Multiple voids exist in our understanding key aspects of type 1 diabetes (T1D) pathogenesis due in large part to the paucity of pancreatic specimens and/or living islets from those with the disease, alongside a lack of experimental methodologies to comprehensively define the functional and molecular properties of human ? cells and other islet cells. To address the dual needs of organized procurement and studies of human pancreatic tissues, this application seeks to establish the Human Pancreas Procurement and Analysis Program (HPPAP) to allow investigators to use emerging technologies to understand the functional characteristics and molecular signatures of the pancreas and islets in individuals with T1D. To meet this endeavor, our interdisciplinary team brings: a) proven infrastructure and expertise to identify, collect, process, and distribute human pancreata from individuals with new-onset T1D or at high-risk for T1D; b) procedures and expertise in collecting and phenotyping the pancreas and islets in ways that will allow application of new and emerging technologies to study the functional and molecular state of human pancreatic islets; c) experience and expertise in database creation and integration for complex biologic research efforts that will allow curation and integration of data from a range of experimental platforms; and d) administrative and scientific leadership that is familiar with T1D and research pertaining to islet cell biology, pathogenesis, and immunology. Based on existing infrastructure and expertise, our HPPAP team will provide all of RFA-15-027 suggested HPPAP activities with little to no start up time through rapid implementation of proven procedures. We propose these Specific Aims: 1) Collect, process, and ?deeply phenotype? the pancreas and isolated islets from individuals with recent-onset T1D and those at high-risk for T1D; 2) Establish procedures and mechanisms to share the phenotyped specimens with scientists interested in applying emerging technologies to understand T1D; 3) Create a comprehensive, open-access, searchable, and integrated database and reference resource (HuPANC) for the community of scientists interested in understanding the T1D pancreas and islet; and 4) Enhance, strengthen, and leverage existing partnerships with programs such as IIDP, nPOD, and HIRN. Moreover, our HPPAP efforts, while independent from IIDP and nPOD, will complement those entities and the HIRN. In sum, the proposed HPPAP program will generate new resources and datasets that will allow investigators to apply new and emerging technologies to unique tissues to make discoveries regarding factors contributing to ? cell death, and facilitate the development of new strategies for the prevention and treatment of T1D.
This project will establish infrastructure and ways to study the human pancreatic islet and insulin-producing cells in order to understand how type 1 diabetes develops. By bringing together scientists from several disciplines, our group will enable scientists to apply the latest technologies to study how the insulin-producing cells are destroyed in this form of diabetes with the goal of preventing this process and type 1 diabetes.
| Hart, Nathaniel J; Aramandla, Radhika; Poffenberger, Gregory et al. (2018) Cystic fibrosis-related diabetes is caused by islet loss and inflammation. JCI Insight 3: |
| Saunders, Diane C; Brissova, Marcela; Phillips, Neil et al. (2018) Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic ? Cells for In Vitro and In Vivo Analysis. Cell Metab : |
| Brissova, Marcela; Haliyur, Rachana; Saunders, Diane et al. (2018) ? Cell Function and Gene Expression Are Compromised in Type 1 Diabetes. Cell Rep 22:2667-2676 |
| Aamodt, Kristie I; Powers, Alvin C (2017) Signals in the pancreatic islet microenvironment influence ?-cell proliferation. Diabetes Obes Metab 19 Suppl 1:124-136 |
