The overall goal of the Means lab is to understand the role of EGFR (epidermal growth factor receptor) signaling in pancreatic development and disease.
By using mouse models to manipulate EGFR signaling up or down, the Means lab has found a role for this signaling pathway in coordination of epithelial and mesenchymal development. Similarly, in the adult mouse pancreas, EGFR activation induces widespread stromal changes (fibrosis) in conjunction with epithelial metaplasia or neoplasia. Lab members are currently determining if the effects on epithelium and mesenchyme are each direct responses to EGFR activation or if one tissue responds indirectly via signals produced by the other tissue. To understand how EGFR signaling affects cell fates, they are tracing the cells of origin for both fibrosis and the cancer itself. Using genetic lineage tracing, they are determining the fate of acinar cells, duct cells and different mesenchymal cells in the development of pancreatitis (benign disease) or of pancreatic cancer.
Because fibrosis is a poorly understood process, the lab is determining if there are significant variations between benign and malignant disease. Cancer-associated fibrosis is thought to play a major role in preventing chemotherapeutics from reaching tumor cells. Understanding how it arises will provide crucial information for more effective treatment of pancreatic cancer.