretic polymorphism of glutathione peroxidase Annals of Human Genetics 38 2 163 169 doi 10 1111 j 1469 1809 1974 tb01947 x ISSN 0003 4800 PMID 4467780 S2CID 32294741 a b Beutler E Beutler B Matsumoto J July 15 1975 Glutathione peroxidase activity of inorganic selenium and seleno DL cysteine Experientia 31 7 769 770 doi 10 1007 BF01938453 ISSN 0014 4754 PMID 1140308 S2CID 26234261 Ohno S January 1977 The original function of MHC antigens as the general plasma membrane anchorage site of organogenesis directing proteins Immunological Reviews 33 59 69 doi 10 1111 j 1600 065X 1977 tb00362 x ISSN 0105 2896 PMID 66186 S2CID 45992817 Beutler B Nagai Y Ohno S Klein G Shapiro I M March 1978 The HLA dependent expression of testis organizing H Y antigen by human male cells Cell 13 3 509 513 doi 10 1016 0092 8674 78 90324 0 ISSN 0092 8674 PMID 77737 S2CID 33827976 Easton John October 10 2011 Alumnus Bruce Beutler MD 81 to receive 2011 Nobel Prize in Medicine uchicago news Retrieved March 9 2023 Bruce Beutler MD The American Society for Clinical Investigation Retrieved October 18 2023 a b c Beutler B Greenwald D Hulmes J D Chang M Pan Y C Mathison J Ulevitch R Cerami A August 1 1985 Identity of tumour necrosis factor and the macrophage secreted factor cachectin Nature 316 6028 552 554 Bibcode 1985Natur 316 552B doi 10 1038 316552a0 ISSN 0028 0836 PMID 2993897 S2CID 4339006 a b Beutler B Mahoney J Le Trang N Pekala P Cerami A May 1 1985 Purification of cachectin a lipoprotein lipase suppressing hormone secreted by endotoxin induced RAW 264 7 cells The Journal of Experimental Medicine 161 5 984 995 doi 10 1084 jem 161 5 984 ISSN 0022 1007 PMC 2187615 PMID 3872925 Aggarwal B B Kohr W J Hass P E Moffat B Spencer S A Henzel W J Bringman T S Nedwin G E Goeddel D V Harkins R N February 25 1985 Human tumor necrosis factor Production purification and characterization The Journal of Biological Chemistry 260 4 2345 2354 doi 10 1016 S0021 9258 18 89560 6 ISSN 0021 9258 PMID 3871770 a b c Beutler B Milsark I W Cerami A C August 30 1985 Passive immunization against cachectin tumor necrosis factor protects mice from lethal effect of endotoxin Science 229 4716 869 871 Bibcode 1985Sci 229 869B doi 10 1126 science 3895437 ISSN 0036 8075 PMID 3895437 Dayer J M Beutler B Cerami A December 1 1985 Cachectin tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts The Journal of Experimental Medicine 162 6 2163 2168 doi 10 1084 jem 162 6 2163 ISSN 0022 1007 PMC 2187983 PMID 2999289 Feldmann M Brennan F M Maini R N 1996 Role of cytokines in rheumatoid arthritis Annual Review of Immunology 14 397 440 doi 10 1146 annurev immunol 14 1 397 ISSN 0732 0582 PMID 8717520 Engelmann H Novick D Wallach D January 25 1990 Two tumor necrosis factor binding proteins purified from human urine Evidence for immunological cross reactivity with cell surface tumor necrosis factor receptors The Journal of Biological Chemistry 265 3 1531 1536 doi 10 1016 S0021 9258 19 40049 5 ISSN 0021 9258 PMID 2153136 Loetscher H Pan Y C Lahm H W Gentz R Brockhaus M Tabuchi H Lesslauer W April 20 1990 Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor Cell 61 2 351 359 doi 10 1016 0092 8674 90 90815 v ISSN 0092 8674 PMID 2158862 S2CID 42245440 Nophar Y Kemper O Brakebusch C Englemann H Zwang R Aderka D Holtmann H Wallach D October 1 1990 Soluble forms of tumor necrosis factor receptors TNF Rs The cDNA for the type I TNF R cloned using amino acid sequence data of its soluble form encodes both the cell surface and a soluble form of the receptor The EMBO Journal 9 10 3269 3278 doi 10 1002 j 1460 2075 1990 tb07526 x ISSN 0261 4189 PMC 552060 PMID 1698610 Schall T J Lewis M Koller K J Lee A Rice G C Wong G H Gatanaga T Granger G A Lentz R Raab H April 20 1990 Molecular cloning and expression of a receptor for human tumor necrosis factor Cell 61 2 361 370 doi 10 1016 0092 8674 90 90816 w ISSN 0092 8674 PMID 2158863 S2CID 36187863 Smith C A Davis T Anderson D Solam L Beckmann M P Jerzy R Dower S K Cosman D Goodwin R G May 25 1990 A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins Science 248 4958 1019 1023 Bibcode 1990Sci 248 1019S doi 10 1126 science 2160731 ISSN 0036 8075 PMID 2160731 Poltorak A Peppel K Beutler B February 28 1994 Receptor mediated label transfer assay RELAY a novel method for the detection of plasma tumor necrosis factor at attomolar concentrations Journal of Immunological Methods 169 1 93 99 doi 10 1016 0022 1759 94 90128 7 ISSN 0022 1759 PMID 8133076 a b Peppel K Crawford D Beutler B December 1 1991 A tumor necrosis factor TNF receptor IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity The Journal of Experimental Medicine 174 6 1483 1489 doi 10 1084 jem 174 6 1483 ISSN 0022 1007 PMC 2119031 PMID 1660525 Gardner Jonathan November 1 2021 A three decade monopoly how Amgen built a patent thicket around its top selling drug BioPharma Dive BioPharma Dive Retrieved March 9 2023 Beutler B Poltorak A July 2001 Sepsis and evolution of the innate immune response Critical Care Medicine 29 7 Suppl S2 6 discussion S6 7 doi 10 1097 00003246 200107001 00002 ISSN 0090 3493 PMID 11445725 Beutler Bruce 1988 Orchestration of septic shock by cytokines the role of cachectin tumor necrosis factor In Roth B ed Molecular and Cellular Mechanisms of Septic Shock New York Alan R Liss Inc pp 219 235 Beutler B 1992 Cytokines in Shock 1992 In Lamy M Thijs LG eds Mediators of Sepsis Heidelberg Springer Berlin pp 51 67 Johnson A G Gaines S Landy M February 1 1956 Studies on the O antigen of Salmonella typhosa V Enhancement of antibody response to protein antigens by the purified lipopolysaccharide The Journal of Experimental Medicine 103 2 225 246 doi 10 1084 jem 103 2 225 ISSN 0022 1007 PMC 2136584 PMID 13286429 a b Coutinho A Meo T December 1978 Genetic