Grant: Doctoral: Vanier Canada Graduate Scholarships

Supervisor: Patrick MacDonald, University of Alberta Background: Type 1 diabetes (T1D) occurs when the body's immune system destroys the insulin-producing ß-cells in the pancreas. For patients with a more severe form of T1D, insulin injections can behave unpredictably, and blood sugar fluctuations can lead to death. Patients who require intervention may be candidates to receive transplants of ß-cells from human organ donors. Limitations in organ donor availability prevent this treatment from being widely available. Introduction: Recently, there has been a push toward using stem cell-derived ß-cells (SCßs) to overcome these limitations. However, current protocols to produce SCßs fail to display appropriate insulin release and are functionally immature. Properties of primary insulin-producing ß-cells include sugar-regulated electrical activity and insulin granule release. To generate functional cells for transplantation, I will conduct an in-depth characterization of these properties in SCßs and compare them to primary human ß-cells to understand what differences lead to immature cells. Research Aims: (1) How do SCßs compare to primary human ß-cells in function? I will first assess the electrical function and gene expression of the SCßs necessary for insulin release. (2) what controls maturity and when it appears during SCß maturation? Changing gene expression allows SCßs to pass through maturity stages, I will assess functionality and gene markers in each stage. (3) How can we improve future differentiation protocols for clinically useful cells? I will verify the maturity markers previously found by using drugs and transplant studies. Significance: My research impacts the basic understanding of stem cells derived insulin-producing cells and identifies potential molecules and targets to improve SCßs. This real-world impact on transplantation and the knowledge generated here will be critical to creating functional stem-cell transplants for patients with T1D.