Human Pancreas Analysis Program for Type 2 Diabetes (HPAP-T2D)

Human Pancreas Analysis Program for Type 2 Diabetes (HPAP-T2D) Abstract Building on our existing infrastructure and scientific collaborations, and the expertise gained during the first four years of the HPAP effort for Type 2 Diabetes, we have assembled five cores with expertise ranging from pancreas procurement and islet isolation to data integration. These Cores form the comprehensive and integrated Penn Human Pancreas Analysis Program – T2D. Core A will procure a spectrum of human pancreata and detailed donor medical history; isolate islets; and distribute islets and tissues to the other Cores for further analysis or processing. Core B will perform physiological phenotyping by perifusion assay, calcium imaging, and oxygen consumption on the isolated islets. Core C will process tissues using multiple modalities that will allow for analysis using advanced technologies such as multiplexed immunofluorescent staining and whole slide imaging. This Core will also archive tissues, DNA and blood for future use and deliver pathological evaluations of the tissues. Core D will perform multiple advanced modalities for the molecular profiling of isolated islets including RNAseq, and DNA methylome analysis of sorted islet cell populations; single cell ATACseq and RNAseq, flow mass cytometry for single cell quantification of more than 30 cell surface and intracellular markers, and spatial transcriptomics. Finally, Core E will assemble, annotate and maintain an open-access database for the Program and its member-researchers, and collaborate with HIRN in the sharing of data. The entire program will directed by an Executive Committee consisting of the core leaders and the contact PI, who will be the interface with HIRN and NIDDK leadership. HPAP-T2D will provide physiologic, genomic, genetic, and histological analysis of the pancreas in type 2 diabetes at unprecedented detail, share the rich data with researchers world-wide before publication, and thus enable breakthrough discoveries in our understanding of this disease that has reached epidemic levels world-wide.