Mr Alastair Hayes
Title: Defining the mechanistic role of kynurenine 3-monooxygenase (KMO) inhibition in the resolution of organ dysfunction in severe acute pancreatitis
Project Start Date: August 2014
Completion Date: August 2017
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.
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.
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.
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!
As a trainee surgeon, I have become deeply committed to studying disease of the pancreas. Most of the sick patients we look after in surgery departments have a clear treatment, usually in the form of an operation or a procedure to reverse the disease process. Severe pancreatitis has no disease specific treatment and challenges our understanding as doctors. For example, why should some people who are relatively young die from pancreatitis when others have only a mild attack? How does the inflammation process stop itself, given that not all patients with the severe form of pancreatitis die? And what cellular mechanisms can be switched off or on to help these patients? Clearly this is a very interesting area and in the University of Edinburgh there is a great deal of expertise in inflammation biology to best understand the processes involved.
This project focuses on pancreatitis patients who represent a large number of emergency hospital admissions each year, and result in lots of unplanned days spent in intensive care beds up and down the country. Not only does acute pancreatitis have a drastic impact upon many patients and their families, it also has a massive financial burden. I will be studying the healing processes during acute pancreatitis and the biology involved in reducing the severest form of the disease. The focus will be upon potential new treatments that reduce the damage to other organs around the body, with the hope of limiting the impact of pancreatitis.
I am pursuing a career in academic liver and pancreas surgery and aim to combine a commitment to up-to-date clinical practice with cutting edge translational basic science research. This Amelie Waring Fellowship will provide training that will have life-long application for laboratory and clinical research by way of providing the skills with which to be able to develop translational-based research questions that benefit patients. The focus of this research is on the resolution of multi-organ failure in pancreatitis, an area which is very much in need of investigation but requires collaboration between experienced clinicians, scientists and pharmaceutical industry, in order for high quality and high impact research to be produced. During this fellowship, as we develop the research, I will be able to see the next step in improving care for patients with pancreatitis.
The fantastic support from Core through the Amelie Waring Fellowship has helped me realise my aspiration to dedicate 3 years to researching an exciting area related to acute pancreatitis where I can contribute to a team which is focussed on developing new medicines. The team I am part of is on the cusp of moving our discoveries into clinical trials, where the effects of kynurenine pathway inhibitor drugs can be safely assessed in patients.Mr Alastair Hayes