Dr. Christopher B. Wilson

One major focus of work in the laboratory is the elucidation of molecular mechanisms by which functional differences between naïve and memory/effector T cells are imposed, thereby allowing them to exhibit fixed and heritable patterns of effector functions. These studies helped to define mechanisms by which interferon- g is differentially expressed in T cells, and identified a strong association between reduced DNA methylation within the interferon-g locus and capacity of T cells to produce interferon-g. The latter studies provided early evidence suggesting that programs of T cell effector function are imposed in part by epigenetic mechanisms. To address this question directly, his laboratory has created mice in which DNA methyltransferase l is ablated conditionally at different stages of T cell development. Ongoing studies support the notion that DNA methylation differentially modulates gene expression and thereby affects developmental fate and cytokine production in T-lineage cells. A second focus of work addresses mechanisms governing the development of immunity following primary infection, in particular with the intracellular pathogens Listeria monocytogenes and herpes simplex virus. We are particularly interested in the role of microbial immune evasion strategies in the biology of the infection. To explore how the innate immune system senses microbial invasion and alerts the adaptive immune system during the primary immune response, his laboratory is also exploring the specificity and mechanisms by which Toll-like receptors contribute. These studies have helped to define structural and combinatorial mechanisms that determine the specificity of Toll-like receptor recognition.