Position title: Director, Islet Core; Professor of Surgery
My laboratory studies pancreatic lineage differentiation from pluripotent stem cells, including ESCs and induced pluripotent stem cells (iPSCs). The work is designed to address two critical needs: the need to generate an unlimited supply of functional insulin-secreting beta cells to replace those destroyed in patients with diabetes, and the need for a culture-based model system to study, specifically, human pancreas and islet development. We have pioneered an in vitro model of human pancreas development and continually improved protocols for differentiating pluripotent stem cells towards pancreatic lineages, resulting in glucose- responsive insulin producing islet-like clusters. Realizing the importance of organ-specific extracellular matrix (ECM) in cell fates, we have recently developed novel methods for decellularizing human pancreatic tissue and have successfully produced a hydrogel which affords the opportunity to study the matrisome and matrix/stem cell-derived islet/human islet interactions. In collaboration with the lab of Dr. Lingjun Li in the UW School of Pharmacy we are studying the matrisome and proteome of normal human pancreas from fetal stages through old age. Recently we showed that combining human pancreatic hydrogel with human cadaver islets in culture improves the phenotype and function of the cells. We are also studying whether and how pancreatic ECM hydrogel can improve the maturation and function of stem cell-derived islet organoids.