My research program is focused on understanding molecular and cellular mechanisms governing the pathogenesis of pancreatic ductal adenocarcinoma. While molecular pathology and cancer genetics studies have provided an outline of the cellular perturbations associated with this malignancy, the current picture remains static with only correlative links to underlying biology. I have developed a series of engineered mouse models of pancreatic adenocarcinoma harboring the signature gene mutations of the human disease—Ink4a/Arf, Kras, Smad4, p53 and Lkb1.
I am employing these models in an attempt to develop a more direct mechanistic view of how classical lesions influence PDA biology. In this regard, several questions are paramount such as what is the cell-of-origin of PDA, what are the roles of specific lesions in the tumorigenic program and how does the cell(s)-of-origin’s developmental state influence the activity of a cancer-relevant genetic lesion. Such genotype-phenotype and cell-of-origin information is critical to understanding the biology of pancreatic adenocarcinoma and has a direct impact on the selection of drug targets for chemoprevention and chemotherapy.