Date of Award
Doctor of Philosophy (PhD)
Cell replacement therapy for severe diabetes is a promising strategy to restore long term normoglycemia. With limited availability of cadaveric islets from compatible donors, cellular engineering via human pluripotent stem cells differentiation to insulin-secreting stem cell derived islets (SC-islets) provides a useful alternative as they can be generated in unlimited supply. Nonetheless, SC-islets generated with current protocols are not as well performing when compared to native human islets due to poor β cell yields and low mature β cell genes expression. Herein, I use single-cell technologies and bioinformatics to uncover mechanisms associated with pancreatic development to recapitulate β cell differentiations. Gene regulatory network modifications were done using soluble factors and gene editing tools to develop methodologies for generating mature islets from stem cells.
Michael Vahey, Maria Remedi, Jing Hughes, Irfan Lodhi,
Available for download on Wednesday, May 15, 2024