basis for unresponsiveness to lipopolysaccharide in C57BL 10Cr mice Immunogenetics 7 1 17 24 doi 10 1007 BF01843983 ISSN 0093 7711 PMID 21302052 S2CID 29425605 Watson J Riblet R November 1 1974 Genetic control of responses to bacterial lipopolysaccharides in mice I Evidence for a single gene that influences mitogenic and immunogenic respones sic to lipopolysaccharides The Journal of Experimental Medicine 140 5 1147 1161 doi 10 1084 jem 140 5 1147 ISSN 0022 1007 PMC 2139714 PMID 4138849 Sultzer B M September 21 1968 Genetic control of leucocyte responses to endotoxin Nature 219 5160 1253 1254 Bibcode 1968Natur 219 1253S doi 10 1038 2191253a0 ISSN 0028 0836 PMID 4877918 S2CID 41633552 Beutler Bruce January 2002 Toll like receptors how they work and what they do Current Opinion in Hematology 9 1 2 10 doi 10 1097 00062752 200201000 00002 ISSN 1065 6251 PMID 11753071 S2CID 36843541 Du X Poltorak A Silva M Beutler B 1999 Analysis of Tlr4 mediated LPS signal transduction in macrophages by mutational modification of the receptor Blood Cells Molecules amp Diseases 25 5 6 328 338 doi 10 1006 bcmd 1999 0262 ISSN 1079 9796 PMID 10660480 a b c Poltorak A Ricciardi Castagnoli P Citterio S Beutler B February 29 2000 Physical contact between lipopolysaccharide and toll like receptor 4 revealed by genetic complementation Proceedings of the National Academy of Sciences of the United States of America 97 5 2163 2167 Bibcode 2000PNAS 97 2163P doi 10 1073 pnas 040565397 ISSN 0027 8424 PMC 15771 PMID 10681462 Shimazu R Akashi S Ogata H Nagai Y Fukudome K Miyake K Kimoto M June 7 1999 MD 2 a molecule that confers lipopolysaccharide responsiveness on Toll like receptor 4 The Journal of Experimental Medicine 189 11 1777 1782 doi 10 1084 jem 189 11 1777 ISSN 0022 1007 PMC 2193086 PMID 10359581 Park Beom Seok Song Dong Hyun Kim Ho Min Choi Byong Seok Lee Hayyoung Lee Jie Oh April 30 2009 The structural basis of lipopolysaccharide recognition by the TLR4 MD 2 complex Nature 458 7242 1191 1195 Bibcode 2009Natur 458 1191P doi 10 1038 nature07830 ISSN 1476 4687 PMID 19252480 S2CID 4396446 Lemaitre B Nicolas E Michaut L Reichhart J M Hoffmann J A September 20 1996 The dorsoventral regulatory gene cassette spatzle Toll cactus controls the potent antifungal response in Drosophila adults Cell 86 6 973 983 doi 10 1016 s0092 8674 00 80172 5 ISSN 0092 8674 PMID 8808632 S2CID 10736743 Medzhitov R Preston Hurlburt P Janeway C A July 24 1997 A human homologue of the Drosophila Toll protein signals activation of adaptive immunity Nature 388 6640 394 397 doi 10 1038 41131 ISSN 0028 0836 PMID 9237759 S2CID 4311321 Kirschning C J Wesche H Merrill Ayres T Rothe M December 7 1998 Human toll like receptor 2 confers responsiveness to bacterial lipopolysaccharide The Journal of Experimental Medicine 188 11 2091 2097 doi 10 1084 jem 188 11 2091 ISSN 0022 1007 PMC 2212382 PMID 9841923 Yang R B Mark M R Gray A Huang A Xie M H Zhang M Goddard A Wood W I Gurney A L Godowski P J September 17 1998 Toll like receptor 2 mediates lipopolysaccharide induced cellular signalling Nature 395 6699 284 288 Bibcode 1998Natur 395 284Y doi 10 1038 26239 ISSN 0028 0836 PMID 9751057 S2CID 4422827 Beutler B Poltorak A June 2000 Positional cloning of Lps and the general role of toll like receptors in the innate immune response European Cytokine Network 11 2 143 152 ISSN 1148 5493 PMID 10903793 Christensen Sean R Shupe Jonathan Nickerson Kevin Kashgarian Michael Flavell Richard A Shlomchik Mark J September 2006 Toll like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus Immunity 25 3 417 428 doi 10 1016 j immuni 2006 07 013 ISSN 1074 7613 PMID 16973389 Brown Grant J Canete Pablo F Wang Hao Medhavy Arti Bones Josiah Roco Jonathan A He Yuke Qin Yuting Cappello Jean Ellyard Julia I Bassett Katharine Shen Qian Burgio Gaetan Zhang Yaoyuan Turnbull Cynthia May 2022 TLR7 gain of function genetic variation causes human lupus Nature 605 7909 349 356 Bibcode 2022Natur 605 349B doi 10 1038 s41586 022 04642 z ISSN 1476 4687 PMC 9095492 PMID 35477763 Leibler Claire John Shinu Elsner Rebecca A Thomas Kayla B Smita Shuchi Joachim Stephen Levack Russell C Callahan Derrick J Gordon Rachael A Bastacky Sheldon Fukui Ryutaro Miyake Kensuke Gingras Sebastien Nickerson Kevin M Shlomchik Mark J October 2022 Genetic dissection of TLR9 reveals complex regulatory and cryptic proinflammatory roles in mouse lupus Nature Immunology 23 10 1457 1469 doi 10 1038 s41590 022 01310 2 ISSN 1529 2916 PMC 9561083 PMID 36151396 a b Baccala Roberto Gonzalez Quintial Rosana Blasius Amanda L Rimann Ivo Ozato Keiko Kono Dwight H Beutler Bruce Theofilopoulos Argyrios N February 19 2013 Essential requirement for IRF8 and SLC15A4 implicates plasmacytoid dendritic cells in the pathogenesis of lupus Proceedings of the National Academy of Sciences of the United States of America 110 8 2940 2945 Bibcode 2013PNAS 110 2940B doi 10 1073 pnas 1222798110 ISSN 1091 6490 PMC 3581947 PMID 23382217 Kono Dwight H Haraldsson M Katarina Lawson Brian R Pollard K Michael Koh Yi Ting Du Xin Arnold Carrie N Baccala Roberto Silverman Gregg J Beutler Bruce A Theofilopoulos Argyrios N July 21 2009 Endosomal TLR signaling is required for anti nucleic acid and rheumatoid factor autoantibodies in lupus Proceedings of the National Academy of Sciences of the United States of America 106 29 12061 12066 Bibcode 2009PNAS 10612061K doi 10 1073 pnas 0905441106 ISSN 1091 6490 PMC 2715524 PMID 19574451 Lau Christina M Broughton Courtney Tabor Abigail S Akira Shizuo Flavell Richard A Mamula Mark J Christensen Sean R Shlomchik Mark J Viglianti Gregory A Rifkin Ian R Marshak Rothstein Ann November 7 2005 RNA associated autoantigens activate B cells by combined B cell antigen receptor Toll like receptor 7 engagement The Journal