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Our lab uses new technologies to couple rapid identification of interesting genes with methods to study the consequences of their expression in an organismic context. We have developed an efficient type of expression cloning of signal transduction intermediates allowing us to rapidly identify cDNAs encoding genes that engage a number of known transduction pathways as well as systems for rapid generation of mice bearing targeted disruptions of specific candidate genes. We are working on improvements of the approach to facilitate the rapid construction of conditionally defective alleles. The pathways on which we have focused most heavily are those arising from the T cell antigen receptor and other activating receptors, such as those for tumor necrosis factor alpha and lipopolysaccharide.
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