Elucidating and manipulating the role of the Unfolded Protein Response (UPR) to improve outcomes of stem cell-derived pancreatic islet transplants

Diabetes is a metabolic disorder characterized by the inability of patients to manage blood glucose levels because of insufficient insulin production. Insulin is secreted by Beta cells localized to islets in the pancreas. Injection of insulin is required to manage diabetes in some patients, requiring frequent blood glucose monitoring. Regenerative medicine approaches are being developed as an alternative in which pancreatic islets are transplanted into patients to restore autonomous insulin secretion. Stem cell-derived pancreatic islets (SC islets) have the potential to provide an unlimited supply of islets for transplantation. My research aims to improve SC islet transplants by improving our ability to generate SC islets in the lab and their longevity after transplantation. I will develop tools to study cellular pathways that allow cells to manage high secretion levels and perform studies to better understand the role of these pathways in generating SC islets and their survival. I will then use these findings to inform strategies to improve SC islet generation and longevity. The increased accessibility and success of SC islet transplants will drastically improve the health and quality of life of patients seeking these treatments.