of Experimental Medicine 202 9 1171 1177 doi 10 1084 jem 20050630 ISSN 0022 1007 PMC 2213226 PMID 16260486 Leadbetter Elizabeth A Rifkin Ian R Hohlbaum Andreas M Beaudette Britte C Shlomchik Mark J Marshak Rothstein Ann April 11 2002 Chromatin IgG complexes activate B cells by dual engagement of IgM and Toll like receptors Nature 416 6881 603 607 doi 10 1038 416603a ISSN 0028 0836 PMID 11948342 S2CID 4370544 Viglianti Gregory A Lau Christina M Hanley Timothy M Miko Benjamin A Shlomchik Mark J Marshak Rothstein Ann December 2003 Activation of autoreactive B cells by CpG dsDNA Immunity 19 6 837 847 doi 10 1016 s1074 7613 03 00323 6 ISSN 1074 7613 PMID 14670301 Beutler Bruce Du Xin Xia Yu July 2007 Precis on forward genetics in mice Nature Immunology 8 7 659 664 doi 10 1038 ni0707 659 ISSN 1529 2908 PMID 17579639 S2CID 28309476 a b Hoebe K Du X Georgel P Janssen E Tabeta K Kim S O Goode J Lin P Mann N Mudd S Crozat K Sovath S Han J Beutler B August 14 2003 Identification of Lps2 as a key transducer of MyD88 independent TIR signalling Nature 424 6950 743 748 Bibcode 2003Natur 424 743H doi 10 1038 nature01889 ISSN 1476 4687 PMID 12872135 S2CID 15608748 Hoebe Kasper Georgel Philippe Rutschmann Sophie Du Xin Mudd Suzanne Crozat Karine Sovath Sosathya Shamel Louis Hartung Thomas Zahringer Ulrich Beutler Bruce February 3 2005 CD36 is a sensor of diacylglycerides Nature 433 7025 523 527 Bibcode 2005Natur 433 523H doi 10 1038 nature03253 ISSN 1476 4687 PMID 15690042 S2CID 4406318 a b Tabeta Koichi Hoebe Kasper Janssen Edith M Du Xin Georgel Philippe Crozat Karine Mudd Suzanne Mann Navjiwan Sovath Sosathya Goode Jason Shamel Louis Herskovits Anat A Portnoy Daniel A Cooke Michael Tarantino Lisa M January 15 2006 The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll like receptors 3 7 and 9 Nature Immunology 7 2 156 164 doi 10 1038 ni1297 ISSN 1529 2908 PMID 16415873 S2CID 33401155 Croker Ben A Lawson Brian R Rutschmann Sophie Berger Michael Eidenschenk Celine Blasius Amanda L Moresco Eva Marie Y Sovath Sosathya Cengia Louise Shultz Leonard D Theofilopoulos Argyrios N Pettersson Sven Beutler Bruce Alan September 30 2008 Inflammation and autoimmunity caused by a SHP1 mutation depend on IL 1 MyD88 and a microbial trigger Proceedings of the National Academy of Sciences of the United States of America 105 39 15028 15033 Bibcode 2008PNAS 10515028C doi 10 1073 pnas 0806619105 ISSN 1091 6490 PMC 2567487 PMID 18806225 Shi Hexin Wang Ying Li Xiaohong Zhan Xiaoming Tang Miao Fina Maggy Su Lijing Pratt David Bu Chun Hui Hildebrand Sara Lyon Stephen Scott Lindsay Quan Jiexia Sun Qihua Russell Jamie December 7 2015 NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7 a new inflammasome component Nature Immunology 17 3 250 258 doi 10 1038 ni 3333 ISSN 1529 2916 PMC 4862588 PMID 26642356 Sun Lei Jiang Zhengfan Acosta Rodriguez Victoria A Berger Michael Du Xin Choi Jin Huk Wang Jianhui Wang Kuan Wen Kilaru Gokhul K Mohawk Jennifer A Quan Jiexia Scott Lindsay Hildebrand Sara Li Xiaohong Tang Miao November 6 2017 HCFC2 is needed for IRF1 and IRF2 dependent Tlr3 transcription and for survival during viral infections The Journal of Experimental Medicine 214 11 3263 3277 doi 10 1084 jem 20161630 ISSN 1540 9538 PMC 5679162 PMID 28970238 Shi Hexin Sun Lei Wang Ying Liu Aijie Zhan Xiaoming Li Xiaohong Tang Miao Anderton Priscilla Hildebrand Sara Quan Jiexia Ludwig Sara Moresco Eva Marie Y Beutler Bruce March 2 2021 N4BP1 negatively regulates NF kB by binding and inhibiting NEMO oligomerization Nature Communications 12 1 1379 Bibcode 2021NatCo 12 1379S doi 10 1038 s41467 021 21711 5 ISSN 2041 1723 PMC 7925594 PMID 33654074 Kim You Me Brinkmann Melanie M Paquet Marie Eve Ploegh Hidde L March 13 2008 UNC93B1 delivers nucleotide sensing toll like receptors to endolysosomes Nature 452 7184 234 238 Bibcode 2008Natur 452 234K doi 10 1038 nature06726 ISSN 1476 4687 PMID 18305481 S2CID 4397023 a b Casrouge Armanda Zhang Shen Ying Eidenschenk Celine Jouanguy Emmanuelle Puel Anne Yang Kun Alcais Alexandre Picard Capucine Mahfoufi Nora Nicolas Nathalie Lorenzo Lazaro Plancoulaine Sabine Senechal Brigitte Geissmann Frederic Tabeta Koichi October 13 2006 Herpes simplex virus encephalitis in human UNC 93B deficiency Science 314 5797 308 312 Bibcode 2006Sci 314 308C doi 10 1126 science 1128346 ISSN 1095 9203 PMID 16973841 S2CID 12501759 Blasius Amanda L Arnold Carrie N Georgel Philippe Rutschmann Sophie Xia Yu Lin Pei Ross Charles Li Xiaohong Smart Nora G Beutler Bruce November 16 2010 Slc15a4 AP 3 and Hermansky Pudlak syndrome proteins are required for Toll like receptor signaling in plasmacytoid dendritic cells Proceedings of the National Academy of Sciences of the United States of America 107 46 19973 19978 Bibcode 2010PNAS 10719973B doi 10 1073 pnas 1014051107 ISSN 1091 6490 PMC 2993408 PMID 21045126 Lazar Daniel C Wang Wesley W Chiu Tzu Yuan Li Weichao Jadhav Appaso M Wozniak Jacob M Gazaniga Nathalia Theofilopoulos Argyrios N Teijaro John R Parker Christopher G October 7 2022 Chemoproteomics guided development of SLC15A4 inhibitors with anti inflammatory activity doi 10 1101 2022 10 07 511216 S2CID 252820006 a href Template Cite journal html title Template Cite journal cite journal a Cite journal requires journal help Beutler Bruce Crozat Karine Koziol James A Georgel Philippe February 2005 Genetic dissection of innate immunity to infection the mouse cytomegalovirus model Current Opinion in Immunology 17 1 36 43 doi 10 1016 j coi 2004 11 004 ISSN 0952 7915 PMID 15653308 Beutler Bruce Eidenschenk Celine Crozat Karine Imler Jean Luc Takeuchi Osamu Hoffmann Jules A Akira Shizuo October 2007 Genetic analysis of resistance to viral infection Nature Reviews Immunology 7 10 753 766 doi 10 1038 nri2174 ISSN 1474 1741 PMID 