My laboratory is interested in exploring how pancreatic beta cells function, how they are formed during development, and how their dysfunction contributes to the development of diabetes. As a model system for these studies we make extensive use of genetically-altered mice which we derive using multiple different methods, including the recently described CRISPR/Cas9 system. Currently we pursuing three distinct but complementary projects.

First, we are studying how inflammation may affect the ability to reprogram pancreatic acinar cells into new, insulin secreting beta cells. Towards this end we have developed mice in which the expression of key beta cell reprogramming factors can be induced in both a drug and cell type-specific manner.

Second, we are exploring how excitatory stress leads to the loss of beta cell identity and function. These experiments utilize mice that lack ATP-sensitive potassium channels, and thus are chronically hyperstimulated independent of the blood glucose concentration, as well as lineage tracing methodologies so as to be able to follow the fate of beta cells over time.

Third, we are exploring the gene regulatory network that is established during development, and how specific transcription activate genes involved in progenitor cell migration, proliferation and hormone expression. This projects utilizes mice that express a GFP-Cre fusion protein that has been placed under control of the Insm1 gene and well as both RNA-seq and ChIP-seq technologies.