Richard Flavell is co-discoverer of introns in cellular genes: he showed DNA methylation correlates inversely with, and prevents, gene expression. He was the first to develop reverse genetics as a postdoc with Weissmann and in his own lab continued in this field throughout his career; he is a pioneer in the use of this approach in vivo to study function. Dr. Flavell’s laboratory studies the molecular and cellular basis of the immune response. He has been instrumental in discovering the molecular basis of T-cell differentiation from precursor cells into differentiated subsets. This work led to the discovery of GATA3 as a critical regulator of the Th2 response and the first example of such a molecule in Th cell differentiation. He went on to demonstrate the first case of regulation of gene expression in trans, via ”chromosome kissing.” Moreover his laboratory has elucidated the mechanisms of immunoregulation which prevent autoimmunity and overaggressive responses to pathogens. Specifically, Dr. Flavell's laboratory has elucidated the role of TGF-β in the regulation of immune response. This work is of relevance both to the control of autoimmune disease and the evasion of immune response by tumors. Dr. Flavell’s laboratory has discovered the role of several receptor families in the innate immune response, including the role of several Toll-like receptors and intracellular Nod-like receptor families (NLRs). This has recently led to the elucidation of function of Nod2 in inflammatory bowel diseases and Nlrp proteins in the production of IL-1. Most recently he has established a fascinating connection between inflammasomes, microbial homeostasis and chronic diseases. He showed that inflammasome dysfunction causes dysbiosis of the microbiota which, in conjunction with a susceptible diet, leads to IBD and Metabolic Syndrome, including Obesity, Fatty Liver disease and Type 2 diabetes.