This CBDS program will establish an in situ RASL-Seq Islet Study Facility that will validate a novel in situ RASL-Seq platform for diabetes research using FFPE tissue from normal and Type 1 diabetes (T1D) diseased pancreas, and then apply this platform to address the gap in available methodology to take full advantage of T1D organ repositories such as nPOD in the effort to derive molecular profiles of individual -cells and cells of other types associated within the islet that are involved in the onset of silent T1D and disease progression. We will measure gene expression profiles from individual cells, and from this data identify biomarkers and gene expression phenotypes of silent T1D compared to more advanced stages of disease. We will exploit “big data” to apply pathway analysis to the gene expression results in order to identify putative molecular mechanisms of silent T1D and disease progression, providing a basis for the development of novel therapeutic approaches. We will test matched serum to identify useful biomarkers of silent T1D from this accessible tissue, and potentially to provide the capability to divide patients into subgroups based on prognostic outcome of whether disease will progress or not.