Professor Robert Sutton BA (Hons), MB, BS, DPhil, FRCS
Professor of Surgery Molecular & Clinical Cancer Medicine
- +44 (0)151 795 8024
- Work email R.Sutton@liverpool.ac.uk
- Personal Websitehttp://www.liv.ac.uk/Surgery/rsut.html
Research
Pancreatitis
Abnormal calcium signalling is a critical feature of pancreatitis:
Pancreatic acinar cells occupy the bulk of the pancreas, making and secreting digestive zymogens into the intestine to break down food for digestion and absorption. Normal signalling within pancreatic acinar cells by calcium causes these cells to secrete inactive enzymes that are activated by duodenal enterokinase, converting trypsinogen to tryspin, which triggers an activation cascade. Excessive cytosolic calcium induces premature digestive enzyme activation within acinar cells, the hallmark of acute pancreatitis. Recurrent attacks lead to the painful, debilitating condition chronic pancreatitis, which in turn confers a markedly increased risk of pancreatic carcinoma. Hereditary pancreatitis successively features all three conditions, caused by trypsinogen gene mutations that make trypsinogen more readily activated, or once activated, more resistant to degradative inactivation. We aim for a full understanding of signalling mechanisms in the pancreas and in other organs, to define the exact cellular triggers and consequences of premature digestive enzyme activation and the course of acute and chronic pancreatitis, as well as to identify and exploit novel therapeutic targets for these major human diseases.
Our discoveries:
We have discovered cytosolic calcium overload to be critical in pancreatitis. Toxins that induce pancreatitis elicit excessive calcium release from intracellular stores, inducing zymogen activation. We have identified alcohol-induced pancreatic injury by fatty acid ethyl esters, non-oxidative ethanol metabolites, which induce calcium overload via inositol trisphosphate receptors so causing mitochondrial injury, necrosis and pancreatitis. We demonstrated direct cholecystokinin stimulation of human pancreatic acinar cells, confirming human and murine parallels, so enhancing drug development. We found excessive pancreatic acinar cell reactive oxygen species promote apoptosis not necrosis, explaining negative clinical trials. We have discovered ed the efficacy of new drugs inhibiting calcium entry via Orai channels as well as drugs inhibiting formation of the mitochondrial permeability transition pore, and using preclinical testing we have demonstrated the importance of door of door to needle time. Phase II trials are currently underway testing calcium entry inhibition in acute pancreatitis. We are leading an open UK-wide phase II trial testing early administration of infliximab in acute pancreatitis, funded by the Efficacy and Mechanism Evaluation Programme (MRC/NIHR): RAPID-I: Randomised treatment of Acute Pancreatitis with Infliximab: Double- blind, placebo-controlled, multi-centre phase II trial.
Pancreatology
My further research includes optimal management of acute pancreatic necrosis; mechanisms of immune destruction of the exocrine pancreas; exocrine and endocrine pancreatic insufficiency and their management; improved selection of patients with chronic pancreatitis for surgery; and development of national and international consensus and guidelines in the optimal management of patients with acute pancreatitis, chronic pancreatitis, pancreatic exocrine insufficiency, pancreatic cancer, gastro-entero-pancreatic neuroendocrine tumours and portal hypertension.
Research Grants
Research Capability Funding Open Call
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST (UK)
June 2018 - February 2019
Cypralis Liverpool Research Collaboration in Acute Pancreatitis
INNOVATE UK (UK)
January 2017 - December 2017
Isle of Man Anti-Cancer Association donation to assist with continuing research work at the Liverpool Pancreas Biomedical Research Unit (LPBRU)
ISLE OF MAN ANTI-CANCER ASSOCIATION (ISLE OF MAN)
May 2015 - May 2024
NIHR Senior Investigator Award
DEPARTMENT OF HEALTH & SOCIAL CARE (UK)
April 2016 - March 2024
Liverpool Health Genomics Laboratory
LIVERPOOL HEALTH PARTNERS (UK)
March 2015 - February 2018
The role of intracellular second messengers and premature intracellular enzyme activation in the pathogenesis of acute pancreatitis.
DIGESTIVE DISORDERS FOUNDATION
February 2006 - January 2007
The role of calcium and apoptosis in pancreatic oxidant injury: Intracellular two-photon imaging real time studies.
MEDICAL RESEARCH COUNCIL
March 2004 - August 2007
Role of NF-kappaB signalling in acute experimental pancreatitis
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST (UK)
March 2014 - February 2015
Liverpool Imaging Partnership: Molecular physiology and drug response
MEDICAL RESEARCH COUNCIL
February 2013 - February 2017
Application of high throughput genomic science technologies to NIHR research programmes
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST (UK)
September 2010 - September 2013
Bench fees in support of students within the Pancreas Biomedical Research Unit
WEST CHINA SCHOOL OF MEDICINE SICHUAN UNIVERSITY (CHINA) 🚩
April 2012 - October 2015
Visiting Chinese academic to Pancreas Biomedical Research Unit
CONSULATE GENERAL OF PEOPLE'S REPUBLIC OF CHINA IN MANCHESTER
January 2012 - December 2013
Role of intracellular calcium in the pathogenesis of acute pancreatitis.
MEDICAL RESEARCH COUNCIL
July 2002 - June 2005
Amelie Wareing Research Fellowship for R Mukherjee
DIGESTIVE DISORDERS FOUNDATION
August 2007 - July 2010
An open randomised comparison of the clinical effectiveness and costs of protocol driven opioid analgesia, celiac plexus block, or thoracoscopic splanchnicectomey for pain relief in patients with abdominal malignancy.
DEPARTMENT OF HEALTH & SOCIAL CARE (UK)
February 2001 - January 2004
Cellular biology of the gastrointestinal tract and pancreas in health and disease.
MEDICAL RESEARCH COUNCIL
January 2005 - December 2009
Liver research.
LIVER CANCER APPEAL (UK)
August 2000 - October 2003
Pancreatic acinar cellular mechanisms of injury that determine the severity of acute pancreatitis in rodent, porcine and human pancreas.
ROYAL COLLEGE OF SURGEONS OF ENGLAND(UK)
February 2007 - January 2008
Ca2+ Signalling, Organelle Dysfunction and Pancreatis
MEDICAL RESEARCH COUNCIL
November 2008 - October 2011
Calcium-dependent enzyme activation in acute pancreatitis.
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST (UK)
February 2006 - October 2008
Cyclophilin D Drug Discovery Project
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST (UK)
August 2012 - July 2015
Drug discovery for acute pancreatitis
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST (UK)
April 2012 - March 2013
Interaction of endocytic vacuoles with cellular organelles as a trigger for the cell damage in acute pancreatitis.
MEDICAL RESEARCH COUNCIL
February 2013 - April 2016