Mr John Murphy

Title: The role of intracellular second messenger and premature intracellular enzyme activation in the pathogenesis of acute pancreatitis

Project Start Date: January 2005

Completion Date: January 2007

Summary:

Acute Pancreatitis is a common and life-threatening disease of the pancreas, a gland at the back of the abdomen that releases enzymes into the intestine to digest food. Normally the enzymes do not become active until they enter the intestine, and are harmless. In pancreatitis the enzymes are activated prematurely, and digest the pancreas. In some patients the pancreas is so badly damaged that part or all of it dies, leading to failure of other parts of the body, with patients dying or spending many months in hospital. This disease is therefore a great burden to patients, and very costly to the National Health Service.

The two major causes are gallstones and alcohol, but how these cause acute pancreatitis is not well understood. Normal enzyme release is switched on by calcium signals inside the cells, but in acute pancreatitis, these calcium signals are faulty, with large rises in calcium levels inside the cells, leading to premature activation of the enzymes within the cells. We will study how toxic rises in calcium are produced, and how the toxic rises make enzymes active inside cells and cause cellular destruction and death. We hope that the results from this work will help to provide new targets for drugs to prevent and cure the disease, and lessen the burden of suffering that it causes.