17893693 S2CID 37705652 Croker B Crozat K Berger M Xia Y Sovath S Schaffer L Eleftherianos I Imler J L Beutler B 2007 ATP sensitive potassium channels mediate survival during infection in mammals and insects Nature Genetics 39 12 1453 1460 doi 10 1038 ng 2007 25 PMID 18026101 S2CID 41183715 Brandl Katharina Rutschmann Sophie Li Xiaohong Du Xin Xiao Nengming Schnabl Bernd Brenner David A Beutler Bruce March 3 2009 Enhanced sensitivity to DSS colitis caused by a hypomorphic Mbtps1 mutation disrupting the ATF6 driven unfolded protein response Proceedings of the National Academy of Sciences of the United States of America 106 9 3300 3305 Bibcode 2009PNAS 106 3300B doi 10 1073 pnas 0813036106 ISSN 1091 6490 PMC 2651297 PMID 19202076 Brandl Katharina Sun Lei Neppl Christina Siggs Owen M Le Gall Sylvain M Tomisato Wataru Li Xiaohong Du Xin Maennel Daniela N Blobel Carl P Beutler Bruce November 16 2010 MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands Proceedings of the National Academy of Sciences of the United States of America 107 46 19967 19972 Bibcode 2010PNAS 10719967B doi 10 1073 pnas 1014669107 ISSN 1091 6490 PMC 2993336 PMID 21041656 Brandl Katharina Tomisato Wataru Li Xiaohong Neppl Christina Pirie Elaine Falk Werner Xia Yu Moresco Eva Marie Y Baccala Roberto Theofilopoulos Argyrios N Schnabl Bernd Beutler Bruce July 31 2012 Yip1 domain family member 6 Yipf6 mutation induces spontaneous intestinal inflammation in mice Proceedings of the National Academy of Sciences of the United States of America 109 31 12650 12655 Bibcode 2012PNAS 10912650B doi 10 1073 pnas 1210366109 ISSN 1091 6490 PMC 3412000 PMID 22802641 McAlpine William Sun Lei Wang Kuan Wen Liu Aijie Jain Ruchi San Miguel Miguel Wang Jianhui Zhang Zhao Hayse Braden McAlpine Sarah Grace Choi Jin Huk Zhong Xue Ludwig Sara Russell Jamie Zhan Xiaoming December 4 2018 Excessive endosomal TLR signaling causes inflammatory disease in mice with defective SMCR8 WDR41 C9ORF72 complex function Proceedings of the National Academy of Sciences of the United States of America 115 49 E11523 E11531 Bibcode 2018PNAS 11511523M doi 10 1073 pnas 1814753115 ISSN 1091 6490 PMC 6298088 PMID 30442666 McAlpine William Wang Kuan Wen Choi Jin Huk San Miguel Miguel McAlpine Sarah Grace Russell Jamie Ludwig Sara Li Xiaohong Tang Miao Zhan Xiaoming Choi Mihwa Wang Tao Bu Chun Hui Murray Anne R Moresco Eva Marie Y September 27 2018 The class I myosin MYO1D binds to lipid and protects against colitis Disease Models amp Mechanisms 11 9 dmm035923 doi 10 1242 dmm 035923 ISSN 1754 8411 PMC 6176994 PMID 30279225 Wang Kuan Wen Zhan Xiaoming McAlpine William Zhang Zhao Choi Jin Huk Shi Hexin Misawa Takuma Yue Tao Zhang Duanwu Wang Ying Ludwig Sara Russell Jamie Tang Miao Li Xiaohong Murray Anne R June 4 2019 Enhanced susceptibility to chemically induced colitis caused by excessive endosomal TLR signaling in LRBA deficient mice Proceedings of the National Academy of Sciences of the United States of America 116 23 11380 11389 Bibcode 2019PNAS 11611380W doi 10 1073 pnas 1901407116 ISSN 1091 6490 PMC 6561264 PMID 31097594 Turer Emre McAlpine William Wang Kuan Wen Lu Tianshi Li Xiaohong Tang Miao Zhan Xiaoming Wang Tao Zhan Xiaowei Bu Chun Hui Murray Anne R Beutler Bruce February 14 2017 Creatine maintains intestinal homeostasis and protects against colitis Proceedings of the National Academy of Sciences of the United States of America 114 7 E1273 E1281 Bibcode 2017PNAS 114E1273T doi 10 1073 pnas 1621400114 ISSN 1091 6490 PMC 5321020 PMID 28137860 SoRelle Jeffrey A Chen Zhe Wang Jianhui Yue Tao Choi Jin Huk Wang Kuan Wen Zhong Xue Hildebrand Sara Russell Jamie Scott Lindsay Xu Darui Zhan Xiaowei Bu Chun Hui Wang Tao Choi Mihwa April 2021 Dominant atopy risk mutations identified by mouse forward genetic analysis Allergy 76 4 1095 1108 doi 10 1111 all 14564 ISSN 1398 9995 PMC 7889751 PMID 32810290 a b Chatenoud Lucienne Marquet Cindy Valette Fabrice Scott Lindsay Quan Jiexia Bu Chun Hui Hildebrand Sara Moresco Eva Marie Y Bach Jean Francois Beutler Bruce June 1 2022 Modulation of autoimmune diabetes by N ethyl N nitrosourea induced mutations in non obese diabetic mice Disease Models amp Mechanisms 15 6 dmm049484 doi 10 1242 dmm 049484 ISSN 1754 8411 PMC 9178510 PMID 35502705 a b Foray Anne Perrine Candon Sophie Hildebrand Sara Marquet Cindy Valette Fabrice Pecquet Coralie Lemoine Sebastien Langa Vives Francina Dumas Michael Hu Peipei Santamaria Pere You Sylvaine Lyon Stephen Scott Lindsay Bu Chun Hui November 23 2021 De novo germline mutation in the dual specificity phosphatase 10 gene accelerates autoimmune diabetes Proceedings of the National Academy of Sciences of the United States of America 118 47 e2112032118 Bibcode 2021PNAS 11812032F doi 10 1073 pnas 2112032118 ISSN 1091 6490 PMC 8617500 PMID 34782469 a b c Zhang Zhao Turer Emre Li Xiaohong Zhan Xiaoming Choi Mihwa Tang Miao Press Amanda Smith Steven R Divoux Adeline Moresco Eva Marie Y Beutler Bruce October 18 2016 Insulin resistance and diabetes caused by genetic or diet induced KBTBD2 deficiency in mice Proceedings of the National Academy of Sciences of the United States of America 113 42 E6418 E6426 Bibcode 2016PNAS 113E6418Z doi 10 1073 pnas 1614467113 ISSN 1091 6490 PMC 5081616 PMID 27708159 Turer Emre E San Miguel Miguel Wang Kuan Wen McAlpine William Ou Feiya Li Xiaohong Tang Miao Zang Zhao Wang Jianhui Hayse Braden Evers Bret Zhan Xiaoming Russell Jamie Beutler Bruce December 18 2018 A viable hypomorphic Arnt2 mutation causes hyperphagic obesity diabetes and hepatic steatosis Disease Models amp Mechanisms 11 12 dmm035451 doi 10 1242 dmm 035451 ISSN 1754 8411 PMC 6307907 PMID 30563851 a b c Zhang Zhao Jiang Yiao Su Lijing Ludwig Sara Zhang Xuechun Tang Miao Li Xiaohong Anderton Priscilla Zhan