Instability of beta cell proliferation as a trigger of the innate immune system in type 1 diabetes

Goal of this project is to develop small 3D microphysiological systems devices that surpass currently available systems in physiological relevance using compartmentalized beta cells and circulating immune cells separated by a layer of endothelial cells. This system will be used to define the conditions that determine the recruitment of immune cells that mediate the sequential phases of autoimmune assault on beta cells. The PI’s hypothesis is that the earliest signals leading to the recruitment of immune cells originate form genome instability resulting from replication-transcription conflicts at highly transcribed genes, such as insulin, in highly proliferating cells. The PI proposes that activation of the cGAS-STING and TLR9 pathways by damaged DNA results in the production of chemokynes. Streamlined production of cellular components into miniature and personalized microphysiological devices will provide a powerful and affordable precision medicine platform to evaluate drugs and perform diagnostic testing.