The Hingorani laboratory studies the molecular and cellular origins of pancreas cancer primarily through the use of genetically engineered mouse models. Pancreas cancer is a nearly uniformly lethal disease that defies all forms of conventional chemotherapy and radiotherapy. The same factors that conspire to obscure the diagnosis of the disease in patients until very advanced stages also hinder the study of its pathogenesis. Through directed expression of key mutations in specific oncogenes and tumor suppressor genes in the mouse pancreas, we have developed models that faithfully mimic the spectrum of human PDA from its earliest preinvasive lesions to locally invasive and widely metastatic disease (for examples, see Cancer Cell 4:437-450, 2003 and Cancer Cell 7:469-483, 2005). These investigations have also helped identify unique genetic routes to pancreas cancer with distinct clinical and histopathologic features (Cancer Cell 11:229-243, 2007), and revealed unique points of vulnerability to exploit therapeutically (Science 324:1457-1461, 2009). The murine models provide rigorous platforms for preclinical studies of disease-specific detection and treatment strategies and represent key components toward achieving the comprehensive epidemiologic, detection and therapeutic aims of the Center for Accelerated Translation in Pancreas Cancer (CATPAC), directed by Dr. Hingorani.