Pancreatic Research Group
Research Interests
These are related to the molecular mechanisms of diseases of the exocrine pancreas, in particular pancreatitis (inflammation of the pancreas) and pancreatic cancer. Alcoholic pancreatitis is a common complication of alcohol abuse in Western countries. The Pancreatic Research Group is acknowledged as a leading group in the world with respect tor research into the pathways by which alcohol causes pancreatic damage leading to necrosis of pancreatic acinar cells, inflammation of the gland and, in chronic disease, fibrosis of the pancreas. The Group was the first in the world to isolate and characterise pancreatic stellate cells, now established as key effector cells in pancreatic fibrogenesis. Work over recent years has consolidated the position of the Group at the cutting edge of international research in the field of pancreatic fibrosis.
Another major area of interest is the pathogenesis of pancreatic cancer. Pancreatic cancer has an extremely poor prognosis with the majority of patients succumbing to the disease within months of diagnosis. There is an urgent need for improved understanding of the molecular mechanisms responsible for the early local and distant spread (a characteristic feature) of pancreatic cancer. To this end, the Group is currently examining the role of epithelial-stromal interactions in local invasion and distant metastasis of pancreatic cancer.
The Group has received continuous competitive grant support from the National Health and Medical Research Council of Australia since 1987 and has also received support from the Department of Veterans’ Affairs, the Clive and Vera Ramaciotti Foundation, the Australian Brewers Association, the Gastroenterological Society of Australia and the Health Research Foundation Sydney South West. The international recognition of the Group’s work is reflected in the invitations that A/Prof Apte and Professor Wilson have received to speak at international meetings held in the United States (American Gastroenterological Association, American Pancreatic Association and the National Institute on Alcohol Abuse and Alcoholism; NIAAA), Germany (the European Pancreatic Club), the Czech Republic (the European Society for Biochemical Research on Alcoholism; ESBRA), the United Kingdom (the Pancreatic Society of Great Britain and Ireland), India (Indian Pancreas Club), Mexico (Mexican Gastroenterological Association) and Japan (Japan Pancreas Society).
Research Projects
Alcoholic Pancreatitis
This project examines the pathogenesis pancreatic fibrosis, a characteristic feature of alcohol-induced chronic pancreatitis. The findings have the potential to delineate the early events in alcohol-related fibrogenesis in the pancreas and to suggest new therapeutic approaches (inhibitors of ethanol metabolism, inhibition of specific signalling pathways, neutralising antibodies to cytokines) to prevent or slow the progression of pancreatic fibrosis in heavy drinkers. The comprehensive characterisation of alcohol-related PSC activation may also have implications for stellate cell studies in extrapancreatic sites, particularly in the liver (another major target organ for alcohol-induced injury).
Pancreatic Cancer
This project has the potential to yield novel findings in an area of pancreatic tumour pathobiology that has received little attention to date. Data from these studies will help to define the role of the stroma in the pathogenesis of pancreatic cancer and to understand the processes by which subversion of host cells by tumour cells could facilitate local and distant invasion. The project also has the potential to identify molecular mechanisms that could be therapeutically targeted in order to retard and/or prevent the progression of pancreatic cancer. It is likely that our findings will also be relevant to other cancers involving subversion of the host system such as scirrhous breast carcinoma, biliary carcinoma and liver metastases of carcinomas.
Researchers
Recent Publications
Apte MV, Phillips PA, Fahmy RA, Darby SJ, Rodgers SC, McCaughan GW, Korsten MA,
Pirola RC, Naidoo D,
Wilson JS. Does alcohol directly stimulate pancreatic fibrogenesis? Studies with rat pancreatic stellate cells.
Gastroenterology 118:780-794, 2000. [with cover illustration]
Mews P, Phillips P, Fahmy R,
Pirola R, Korsten M,
Wilson J,
Apte M. Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis.
Gut, 50:535-541, 2002.
Apte M. Oxidative stress : does it initiate hepatic stellate cell activation or only perpetuate the process? (Editorial)
Journal of Gastroenterology and Hepatology, 17:1045-1048, 2002.
Apte M,
Wilson J. Invited commentary on "Pancreatic stellate cells contribute to regeneration early after acute necrotising pancreatitis in humans" by Zimmermann et al (Gut2002;51:574-578).
