Major Research Interests
Dr. Odorico’s laboratory team studies pancreatic lineage differentiation, including the differentiation of insulin-producing islet endocrine cells, from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). The work is designed to address two critical needs. First is the need to generate an unlimited supply of functional insulin-secreting beta cells to be used to replace damaged beta cells in patients with diabetes. Second is the need for a cell culture model to study, specifically, human pancreas and islet development, given known differences between humans and lower organisms and the inability to study human organ development in vivo.
In this work, we have developed an in vitro model of human pancreas development using a well-characterized protocol to differentiate pluripotent stem cells toward the pancreatic lineage. Using this model we are investigating the role of transcription factors, as well as intercellular and intracellular signaling pathways at different stages of development. We have also developed cell sorting techniques to simultaneously isolate foregut progenitor cells and eliminate the teratoma promoting ESCs from mixed differentiated stem cell populations. More recently, we are investigating the role of extracellular matrix (ECM) in regulating differentiation of pancreatic progenitors with our collaborators. We are combining innovative technologies in stem cell biology (generation of iPSCs and novel pancreatic lineage differentiation protocols) and matrix biology (perfusion and spin decellularization of tissues to produce pancreas ECM) in order to establish and characterize an in vitro system which can be used to study human pancreatic stem cell-pancreatic ECM interactions. Other projects involve using tet-Ptf1a cells, a unique cell line having inducible over-expression of Ptf1a, to investigate the role of PTF1a in pancreatic progenitor cell formation and its interaction with other transcription factors in pancreas development. Lastly, we are actively testing the ability of human ESC/iPSC-derived pancreatic progenitors to mature and function to regulate blood glucose levels in diabetic mice.