Charles King, PhD
Assistant Research Scientist
The Whittier Institute for Diabetes
University of California, San Diego
La Jolla, CA
Project Title: "Proteomics and Endocrine Progenitor Cells"

The generation of insulin-producing Beta (ß) cells from pancreatic progenitor cells or human embryonic stem cells would provide a cell-based therapy for Type I diabetes. The process of differentiation is exquisitely controlled and each step is associated with changes in protein expression and signal transduction. The coordinated sum of these biochemical changes defines the difference between progenitor cells and ß cells. Our preliminary results identified large changes in protein expression patterns between ß cells and expanded islets, proliferating ß cells that no longer produce insulin.

We hypothesize that the proteomics-based methods of two-dimensional (2D) electrophoresis and mass spectrometry can be used to map and identify global changes in protein expression patterns and monitor changes in specific signal transduction pathways in mature ß and expanded cells.

Initially, we will apply these proteomics-based technologies to identify and classify proteins from pure preparations of ß cells. Subsequently, we will apply these techniques to study the role of the PtdIns 3-kinase (phosphatidylinositol 3-OH kinase)/PDK-1, a protein kinase that phosphorylates and activates other protein kinases. Understanding global changes in protein expression and regulation of signal transduction pathways will provide us with a better knowledge of the cues cells use during differentiation and will allow us to better manipulate progenitor cells to become ß cells.