We study pancreas development and regeneration. We are especially interested in signaling pathway mediated cell fate decisions in the pancreas, with emphasis on Notch and Wnt signaling. Wnt signaling in pancreatic progenitor growth and differentiation Wnt signaling is a well-conserved signaling pathway involved in the growth and homeostasis of multiple organs. Also, deregulation of Wnt signaling is the basis for a number of pathologies. We have previously shown that Wnt signaling regulates morphogenesis and growth of pancreatic progenitor cells during development. We found that while Wnt is required for the growth of pancreatic progenitor cells, hyper-activation of the pathway does not lead to organ hyperplasia, but instead interferes with pancreatic epithelial-mesechymal interaction leading to organ dysmorphogenesis.
In this current project is aimed at:
(i) Defining the mechanism through which Wnt signaling orchestrates a balance between differentiation and maintenance of the pancreatic progenitor cell state.
(ii) The role of Wnt signaling in maintaining homeostasis in the adult pancreas, and how it’s deregulation underlie pathogenesis in the pancreas.
Role of Notch signaling in differentiation of insulin producing beta-cells Pancreatic endocrine cells, including insulin-producing beta cells differentiation from a bi-potent progenitor cells population following the loss of Notch signaling. Regarding the differentiation of pancreatic endocrine cells, Notch signaling is known to inhibit the expression of the pro-endocrine transcription factor Neurogenin3 (Ngn3) through transcriptional repression. However our previous studies suggest that Notch signaling also operates to inhibit endocrine cell differentiation through post-translational control of key factors for endocrine cell differentiation. The current project is aimed at: Determining the post-translational mechanism through which Notch signaling inhibit endocrine cell differentiation in the pancreas.