Xiaoming Choi Mihwa Russell Jamie Bu Chun Hui Lyon Stephen Xu Darui Hildebrand Sara November 1 2022 Obesity caused by an OVOL2 mutation reveals dual roles of OVOL2 in promoting thermogenesis and limiting white adipogenesis Cell Metabolism 34 11 1860 1874 e4 doi 10 1016 j cmet 2022 09 018 ISSN 1932 7420 PMC 9633419 PMID 36228616 a b Berger Michael Krebs Philippe Crozat Karine Li Xiaohong Croker Ben A Siggs Owen M Popkin Daniel Du Xin Lawson Brian R Theofilopoulos Argyrios N Xia Yu Khovananth Kevin Moresco Eva Marie Satoh Takashi Takeuchi Osamu April 2010 An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence Nature Immunology 11 4 335 343 doi 10 1038 ni 1847 ISSN 1529 2916 PMC 2861894 PMID 20190759 Siggs Owen M Arnold Carrie N Huber Christoph Pirie Elaine Xia Yu Lin Pei Nemazee David Beutler Bruce May 2011 The P4 type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow Nature Immunology 12 5 434 440 doi 10 1038 ni 2012 ISSN 1529 2916 PMC 3079768 PMID 21423172 Siggs Owen M Li Xiaohong Xia Yu Beutler Bruce January 16 2012 ZBTB1 is a determinant of lymphoid development The Journal of Experimental Medicine 209 1 19 27 doi 10 1084 jem 20112084 ISSN 1540 9538 PMC 3260866 PMID 22201126 a b Choi Jin Huk Han Jonghee Theodoropoulos Panayotis C Zhong Xue Wang Jianhui Medler Dawson Ludwig Sara Zhan Xiaoming Li Xiaohong Tang Miao Gallagher Thomas Yu Gang Beutler Bruce March 3 2020 Essential requirement for nicastrin in marginal zone and B 1 B cell development Proceedings of the National Academy of Sciences of the United States of America 117 9 4894 4901 Bibcode 2020PNAS 117 4894C doi 10 1073 pnas 1916645117 ISSN 1091 6490 PMC 7060662 PMID 32071239 a b Choi Jin Huk Zhong Xue McAlpine William Liao Tzu Chieh Zhang Duanwu Fang Beibei Russell Jamie Ludwig Sara Nair Gill Evan Zhang Zhao Wang Kuan Wen Misawa Takuma Zhan Xiaoming Choi Mihwa Wang Tao May 10 2019 LMBR1L regulates lymphopoiesis through Wnt b catenin signaling Science 364 6440 eaau0812 doi 10 1126 science aau0812 ISSN 1095 9203 PMC 7206793 PMID 31073040 a b Choi Jin Huk Zhong Xue Zhang Zhao Su Lijing McAlpine William Misawa Takuma Liao Tzu Chieh Zhan Xiaoming Russell Jamie Ludwig Sara Li Xiaohong Tang Miao Anderton Priscilla Moresco Eva Marie Y Beutler Bruce April 6 2020 Essential cell extrinsic requirement for PDIA6 in lymphoid and myeloid development The Journal of Experimental Medicine 217 4 e20190006 doi 10 1084 jem 20190006 ISSN 1540 9538 PMC 7144532 PMID 31985756 a b Zhang Duanwu Yue Tao Choi Jin Huk Nair Gill Evan Zhong Xue Wang Kuan Wen Zhan Xiaoming Li Xiaohong Choi Mihwa Tang Miao Quan Jiexia Hildebrand Sara Moresco Eva Marie Y Beutler Bruce October 2019 Syndromic immune disorder caused by a viable hypomorphic allele of spliceosome component Snrnp40 Nature Immunology 20 10 1322 1334 doi 10 1038 s41590 019 0464 4 ISSN 1529 2916 PMC 7179765 PMID 31427773 a b Zhong Xue Choi Jin Huk Hildebrand Sara Ludwig Sara Wang Jianhui Nair Gill Evan Liao Tzu Chieh Moresco James J Liu Aijie Quan Jiexia Sun Qihua Zhang Duanwu Zhan Xiaoming Choi Mihwa Li Xiaohong May 3 2022 RNPS1 inhibits excessive tumor necrosis factor tumor necrosis factor receptor signaling to support hematopoiesis in mice Proceedings of the National Academy of Sciences of the United States of America 119 18 e2200128119 Bibcode 2022PNAS 11900128Z doi 10 1073 pnas 2200128119 ISSN 1091 6490 PMC 9170173 PMID 35482923 a b Zhong Xue Su Lijing Yang Yi Nair Gill Evan Tang Miao Anderton Priscilla Li Xiaohong Wang Jianhui Zhan Xiaoming Tomchick Diana R Brautigam Chad A Moresco Eva Marie Y Choi Jin Huk Beutler Bruce April 14 2020 Genetic and structural studies of RABL3 reveal an essential role in lymphoid development and function Proceedings of the National Academy of Sciences of the United States of America 117 15 8563 8572 Bibcode 2020PNAS 117 8563Z doi 10 1073 pnas 2000703117 ISSN 1091 6490 PMC 7165429 PMID 32220963 a b Misawa Takuma SoRelle Jeffrey A Choi Jin Huk Yue Tao Wang Kuan Wen McAlpine William Wang Jianhui Liu Aijie Tabeta Koichi Turer Emre E Evers Bret Nair Gill Evan Poddar Subhajit Su Lijing Ou Feiya January 24 2020 Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation Science Immunology 5 43 eaaz0085 doi 10 1126 sciimmunol aaz0085 ISSN 2470 9468 PMC 7278039 PMID 31980486 Arnold Carrie N Pirie Elaine Dosenovic Pia McInerney Gerald M Xia Yu Wang Nathaniel Li Xiaohong Siggs Owen M Karlsson Hedestam Gunilla B Beutler Bruce July 31 2012 A forward genetic screen reveals roles for Nfkbid Zeb1 and Ruvbl2 in humoral immunity Proceedings of the National Academy of Sciences of the United States of America 109 31 12286 12293 doi 10 1073 pnas 1209134109 ISSN 1091 6490 PMC 3411946 PMID 22761313 Choi Jin Huk Wang Kuan Wen Zhang Duanwu Zhan Xiaowei Wang Tao Bu Chun Hui Behrendt Cassie L Zeng Ming Wang Ying Misawa Takuma Li Xiaohong Tang Miao Zhan Xiaoming Scott Lindsay Hildebrand Sara February 14 2017 IgD class switching is initiated by microbiota and limited to mucosa associated lymphoid tissue in mice Proceedings of the National Academy of Sciences of the United States of America 114 7 E1196 E1204 Bibcode 2017PNAS 114E1196C doi 10 1073 pnas 1621258114 ISSN 1091 6490 PMC 5321007 PMID 28137874 Yue Tao Zhan Xiaoming Zhang Duanwu Jain Ruchi Wang Kuan Wen Choi Jin Huk Misawa Takuma Su Lijing Quan Jiexia Hildebrand Sara Xu Darui Li Xiaohong Turer Emre Sun Lei Moresco Eva Marie Y May 14 2021 SLFN2 protection of tRNAs from stress induced cleavage is essential for T cell mediated immunity Science 372 6543 eaba4220 doi 10 1126 science aba4220 ISSN 1095 9203 PMC 8442736 PMID 33986151 a b Nair Gill Evan Bonora Massimo Zhong Xue Liu Aijie Miranda Amber Stewart Nathan Ludwig Sara Russell Jamie Gallagher Thomas Pinton Paolo Beutler Bruce May 3 2021 Calcium flux control by Pacs1 Wdr37 