My current research objectives are directed toward understanding immune responses in vivo. Much work has been invested in determining the molecular events that drive CD4+ T helper cell differentiation in vitro as well as the critical cellular players necessary for initiating an adaptive immune response within lymphoid tissues. However, it has been difficult to address true CD4+ T helper cell biology due to a lack of experimental systems designed to access CD4+ T cell function directly in vivo.
Thus, my specific interests are developing new methods to study CD4+ T cells during the effector and memory phase of the immune response in the context of different parasitic, bacterial, and viral models of infection. I am interested in comparing the phenotype and function of CD4+ T-helper cells residing in the secondary lymphoid tissues (such as spleen and lymph nodes) to those residing at sites of infection. In particular, my goal is to understand the relationship between cytokine-producing T follicular helper cells (Tfh) and conventional T-helper type 1 (Th1), T-helper type 2, and follicular regulatory T cells (Tfr). Particular attention will be focused on elucidating the role that these functionally distinct T-helper cells play in maintaining immunologic memory, and how dis-regulation of these subsets can impact B cell lymphoma development, asthma, and autoinflammatory disease. We are also committed to understanding how exposure to microbes in early-life can influence T-helper cell differentiation, regulatory function, and disease onset. Currently our models focus on understanding how helminth colonization impacts allergic disease onset and severity.
The broad, long term goals of this research program are to understand the cellular and molecular events driving the differentiation of naïve CD4+ T cells into different T-helper cell subsets, and to investigate the function, plasticity, and cell fate decisions of these cells during a primary and secondary immune response. Elucidating the signals and events that regulate T-helper cell differentiation (i.e. Th1, Th2,Tfh, Treg,Tfr) and function (i.e. cytokine production) will have broad implications in basic CD4+ T cell biology and provide important insights that will aid in the fight against infectious disease, cancer, allergic asthma, and autoinflammatory diseases.