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Kirken, Robert
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overview
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The goal of the laboratory is to understand the intracellular signaling pathways responsible for mediating T cell activation so that rational strategies to regulate immune responses can be achieved. To accomplish this objective it is necessary to first understand the mechanisms through which these cells are activated. It is clear that T cell activation requires engagement with antigen, costimulatory molecules, and intercellular signaling peptides called cytokines. One cytokine we are particularly interested in is interleukin 2 (IL2). IL2 belongs to a family of cytokines that utilize a shared receptor subunit referred to as the IL2 receptor common gamma (g) chain, or gc. This receptor is recruited by one of several cytokines, which then activate a select member of the Janus tyrosine Kinase (JAK) family, JAK3. JAK3 plays a key role in the development and function of T cells. However, the intracellular molecules activated by JAK3 are not readily known nor the genes it regulates. Therefore, the laboratory is focused on identifying and characterizing these signaling proteins to better understand this event. We are particularly interested in a family of gene regulating molecules known as signal transducers and activators of transcription (Stats) and several ongoing studies in the laboratory are examining the role that Stat5a and Stat5b perform in regulating T cell activity and disease. Through critical analysis of these signaling pathways it will be possible to utilize pharmaceuticals to manipulate these secondary messengers and subsequently modulate an immune response. Ultimately, these studies will enable us to develop novel immunomodulatory drugs with therapeutic potential against important clinical conditions such as cancer, graft-versus-host disease, allergy, and autoimmune disorders
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