promotes lymphocyte quiescence and lymphoproliferative diseases The EMBO Journal 40 9 e104888 doi 10 15252 embj 2020104888 ISSN 1460 2075 PMC 8090855 PMID 33630350 Du X She E Gelbart T Truksa J Lee P Xia Y Khovananth K Mudd S Mann N Moresco E M Y Beutler E Beutler B 2008 The serine protease TMPRSS6 is required to sense iron deficiency Science 320 5879 1088 1092 Bibcode 2008Sci 320 1088D doi 10 1126 science 1157121 PMC 2430097 PMID 18451267 Du X Schwander M Moresco E M Y Viviani P Haller C Hildebrand M S Pak K Tarantino L Roberts A Richardson H Koob G Najmabadi H Ryan A F Smith R J H Muller U Beutler B 2008 A catechol O methyltransferase that is essential for auditory function in mice and humans Proceedings of the National Academy of Sciences 105 38 14609 14614 Bibcode 2008PNAS 10514609D doi 10 1073 pnas 0807219105 PMC 2567147 PMID 18794526 Blasius Amanda L Brandl Katharina Crozat Karine Xia Yu Khovananth Kevin Krebs Philippe Smart Nora G Zampolli Antonella Ruggeri Zaverio M Beutler Bruce A February 24 2009 Mice with mutations of Dock7 have generalized hypopigmentation and white spotting but show normal neurological function Proceedings of the National Academy of Sciences of the United States of America 106 8 2706 2711 Bibcode 2009PNAS 106 2706B doi 10 1073 pnas 0813208106 ISSN 1091 6490 PMC 2650330 PMID 19202056 Rutschmann Sophie Crozat Karine Li Xiaohong Du Xin Hanselman Jeffrey C Shigeoka Alana A Brandl Katharina Popkin Daniel L McKay Dianne B Xia Yu Moresco Eva Marie Y Beutler Bruce April 2012 Hypopigmentation and maternal zygotic embryonic lethality caused by a hypomorphic mbtps1 mutation in mice G3 Genes Genomes Genetics 2 4 499 504 doi 10 1534 g3 112 002196 ISSN 2160 1836 PMC 3337478 PMID 22540041 Chen Zhe Holland William Shelton John M Ali Aktar Zhan Xiaoming Won Sungyong Tomisato Wataru Liu Chen Li Xiaohong Moresco Eva Marie Y Beutler Bruce May 20 2014 Mutation of mouse Samd4 causes leanness myopathy uncoupled mitochondrial respiration and dysregulated mTORC1 signaling Proceedings of the National Academy of Sciences of the United States of America 111 20 7367 7372 Bibcode 2014PNAS 111 7367C doi 10 1073 pnas 1406511111 ISSN 1091 6490 PMC 4034201 PMID 24799716 a b Zhang Zhao Gallagher Thomas Scherer Philipp E Beutler Bruce May 26 2020 Tissue specific disruption of Kbtbd2 uncovers adipocyte intrinsic and extrinsic features of the teeny lipodystrophy syndrome Proceedings of the National Academy of Sciences of the United States of America 117 21 11829 11835 Bibcode 2020PNAS 11711829Z doi 10 1073 pnas 2000118117 ISSN 1091 6490 PMC 7260979 PMID 32381739 a b Zhang Zhao Xun Yu Rong Shunxing Yan Lijuan SoRelle Jeffrey A Li Xiaohong Tang Miao Keller Katie Ludwig Sara Moresco Eva Marie Y Beutler Bruce July 16 2022 Loss of immunity related GTPase GM4951 leads to nonalcoholic fatty liver disease without obesity Nature Communications 13 1 4136 Bibcode 2022NatCo 13 4136Z doi 10 1038 s41467 022 31812 4 ISSN 2041 1723 PMC 9288484 PMID 35842425 Smyth Ian Du Xin Taylor Martin S Justice Monica J Beutler Bruce Jackson Ian J September 14 2004 The extracellular matrix gene Frem1 is essential for the normal adhesion of the embryonic epidermis Proceedings of the National Academy of Sciences of the United States of America 101 37 13560 13565 Bibcode 2004PNAS 10113560S doi 10 1073 pnas 0402760101 ISSN 0027 8424 PMC 518794 PMID 15345741 Al Fadhli Fatima M Afqi Manal Sairafi Mona Hamza Almuntashri Makki Alharby Essa Alharbi Ghadeer Abdud Samad Firoz Hashmi Jamil Amjad Zaytuni Dimah Bahashwan Ahmed A Choi Jin Huk Peake Roy W A Beutler Bruce Almontashiri Naif A M May 2021 Biallelic loss of function variant in the unfolded protein response gene PDIA6 is associated with asphyxiating thoracic dystrophy and neonatal onset diabetes Clinical Genetics 99 5 694 703 doi 10 1111 cge 13930 ISSN 1399 0004 PMID 33495992 S2CID 231710148 Israel Laura Wang Ying Bulek Katarzyna Della Mina Erika Zhang Zhao Pedergnana Vincent Chrabieh Maya Lemmens Nicole A Sancho Shimizu Vanessa Descatoire Marc Lasseau Theo Israelsson Elisabeth Lorenzo Lazaro Yun Ling Belkadi Aziz February 23 2017 Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity Cell 168 5 789 800 e10 doi 10 1016 j cell 2017 01 039 ISSN 1097 4172 PMC 5328639 PMID 28235196 Melis Maria Antonietta Cau Milena Congiu Rita Sole Gabriella Barella Susanna Cao Antonio Westerman Mark Cazzola Mario Galanello Renzo October 2008 A mutation in the TMPRSS6 gene encoding a transmembrane serine protease that suppresses hepcidin production in familial iron deficiency anemia refractory to oral iron Haematologica 93 10 1473 1479 doi 10 3324 haematol 13342 ISSN 1592 8721 PMID 18603562 S2CID 23364362 a b El Hayek Lauretta Tuncay Islam Oguz Nijem Nadine Russell Jamie Ludwig Sara Kaur Kiran Li Xiaohong Anderton Priscilla Tang Miao Gerard Amanda Heinze Anja Zacher Pia Alsaif Hessa S Rad Aboulfazl Hassanpour Kazem December 22 2020 KDM5A mutations identified in autism spectrum disorder using forward genetics eLife 9 e56883 doi 10 7554 eLife 56883 ISSN 2050 084X PMC 7755391 PMID 33350388 a b Rios Jonathan J Denton Kristin Yu Hao Manickam Kandamurugu Garner Shannon Russell Jamie Ludwig Sara Rosenfeld Jill A Liu Pengfei Munch Jake Sucato Daniel J Beutler Bruce Wise Carol A June 1 2021 Saturation mutagenesis defines novel mouse models of severe spine deformity Disease Models amp Mechanisms 14 6 dmm048901 doi 10 1242 dmm 048901 ISSN 1754 8411 PMC 8246263 PMID 34142127 a b Rios Jonathan J Denton Kristin Russell Jamie Kozlitina Julia Ferreira Carlos R Lewanda Amy F Mayfield Joshua E Moresco Eva Ludwig Sara Tang Miao Li Xiaohong Lyon Stephen Khanshour Anas Paria Nandina Khalid Aysha August 2021 Germline Saturation Mutagenesis Induces Skeletal Phenotypes in Mice Journal of Bone and Mineral Research 36 