Primary Appointment

 My Research interests are to understand the pathogenesis of pancreatic adenocarcinoma (PDAC) and the related disease chronic pancreatitis (CP) in genetically engineered mouse models. For these purposes, we perform pancreas specific gene expression and deletion utilizing the Cre-loxp technology. One of my research interests is the role of Ras activity in CP and PDAC. K-Ras mutations are frequent in both diseases. We found sufficient Ras activity in pancreatic acinar induces CP and subsequently PDAC. This suggests that elevated Ras activity through active mutations or extrinsic stimuli can be a cause of CP. Our future plan focuses on dissecting downstream signaling pathways that are critical for the inflammation and tumorigenesis. Another research focus is the roles of trypsin in CP and PDAC. Premature trypsinogen activation is believed to be the initiating event in pancreatitis. The cumulative risk of pancreatic cancer to age 70 years in patients with hereditary pancreatitis (HP), a disease casued by trypsinogen mutation, approaches 40%. We aim to study the role of trypsin in pancreatitis and develop mouse models of HP. We developed a mutant trypsinogen which is activated intracellularly. We found that intracellular trypsin caused cell death through caspase dependent and independent pathways. However, intracellular trypsin had no significant effect on the activity of NF-κB. In contrast, extracellular trypsin caused cell damage and dramatically increased NF-κB activity. These findings indicate that localization of active trypsin determines its effects on pancreatic acinar cells. Currently, we are analyzing the mouse models developed with active trypsin and mutant trypsinogen constructs.

Last updated: 9/24/2009