The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awarded a $1,201,988 Cooperative Agreement to Yale University under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847). The 2-year project, running from January 1, 2025 to December 31, 2026, aims to develop advanced pancreatic-immune organoid models to study type 1 diabetes (T1D) subtypes and therapeutic responses.
The research will characterize and analyze pancreatic organoids derived from 16 existing and 20 additional patient-derived induced pluripotent stem cells (iPSCs) - 10 from T1D patients and 6 from healthy controls. Autologous islet autoantigen-reactive CD8+ T cell lines will also be prepared from the iPSC donors. The project will validate the organoid models for detecting B cell killing, analyze metabolic function and responses to inflammatory mediators, and screen for molecules that can prevent organoid damage and death. This work seeks to identify B cell intrinsic features that determine T1D progression and responses to therapies, with the goal of informing the development of more effective treatments to arrest autoimmunity and restore metabolic function.
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