Islet Development

Multicellular organisms like ourselves start from a single cell; but in a highly orchestrated progression that cell multiplies and differentiates to produce all the distinct cell types that provide the structure and function of the adult organism. Our group focuses on a single cell type, the insulin-producing beta cell in the islets of Langerhans in the pancreas, and on the process by which the beta-cells differentiate from other cell types during development, and regeneration. We want to discover the route by which progenitor cells progress to mature beta-cells, and understand the mechanisms that direct cells along that route.

Despite progress in understanding islet development, important unanswered questions remain:

What cells function as the progenitors of the islet cells during development, during normal islet cell turn-over, and during islet regeneration after pancreatic damage? At what point in the maturation of islet cell progenitors do the cells become determined to become beta-cells? What signals and what genes control beta-cell fate determination? How do the beta-cell fate determination genes function? Can we use these genes to produce beta-cells for people with diabetes?

We approach these questions from several directions, by identifying and characterizing islet transcription factors, by using genetic and in vitro methods to trace the fates of cells during development, and by applying microarray technology to understanding genome-wide changes in gene expression.