Modulation of T cell Signaling and Effector
Individuals in societies that are served by excellent public health and effective use of childhood vaccines are still at risk of autoimmune diseases, malignancies, inflammatory pathology associated with ingestion/inhalation of toxic substances, traumatic injury and organ failure. At least some of these conditions could be alleviated by targeted regulation of signaling pathways that control responses of effector and regulatory T cells. The immunomodulation research focus group aims to elucidate signal pathways that regulate the development and activation of CD4 and CD8 T cells and Tregs. The Osborne laboratory is at the forefront of research on Notch-dependent signaling pathways that direct Th1, Th2 and Th17 development, while the Minter laboratory is investigating signaling pathways upstream and downstream from Notch, which modulate these developmental programs. Importantly these laboratories embrace translational studies aimed at redirecting T cell responses to prevent or suppress autoimmunity in models of aplastic anemia and multiple sclerosis. The Pobezinsky/Pobezinskaya laboratory focuses on dissecting how miRNA expression is regulated and the impact of increased and decreased expression of particular miRNAs on T cell and NK cell development and function, particularly in the context of cell-mediated cytotoxicity. Cell mediated cytotoxicity is inhibited in some tumor microenvironments and as shown by the Pobezinsky laboratory is restored by blocking particular miRNAs in CD8 T cells which facilitates killing of tumor cells. This research has implications for novel strategies to control tumors.