Research Area
Diabetes

Grant Type
Network

Year
2006

Abstract

Goal: To employ biochemical methods to recapitulate pancreatic development and understand the molecular mechanisms driving the genesis of functional insulin-producing cells from pluripotent human embryonic stem cells (hESC).

Project 1. Differentiation of pancreatic endocrine cells. Modeling embryonic pancreas development, hESCs and pancreatic progenitor cells will be differentiated into insulin-producing cells using gene transfer experiments, inducible factors, and specific receptor-ligand interactions. Additionally, the role of micro RNAs will be examined to determine how these regulatory RNAs control differentiation and pancreas development.

Project 2. An integrated signaling and proteomics-based approach to progenitor cell differentiation. Existing protein expression profiles for hESC and human fetal/adult islets will serve as templates to determine how changes in signal transduction are correlated with changes in protein expression. The objective is to link temporal activation of signaling pathways with global changes in protein expression.

Project 3. Molecular regulation of -cell epithelial to mesenchymal transition. The role of CtBP, an adaptor protein that mediates the transition of a β-cell from growth to differentiation, will be examined. Specifically, the objective is to identify the targets of CtBP and determine how these targets execute the molecular transition from an epithelial to mesenchymal phenotype.

Project 4. Neural chemotrophic factors in islet cell development. We hypothesize that the emergence and development of specific pancreatic cell lineages are coordinated through the interaction of cells with Netrins. The objective is to determine how Netrins contribute distinct developmental cues for developing adhesive/migratory functions and exert instructive roles for growth and/or differentiation pancreatic cell populations.