8 1548 1565 doi 10 1002 jbmr 4323 ISSN 1523 4681 PMC 8862308 PMID 33905568 Andrews T D Whittle B Field M A Balakishnan B Zhang Y Shao Y Cho V Kirk M Singh M Xia Y Hager J Winslade S Sjollema G Beutler B Enders A May 2012 Massively parallel sequencing of the mouse exome to accurately identify rare induced mutations an immediate source for thousands of new mouse models Open Biology 2 5 120061 doi 10 1098 rsob 120061 ISSN 2046 2441 PMC 3376740 PMID 22724066 Bull Katherine R Rimmer Andrew J Siggs Owen M Miosge Lisa A Roots Carla M Enders Anselm Bertram Edward M Crockford Tanya L Whittle Belinda Potter Paul K Simon Michelle M Mallon Ann Marie Brown Steve D M Beutler Bruce Goodnow Christopher C 2013 Unlocking the bottleneck in forward genetics using whole genome sequencing and identity by descent to isolate causative mutations PLOS Genetics 9 1 e1003219 doi 10 1371 journal pgen 1003219 ISSN 1553 7404 PMC 3561070 PMID 23382690 Xia Yu Won Sungyong Du Xin Lin Pei Ross Charles La Vine Diantha Wiltshire Sean Leiva Gabriel Vidal Silvia M Whittle Belinda Goodnow Christopher C Koziol James Moresco Eva Marie Y Beutler Bruce December 2010 Bulk segregation mapping of mutations in closely related strains of mice Genetics 186 4 1139 1146 doi 10 1534 genetics 110 121160 ISSN 1943 2631 PMC 2998299 PMID 20923982 a b Wang Tao Zhan Xiaowei Bu Chun Hui Lyon Stephen Pratt David Hildebrand Sara Choi Jin Huk Zhang Zhao Zeng Ming Wang Kuan wen Turer Emre Chen Zhe Zhang Duanwu Yue Tao Wang Ying February 3 2015 Real time resolution of point mutations that cause phenovariance in mice Proceedings of the National Academy of Sciences of the United States of America 112 5 E440 449 Bibcode 2015PNAS 112E 440W doi 10 1073 pnas 1423216112 ISSN 1091 6490 PMC 4321302 PMID 25605905 Wang Tao Bu Chun Hui Hildebrand Sara Jia Gaoxiang Siggs Owen M Lyon Stephen Pratt David Scott Lindsay Russell Jamie Ludwig Sara Murray Anne R Moresco Eva Marie Y Beutler Bruce January 30 2018 Probability of phenotypically detectable protein damage by ENU induced mutations in the Mutagenetix database Nature Communications 9 1 441 Bibcode 2018NatCo 9 441W doi 10 1038 s41467 017 02806 4 ISSN 2041 1723 PMC 5789985 PMID 29382827 a b Xu Darui Lyon Stephen Bu Chun Hui Hildebrand Sara Choi Jin Huk Zhong Xue Liu Aijie Turer Emre E Zhang Zhao Russell Jamie Ludwig Sara Mahrt Elena Nair Gill Evan Shi Hexin Wang Ying July 13 2021 Thousands of induced germline mutations affecting immune cells identified by automated meiotic mapping coupled with machine learning Proceedings of the National Academy of Sciences of the United States of America 118 28 e2106786118 Bibcode 2021PNAS 11806786X doi 10 1073 pnas 2106786118 ISSN 1091 6490 PMC 8285956 PMID 34260399 Chen Bo Aredo Bogale Ding Yi Zhong Xin Zhu Yuanfei Zhao Cynthia X Kumar Ashwani Xing Chao Gautron Laurent Lyon Stephen Russell Jamie Li Xiaohong Tang Miao Anderton Priscilla Ludwig Sara June 9 2020 Forward genetic analysis using OCT screening identifies Sfxn3 mutations leading to progressive outer retinal degeneration in mice Proceedings of the National Academy of Sciences of the United States of America 117 23 12931 12942 Bibcode 2020PNAS 11712931C doi 10 1073 pnas 1921224117 ISSN 1091 6490 PMC 7293615 PMID 32457148 Wang Yibing Cao Liqin Lee Chia Ying Matsuo Tomohiko Wu Kejia Asher Greg Tang Lijun Saitoh Tsuyoshi Russell Jamie Klewe Nebenius Daniela Wang Li Soya Shingo Hasegawa Emi Cherasse Yoan Zhou Jiamin May 23 2018 Large scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor evoked innate fear behaviors Nature Communications 9 1 2041 Bibcode 2018NatCo 9 2041W doi 10 1038 s41467 018 04324 3 ISSN 2041 1723 PMC 5966455 PMID 29795268 Morin Matthew D Wang Ying Jones Brian T Mifune Yuto Su Lijing Shi Hexin Moresco Eva Marie Y Zhang Hong Beutler Bruce Boger Dale L October 31 2018 Diprovocims A New and Exceptionally Potent Class of Toll like Receptor Agonists Journal of the American Chemical Society 140 43 14440 14454 doi 10 1021 jacs 8b09223 ISSN 1520 5126 PMC 6209530 PMID 30272974 Morin Matthew D Wang Ying Jones Brian T Su Lijing Surakattula Murali M R P Berger Michael Huang Hua Beutler Elliot K Zhang Hong Beutler Bruce Boger Dale L May 26 2016 Discovery and Structure Activity Relationships of the Neoseptins A New Class of Toll like Receptor 4 TLR4 Agonists Journal of Medicinal Chemistry 59 10 4812 4830 doi 10 1021 acs jmedchem 6b00177 ISSN 1520 4804 PMC 4882283 PMID 27050713 Wang Ying Su Lijing Morin Matthew D Jones Brian T Mifune Yuto Shi Hexin Wang Kuan Wen Zhan Xiaoming Liu Aijie Wang Jianhui Li Xiaohong Tang Miao Ludwig Sara Hildebrand Sara Zhou Kejin September 11 2018 Adjuvant effect of the novel TLR1 TLR2 agonist Diprovocim synergizes with anti PD L1 to eliminate melanoma in mice Proceedings of the National Academy of Sciences of the United States of America 115 37 E8698 E8706 Bibcode 2018PNAS 115E8698W doi 10 1073 pnas 1809232115 ISSN 1091 6490 PMC 6140543 PMID 30150374 Wang Ying Su Lijing Morin Matthew D Jones Brian T Whitby Landon R Surakattula Murali M R P Huang Hua Shi Hexin Choi Jin Huk Wang Kuan wen Moresco Eva Marie Y Berger Michael Zhan Xiaoming Zhang Hong Boger Dale L February 16 2016 TLR4 MD 2 activation by a synthetic agonist with no similarity to LPS Proceedings of the National Academy of Sciences of the United States of America 113 7 E884 893 Bibcode 2016PNAS 113E 884W doi 10 1073 pnas 1525639113 ISSN 1091 6490 PMC 4763747 PMID 26831104 Su Lijing Athamna Muhammad Wang Ying Wang Junmei Freudenberg Marina Yue Tao Wang Jianhui Moresco Eva Marie Y He Haoming Zor Tsaffrir Beutler Bruce July 27 2021 Sulfatides are endogenous ligands for the TLR4 MD 2 complex Proceedings of the National Academy of Sciences of the United States of America 118 30 e2105316118 Bibcode 2021PNAS 11805316S doi 10 