Dr. Samuel's research interests focus on acute pancreatitis. In serious cases, acute inflammation originating in the pancreas spreads systemically and manifests with multiple organ failure associated with a high risk of death. In spite of the serious nature of acute pancreatitis an inadequate understanding of the pathogenesis involved is hampering effective treatment. Morbidity and mortality associated with acute pancreatitis are, in large part, related to the overproduction of cytokines by the pancreas; hence, an understanding of the mechanism that underlies pancreatic cytokine production is of paramount importance both in the elucidation of early events in disease pathogenesis and in the design of new therapies. Dr. Samuel?s group hypothesizes that, when the duct is obstructed, neuro-hormonal pathways (CCK-A receptor and cholinergic receptor), induces pancreatic hyperstimulation due to the exclusion of bile-pancreatic juice, and that this in turn induce undue pancreatic acinar cell stress. As a consequence, pro-inflammatory signal transduction pathways within the acinar-cell induce the production of inflammatory mediators (cytokines, chemokines, free radicals) that exacerbate acute pancreatitis. In this regard, an investigation of the role of acinar cell signaling pathways such as the stress kinase (p38, JNK, ERK) pathway or the Akt/NFkB pathway is of special interest. The role of pancreatic hyperstimulation via G-protein coupled receptors (CCK receptor and cholinergic receptor) and their regulation by the novel RGS (regulation of G-protein signaling) proteins is also under investigation. Studies use a number of genetic approaches to investigate these areas, including transgenic/knockout mice and recombinant adenoviral vectors. The group's long-term goal is to elucidate the mechanisms underlying the pathogenesis of acute pancreatitis, with a view to ultimately implementing new treatment modalities including gene therapy.
Selected Publications:
Samuel, I., Tephly, L., Williard, D.E., and Carter, A.B. 2008. Enteral exclusion increases map kinase activation and cytokine production in a model of gallstone pancreatitis. Pancreatology 8:6-14.
Samuel, I. 2008. Bile and pancreatic juice exclusion activates acinar stress kinases and exacerbates gallstone pancreatitis. Surgery 143:434-440.
Samuel, I., Zaheer, A., and Fisher, R.A. 2006. In vitro evidence for role of ERK, p38, and JNK in exocrine pancreatic cytokine production. J Gastrointest Surg 10:1376-1383.
Samuel, I., Yorek, M.A., Zaheer, A., and Fisher, R.A. 2006. Bile-pancreatic juice exclusion promotes Akt/NF-kappaB activation and chemokine production in ligation-induced acute pancreatitis. J Gastrointest Surg 10:950-959.
