Richard A. Flavell

Yale University


Primary Section: 43, Immunology and Inflammation
Secondary Section: 26, Genetics
Membership Type:
Member (elected 2002)

Research Interests

My research is centered on the function of eukaryotic genes and the consequences of their mutation on human and animal biology. My initial work established the discontinuous structure of the beta-globin gene and defined mutated forms of these genes in human patients with thalassemia. My laboratory pursued early studies using transfection into animal cells to determine the consequences of structural and regulatory mutations in globin genes. Our cosmid libraries made it possible to study more complex gene families, including the major histocompatibility complex (MHC). We elucidated the molecular organization of the multigene family and determined the molecular basis of MHC polymorphism, which is intergenic transfer of genetic information. We turned then to ways the immune function could be studied in genetically modified animals. Applying transgenesis and gene targeting, we made insights into molecular mechanisms underlying the immune response. Our studies have focused on cell fate decisions made between different T lymphocyte populations and have identified transcription factors responsible for these decisions. We have elucidated the function of caspases in the apoptotic process, which has led to the identification of several pathways of cell death in the immune and central nervous systems. Using genetically manipulated animal models, my laboratory has addressed the underlying mechanisms of autoimmune diseases. We have found that inflammatory responses impact strongly on the development of autoimmune disease and that regulatory mechanisms prevent autoimmunity under normal circumstances.

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