1073 pnas 2105316118 ISSN 1091 6490 PMC 8325290 PMID 34290146 Su Lijing Wang Ying Wang Junmei Mifune Yuto Morin Matthew D Jones Brian T Moresco Eva Marie Y Boger Dale L Beutler Bruce Zhang Hong March 28 2019 Structural Basis of TLR2 TLR1 Activation by the Synthetic Agonist Diprovocim Journal of Medicinal Chemistry 62 6 2938 2949 doi 10 1021 acs jmedchem 8b01583 ISSN 1520 4804 PMC 6537610 PMID 30829478 Yang Ming Hsiu Russell Jamie L Mifune Yuto Wang Ying Shi Hexin Moresco Eva Marie Y Siegwart Daniel J Beutler Bruce Boger Dale L July 14 2022 Next Generation Diprovocims with Potent Human and Murine TLR1 TLR2 Agonist Activity That Activate the Innate and Adaptive Immune Response Journal of Medicinal Chemistry 65 13 9230 9252 doi 10 1021 acs jmedchem 2c00419 ISSN 1520 4804 PMC 9283309 PMID 35767437 Eric April 24 2009 TSRI s Beutler shares America s largest prize in medicine Del Mar Times Retrieved March 9 2023 Kristoffer Furberg March 20 2015 169 nye NTNU doktorer hedret Universitetsavisa in Norwegian Archived from the original on July 14 2018 Retrieved March 25 2015 Umg laurea honoris causa al Premio Nobel Bruce Alan Beutler September 23 2019 Beutler E February 1959 The hemolytic effect of primaquine and related compounds a review Blood 14 2 103 139 doi 10 1182 blood V14 2 103 103 ISSN 0006 4971 PMID 13618370 Beutler Ernest 1971 Red Cell Metabolism A Handbook of Biochemical Methods New York Grune and Stratton Beutler E 2006 Disorders of red cells resulting from enzyme abnormalitites In Lichtman MA Beutler E Kipps TJ Seligsohn U Kaushansky K Prchal JT eds Williams Hematology New York McGraw Hill pp 603 632 Beutler E February 1961 Hematology Iron Metabolism Annual Review of Medicine 12 1 195 210 doi 10 1146 annurev me 12 020161 001211 ISSN 0066 4219 Beutler Ernest July 2006 Lysosomal storage diseases natural history and ethical and economic aspects Molecular Genetics and Metabolism 88 3 208 215 doi 10 1016 j ymgme 2006 01 010 ISSN 1096 7192 PMID 16515872 Beutler E Blume K G Bross K J Chillar R K Ellington O B Fahey J L Farbstein M J Schmidt G M Spruce W E Turner M A 1979 Bone marrow transplantation as the treatment of choice for good risk adult patients with acute leukemia Transactions of the Association of American Physicians 92 189 195 ISSN 0066 9458 PMID 398617 Piro L D Carrera C J Carson D A Beutler E April 19 1990 Lasting remissions in hairy cell leukemia induced by a single infusion of 2 chlorodeoxyadenosine The New England Journal of Medicine 322 16 1117 1121 doi 10 1056 NEJM199004193221605 ISSN 0028 4793 PMID 1969613 Beutler E Yeh M Fairbanks V F January 15 1962 The normal human female as a mosaic of X chromosome activity studies using the gene for C 6 PD deficiency as a marker Proceedings of the National Academy of Sciences of the United States of America 48 1 9 16 Bibcode 1962PNAS 48 9B doi 10 1073 pnas 48 1 9 ISSN 0027 8424 PMC 285481 PMID 13868717 Beutler Bruce Beutler Ernest December 12 2002 Toll like receptor 4 polymorphisms and atherogenesis The New England Journal of Medicine 347 24 1978 1980 author reply 1978 1980 doi 10 1056 NEJM200212123472416 ISSN 1533 4406 PMID 12479194 Beutler E Gelbart T Han J H Koziol J A Beutler B January 1989 Evolution of the genome and the genetic code selection at the dinucleotide level by methylation and polyribonucleotide cleavage Proceedings of the National Academy of Sciences of the United States of America 86 1 192 196 Bibcode 1989PNAS 86 192B doi 10 1073 pnas 86 1 192 ISSN 0027 8424 PMC 286430 PMID 2463621 Truksa Jaroslav Gelbart Terri Peng Hongfan Beutler Ernest Beutler Bruce Lee Pauline November 2009 Suppression of the hepcidin encoding gene Hamp permits iron overload in mice lacking both hemojuvelin and matriptase 2 TMPRSS6 British Journal of Haematology 147 4 571 581 doi 10 1111 j 1365 2141 2009 07873 x ISSN 1365 2141 PMID 19751239 S2CID 205266224 Du Xin She Ellen Gelbart Terri Truksa Jaroslav Lee Pauline Xia Yu Khovananth Kevin Mudd Suzanne Mann Navjiwan Moresco Eva Marie Y Beutler Ernest Beutler Bruce May 23 2008 The serine protease TMPRSS6 is required to sense iron deficiency Science 320 5879 1088 1092 Bibcode 2008Sci 320 1088D doi 10 1126 science 1157121 ISSN 1095 9203 PMC 2430097 PMID 18451267 Wailoo Keith Ernest Beutler QA Hematology org Retrieved March 9 2023 Hildebrandt Sabine Kammertons Thomas Lechner Christian Schmitt Philipp Schumann Ralf R 2019 Dr Kathe Beutler 1896 1999 Medizinhistorisches Journal 54 4 294 346 doi 10 25162 mhj 2019 0009 ISSN 0025 8431 S2CID 213008951 HANS G BEUTLER 46 PHYSICIST IS DEAD Research Aide on the Chicago U Faculty Was Spectroscopist The New York Times December 19 1942 Retrieved March 9 2023 External links Edit nbsp Wikimedia Commons has media related to Bruce Beutler Official website nbsp Works on the topic Bruce Beutler at WikisourceExternal links Edit nbsp Wikimedia Commons has media related to Bruce Beutler Bruce A Beutler on Nobelprize org nbsp including the Nobel lecture How Mammals Sense Infection From Endotoxin to the Toll like Receptors Nobel Prize Inspiration Initiative Scientific Publications All publications of articles by Bruce A Beutler listed in PubMed How we sense microbes Genetic dissection of innate immunity in insects and mammals Brief review of recent work written with Jules A Hoffmann Persistent Prospector MD Bruce Beutler by Ruth Williams 2011 Video presentation by Dr Bruce Beutler at University of Texas Discovery of TLR4 and his Nobel Prize Award displayed at Perot Museum of Nature and Science in Dallas TX Retrieved from https en wikipedia org w index php title Bruce Beutler amp oldid 1180678049, wikipedia, wiki, book, books, library,

article

, read, download, free, free download, mp3, video, mp4, 3gp, jpg, jpeg, gif, png, picture, music, song, movie, book, game, games.