Feorillo Galivo, PhD - Affiliate Profile
My project aims to discover and develop cells in the human extrahepatic biliary system (mainly the gallbladder) as a viable source of cells for replacement of pancreatic beta cells. This project is anchored on studies that organs (such as pancreas, liver, and pancreas) derived from the same germ layer can be transformed into another cell type of similar developmental origin without the need to revert back to a pluripotent phase. These direct cell conversions were accomplished by introducing transcription factors relevant to the target cell’s ontogeny. For the same reason, our group focuses on the gallbladder and the cystic duct as potentially renewable and expandable sources of autologous functional pancreatic beta cells. Normal tissue biopsies of gallbladder and cystic duct from human patients are enzymatically treated to obtain disaggregated cells for expansion and subsequent reprogramming in vitro. To convert gallbladder and cystic duct cells into beta cells in vitro, we transduce these cells with replication-defective recombinant adenoviruses encoding for various transcription factors of significant roles in pancreatic beta cell lineage differentiation and which were also shown to be operative in reprogramming of insulin-producing cells. To fully assess the most important requirements for full reprogramming, I am optimizing culture conditions, vector transduction, posttranscriptional and whole cell functionality assays, and testing various combinations and stoichiometries of both positive and negative regulators of pancreatic development. Ultimate goal of this project is to demonstrate that these reprogrammed cells can survive long-term and more importantly, correct hyperglycemia in a glucose-responsive manner in vivo.
Beta cells, Pancreas, Reprogramming, Gallbladder