Apte MV,
Wilson JS. “Experimental models of pancreatic fibrogenesis and the role of stellate cells” in
Chronic Pancreatitis – Novel Concepts in Biology and Therapy, Buchler M, Friess H, Uhl W, Malfertheiner P (eds), Blackwell Science, pp 113-133, 2002.
Phillips P, Wu M-J, Doherty E, Kumar RK, McCarroll J, Park S,
Pirola R,
Wilson J,
Apte M. Cell migration : A novel aspect of pancreatic stellate cell biology.
Gut 52:677-82, 2003.
McCarroll, J, Phillips P, Park S, Doherty E,
Pirola R,
Wilson J,
Apte M. Pancreatic stellate cell activation by ethanol and acetaldehyde – is it mediated by the mitogen-activated protein kinase (MAPK) signalling pathway?
Pancreas 27:150-160, 2003.
Phillips PA, McCarroll JA, Park S, Wu M-J, Korsten MA,
Pirola RC,
Wilson JS,
Apte MV. Pancreatic stellate cells secrete matrix metalloproteinases – implications for extracellular matrix turnover.
Gut, 52:275-282, 2003.
Apte MV,
Wilson JS. “What’s new in pancreatic stellate cell biology?” In
Pancreatic Disease, Johnson C, Imrie C (eds), Springer-Verlag 17:201-225, 2003.
Apte MV,
Wilson JS. Chronic pancreatitis : How and why is fibrosis initiated? In
Controversies in Pancreatology, Permert J, Herrington M, Adrian TE (eds), Crlsson Communications, pp. 80-92, 2003.
Apte MV,
Wilson JS. Stellate cell activation in alcoholic pancreatitis.
Pancreas 27:316-320, 2003.
Wilson JS,
Apte MV. Role of alcohol metabolism in alcoholic pancreatitis.
Pancreas 27:311-315, 2003.
Apte MV,
Wilson JS. Alcohol-induced pancreatic injury.
Best Practice Research and Clinical Gastroenterology 17:593-612, 2003.
McCarroll JA, Phillips PA, Kumar RK, Park S,
Pirola RC,
Wilson JS,
Apte MV. (2004) Pancreatic stellate cell migration: role of the phosphatidylinositol 3-kinase (PI3-kinase) pathway.
Biochemical Pharmacology, 67:1215-1225.
Haber PS,
Apte MV, Moran C, Applegate TL,
Pirola RC, Korsten MA, McCaughan GW,
Wilson JS. Non-oxidative metabolism of ethanol by rat pancreatic acini.
Pancreatology, 4:82-89, 2004.
Apte MV, Park S, Phillips PA, Santucci N, Goldstein D, Kumar RK, Ramm G, Buchler M, Friess H, McCarroll JA, Keogh G, Merrett N,
Pirola RC,
Wilson JS. Role of epithelial-stromal interactions in the pathogenesis of pancreatic cancer.
Pancreas, 29:179-187, 2004.
Goldstein D,
Apte M, Carroll S, Keogh G. Modern management of pancreatic cancer.
Internal Medicine Journal 34:475-481, 2004.
Apte MV,
Wilson JS. Experimental models of pancreatic fibrogenesis.
FALK Symposium Proceedings, in press, October 2004
Apte MV,
Wilson JS. Pancreatitis in the older adult.
Geriatrics and Aging 7:27-35, 2004.
Apte MV,
Wilson JS. Mechanisms of pancreatic fibrosis.
Digestive Diseases 22:273-279, 2004.
Apte MV,
Pirola RC,
Wilson JS. Where there’s smoke there’s not necessarily fire.
Gut, 54:446-7, 2005.
Apte MV,
Wilson JS. The importance of keeping in touch: regulation of cell-cell contact in the exocrine pancreas.
Gut, in press, 2005.
Apte MV,
Wilson JS. Molecular mechanisms of alcoholic pancreatitis in “
Alcohol and the Gastrointestinal Tract” Eds Manfred V. Singer, David Brenner, in press.
McCarroll J, Phillips PA, Santucci N,
Pirola RC,
Wilson JS,
Apte MV. Vitamin A inhibits pancreatic stellate cell activation: implications for treatment of pancreatic fibrosis.
Gut, 2005 Jul 25; [Epub ahead of print] ; PMID: 16043492.