The grim prognosis for pancreatic ductal adenocarcinoma (PDAC) patients impels an improved understanding of disease biology to facilitate the development of enhanced therapies. PDAC often features a remarkably dense stroma established and populated by a pronounced population of cancer associated fibroblasts (CAFs). The overall hypothesis of this dissertation is that pancreatic stellate cells activate to a fibroblast phenotype that plays a significant role in the ECM and tissue stiffness of PDAC. To evaluate this hypothesis we used mouse models, isolated cultured cells, and patient tumor samples as well as clinical RNA sequencing data from PDAC patients. The following chapters will address the following three aims.