I guide the residents, PhD and MD students in investigating the molecular pathogenesis of pancreatitis and pancreas regeneration by using various genetically modified mouse models. We also study the molecular mechanisms of chemoresistance in pancreatic cancers, as well as sphingolipid metabolism in autoimmune disease. Proteins of the Reg/PAP family are secreted in abundance by pancreatic acinar cells in the inflamed and regenerating pancreas. Using Reg1 KO mice, they have identified Reg1 as a physiological activator of stellate cells required for normal pancreas regeneration. In addition, using PAP1 KO and PAP2 KO mice, they have found that PAP1 and PAP2 proteins have differential anti-inflammatory and tissue protective functions in pancreatitis. These functions are associated with PAP1 and PAP2's different roles in NFkB activation in acinar cells. Given the importance of stellate cell and NFkB in the pathogenesis of pancreatitis and pancreatic cancers, their results reveal potential roles of targeting Reg/PAP proteins for the development of new therapeutic approaches. PI3K/Akt and ERK signaling pathways have been found to play key roles in the survival and chemotherapy resistance of pancreatic cancer cells with undefined upstream regulators and downstream effectors. They have found that PI3K/Akt and ERK-regulated p21 protein levels and cellular locations affect gemcitabine resistance in pancreatic cancer cells. Currently they are investigating the role of Reg/PAP-mediated activation of PI3K/Akt in regulation of chemoresistance in pancreatic cancer cells. In collaboration with other researchers and clinicians in the Departments of Cell Biology and Medicine at Downstate, they are also exploring the novel functions of sphingolipid synthesizing enzymes in the regulation of cell polarity and the pathogenesis of autoimmunity in mice and patients.