The main goal of our group is to understand the mechanisms of pancreatic growth after birth in both rodents and humans in order to regulate generation of new beta cells and expansion of beta cells for regenerative purposes.
Description of Research
Our research has focused on the islets of Langerhans , in particular: 1) their architecture and its implications for function; 2) the in vivo regulation of beta cell mass; and 3) the factors involved in islet growth and differentiation. Current areas of interest include:
1. Defining the cells in the duct that can give rise postnatally to new islets
Our studies on pancreatic regeneration in the adult rat defined two pathways of new beta cell formation in postnatal life: replication of preexisting beta cells and differentiation from progenitors/stem cells (neogenesis). Our hypothesis has been that, in the adult, pancreas duct cells act as progenitors, such that the mature duct cell regresses to a less differentiated cell and regains its potential to differentiate into an islet, an acinar, or a mature duct cell. We are defining the cells involved and the factors that are carefully orchestrated in vivo to stimulate the growth and differentiation of the beta cells.
2. Understanding the phenotypic basis of functional heterogeneity among beta cells whether normal, immature, aged, or dysfunction due to glucose toxicity
We have been interested in the specializations that determine the beta cell phenotype and how this phenotype changes through the lifetime of the cell. Our earlier focus was on what drives the immature beta cell to become functionally mature; now we are defining the heterogeneity of the beta cells in the adult.
3. Understanding how the human pancreas responds to the demand for more beta cells
We study pancreas from non-diabetic and long-term diabetic humans to assess whether the human pancreas has the same mechanisms of growth and differentiation as in the rodent pancreas.