Pancreas development is an intricately coordinated process that involves a multitude of signaling and transcriptional processes. Much of our understanding of pancreatic development is primarily through the use of mouse models. We are improving our understanding of human pancreas development by combining stem cell models, integrative single-cell omics and genome editing to elucidate the species-specific genome regulatory landscapes governing human pancreatic endoderm and islet cell differentiation.
We are working to identify and dissect the role of regulatory switches and signaling pathways critical for islet cell maturation. Using CRISPR tools that enable efficient genome editing and transcriptional regulation, we are engineering genetic perturbations in SC-islets to characterize the molecular mechanisms behind terminal differentiation of islet cells.
The combination of stem cell differentiation protocols with precise genome editing tools has enabled us to model the molecular mechanisms behind coding and non-coding genetic defects causing diabetes. However, directed differentiation protocols employ cocktails of signaling cues that may bypass important developmental processes. As this can preclude accurate modelling of critical events in the differentiation and physiology of pancreatic islets, we are devising alternative protocols that would resemble more faithfully the natural course of islet development.