Systems analyses of autoreactive T cells in Type 1 Diabetes
Type 1 Diabetes is caused by progressive autoimmune destruction of insulin-producing pancreatic beta cells. CD4+ and CD8+ T cells play a critical role in mediating disease. In this project, we are using systems immunology approaches to understand the role of pathogenic T cells in Type 1 Diabetes in murine models and in human clinical samples. We are combining single cell RNA sequencing (scRNAseq), computational modeling, and T cell epitope discovery techniques to gain a comprehensive understanding of the landscape of autoreactive T cells. These studies will reveal novel targets of autoimmunity and help understand the mechanisms behind development of T1D.
Identification of T cell epitopes in Lupus Nephritis
Lupus nephritis is caused by the infiltration of autoreactive T cells in kidneys, followed by cytotoxicity and pro-inflammatory cytokine secretion. CD4+ T cells play a major role in pathogenesis of Lupus by direct effector function, by providing help to cytotoxic CD8+ T cells, and by promoting autoantibody formation. In this project, we are using high throughput T cell epitope discovery techniques to identify the targets of autoreactive T cells in a mouse model of Lupus. These studies will reveal novel targets of autoimmunity and help understand the role of autoreactive CD4+ T cells in Lupus.
Immune engineering using Signaling and Antigen-presenting Bifunctional Receptors
Antigen-specific immunotherapies are typically more effective, safer, and personalized. In this project, we are opening a new paradigm for antigen-specific immunotherapies by using SABRs. We will use SABRs to engineer T cells and other immune cells with the goal to modulate T cell activity towards their target cells. We will perform these experiments in various disease contexts including tumor models and autoimmune models. These studies will lead to development of a new class of cell-based immunotherapies.