Conference Speaker

Bruce A. Beutler, MD Director, Center for the Genetics of Host Defense; Regental Professor; Raymond and Ellen Willie Distinguished Chair in Cancer Research, University of Texas Southwestern Medical Center, Dallas, Texas

Early in his career Bruce Beutler purified mouse TNF to homogeneity and discovered its lethal inflammatory effects. He then created a reagent for the neutralization of TNF by fusing the TNF receptor to an IgG heavy chain. As Enbrel, this molecule found clinical use in millions of patients suffering from rheumatoid arthritis and other inflammatory diseases. Seeking to understand how TNF was induced by LPS, and more generally, how microbes of all kinds were sensed by the innate immune system, he used forward genetics to find the LPS receptor. He discovered that mutations in Toll-like receptor 4 (TLR4) completely prevented LPS signaling in mice and inferred that TLR4 was the signaling core of this receptor. In 2011 he was awarded the Nobel Prize in Medicine for “studies related to the activation of innate immunity.”

Beutler has used ENU mutagenesis extensively to create new phenotypes in mice, principally affecting immunity but also metabolism and behavior. He invented a high-speed positional cloning platform known as automated meiotic mapping or AMM, which permits instantaneous determination of which mutation causes any observed phenotype. Combining mutagenesis with AMM, he and his group created robust monogenic cancer resistance phenotypes in mice. Some of the causative mutations indicate targets for drug discovery.