Funded Projects

Primary Sjögren’s Syndrome (pSS) is a chronic autoimmune disease characterized primarily by destruction of the salivary and lacrimal glands, resulting in the loss of secretory function. Currently, there is no cure for pSS and treatment options are limited due to a lack of our overall understanding of this disease. Therefore, there is a critical need to identify key pathways and mediators that are important in disease pathogenesis in the hope to facilitate earlier diagnosis and to mitigate the progression of this debilitating syndrome. In addition to the established role for abnormal immune cell responses contributing to this disease, emerging evidence suggests a functional role for epithelial cells in driving autoimmune responses by mediating recruitment, activation and differentiation of immune cells. However, the topological map of the specific niche in which subtypes of various epithelial and immune cells co-exist and crosstalk with each other is unknown. To investigate this, we will utilize a well-characterized mouse model that displays faithful recapitulation of human SS and perform Spatial Transcriptomics (ST) analysis of affected salivary glands to spatially map RNA-seq transcript data onto high-resolution tissue images. This approach will provide critical insight into the distinct epithelial and immune sub-populations of cell types associated with the various stages of SS disease progression. More specifically, these studies will allow us to obtain detailed expression signatures and a more informed understanding of the pathological transitions associated with pSS. Furthermore, we will integrate our ST based findings with our scRNA-seq transcriptomic datasets generated from this mouse model. Our results have broad implications for the identification of new biomarkers and therapeutic targets not only for pSS, but may offer mechanistic insights for other autoimmune diseases with similar etiology.