Transcription must be tightly regulated in cells to maintain appropriate gene expression levels. The pancreatic and duodenal homeobox 1 (Pdx1) is a transcription factor that coordinates the dynamic assembly of complexes essential for the function of pancreatic β-cells. Recent evidence suggests that disruption of these complexes contributes to the molecular basis for type 2 diabetes and maturity onset diabetes of the young (MODY); related to its role in development, dysregulation of Pdx1 is associated with pancreatic cancer. Mechanistic studies of this essential protein have not kept up with advances in understanding of its central role in pancreatic health.
Our efforts toward understanding Pdx1 regulation are organized into two major projects, discussed below. We are actively seeking a new postdoctoral associate and new graduate students interested in research related to these two general areas.
Project 1: Characterize the role of SPOP in glucose-dependent regulation of Pdx1 stability.
Pdx1 activity is down-regulated by the E3 substrate adaptor protein SPOP. This page is still under construction and more details should appear soon.
Project 2: Evaluate the mechanism of Set7 recruitment by Pdx1.
Pdx1 stimulated gene transcription is co-activated by interactions with the methyltransferase Set7. This page is still under construction and more details should appear soon.
This project is supported by NIH grant R01 DK121509