Human Pancreas Analysis Program for Type 1 Diabetes - HPAP-T1D

University Of Pennsylvania, Philadelphia PA

Investigators

Linked publications, trials & patents

Abstract

Human Pancreas Analysis Program for Type 1 Diabetes (HPAP-T1D) Abstract Building on the extensive existing infrastructure and scientific collaborations within the Human Pancreas Analysis Program for T1D (2017 – present), we will continue and expand the work and technology of our six cores to advance research in human type 1 diabetes (T1D). Core A will procure human pancreata, immune tissues, and detailed donor medical histories from T1D, non-diabetic but autoantibody-positive (AAb), and control donors; collect immune tissues and isolate islets; and distribute high-quality islets, tissues and cells to the other Cores for further analysis or processing. Core B will perform rigorous physiological phenotyping by perifusion and oxygen consumption assays on the isolated islets, and single islet measurements of intracellular calcium, as well as implement newer technologies to study cell composition. Core C will perform sophisticated immune profiling in spleen and lymph nodes by cell type mapping with differential gene expression and chromatin accessibility analysis, generation of a memory B cell and T cell clonal atlas across different tissues, and specificity analysis on circulating antibodies and selected T and B cell receptors. Core D will perform multiple advanced modalities for the molecular profiling of isolated islets including RNA-seq and DNA methylome analysis of sorted islet cell populations; single cell ATAC-seq and RNA-seq, flow mass cytometry for single cell quantification of more than 30 cell surface and intracellular markers, and spatial transcriptomics. Core E will process all tissues using multiple fixation modalities, cmduct pathology analysis, and biobank remaining pancreatic tissues. Core E will also perform advanced tissue morphometry, including highly multiplexed immunofluorescent imaging using CODEX. Finally, Core F will assemble, annotate, maintain and upgrade an extensive open-access database (PANC-DB) for the program and its member-researchers, and collaborate with HIRN in the sharing of data. The entire program is directed by an Executive Committee consisting of the core leaders and the contact PI, who will interface with HIRN and NIDDK leadership. Taken together, HPAP-T1D will provide physiologic, genomic, genetic, immunologic and histologic analyses of the pancreas and immune- associated tissues in T1D and share these comprehensive, integrative and robustly quality controlled data with researchers world-wide.