Our laboratory is involved in two major areas of focus. The first involves studying the regulation, function and disease association of the cytoskeletal intermediate filament proteins that are specifically expressed in digestive-type epithelia. These proteins are termed keratin polypeptides 8, 18, 19 and 20 (K8/K18/K19/K20). The second area of focus involves studying the stress-inducible protein heme oxygenase-1 (HO-1) as a potential therapeutic target in acute pancreatitis. This is based on our findings that compounds that induce HO-1, such as hemin, protect from injury in two models of experimental acute pancreatitis.
Our keratin-related human disease association studies address understanding the importance of K8/K18/K19 mutations in predisposition to acute and chronic liver disease, and understanding the molecular pathogenesis and significance of the hepatocyte inclusions, Mallory-Denk bodies. We approach studying keratin regulation and function in the liver, intestine and pancreas by using genetic and molecular means that include the characterization of keratin posttranslational modifications (e.g., phosphorylation and glycosylation) and keratin associated proteins such as members of the 14-3-3 family that play important roles in cell signaling.
The studies pertaining to HO-1 include assessment of its modulation in human acute pancreatitis, and understanding the mechanism of protection upon HO-1 induction which relates to unique leukocyte subset homing to the pancreas. The animal studies to date provide encouraging support for potential therapeutic and prophylactic applications to human acute pancreatitis.