Title: Amelie Waring Fellowship: Defining the mechanistic role of kynurenine 3-monoxygenase (KMO) inhibition in the resolution of organ dysfunction in severe acute pancreatitis
Funder: CORE

Abstract: In very broad terms what is the problem that this project is going to address?Inflammation of the pancreas, called ‘acute pancreatitis’, can range from a mild illness to a life threatening disease. Severe pancreatitis begins with inflammatory damage in the pancreas that spreads quickly around the body, leading to failure of vital organs, particularly the lungs and kidneys. There is no specific treatment that targets the disease process directly, and this is urgently needed. In those who do survive a severe attack, we know very little about the lasting effects on the body’s organs. This research will study the recovery of severe pancreatitis, investigating an exciting new pathway that has been found to reduce damage to the lungs and kidneys during the early stages of the illness and may speed up the healing process. This work could make a significant difference to those people who suffer a severe attack of acute pancreatitis, not only in the short term but will also improve understanding of the longer-term effects, as organs repair and scar, providing new insights into targeted treatments.Who is collaborating with you on this project, in what capacity and where are they based? At this stage we don’t have formal collaborations planned with other Universities for my specific project. However, the group I am joining is currently enjoying good collaborations with industry (GSK) to develop novel therapies, and is working collaboratively with Universities and Healthcare institutions at home and abroad on other projects in the field of pancreatitis and drug discovery.What will this project do and how long it will take?Using a laboratory model, I will study the inflammation biology of severe acute pancreatitis during the period when organ damage begins to resolve. Our particular focus is a metabolic pathway that seems to be damaging at high levels in patients with pancreatitis. In the laboratory, I will discover how and when blocking this pathway might be beneficial. We will also compare our laboratory findings with samples from hospital patients with acute pancreatitis to bring my project even closer to the clinic. Throughout my fellowship I will be involved in sharing our work with other scientists, healthcare professionals and patients, and will bring together all my findings into a PhD thesis and scientific papers. I am starting my project in August 2014, and expect to complete my project in 2017.What will ‘success’ look like for this project?Success for this project will be gaining a firm understanding on how acute pancreatitis starts to get better in the first few days of the disease in most patients, and whether the metabolic pathway we are studying is important to that process. What will be really exciting is if the drugs we are developing to block the pathway can help that resolution process. However, we won’t know that until we have done the experiments!


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: ORAL AND GASTROINTESTINAL