Pancreatic Research Group

WHO ARE WE

The research interests of the Pancreatic Research Group are predominantly related to diseases of the exocrine pancreas including acute and chronic pancreatitis (inflammation of the gland) and pancreatic cancer. The Group is an internationally acknowledged leader in the field of pathogenesis of alcohol-induced pancreatitis.

Professor Minoti Apte was the first in the world to isolate and characterise pancreatic stellate cells (PSCs), a development that unlocked the key to a largely undeveloped area of research in pancreatology, namely the elucidation of the molecular mechanisms of pancreatic fibrogenesis.

The Group’s seminal studies regarding the biology of pancreatic stellate cells in health and on the role of these cells in pancreatitis and pancreatic cancer have placed it firmly at the forefront of world pancreatology.

WHAT WE DO

The Group’s research involves both in vivo (animal models and human studies) and in vitro approaches. Currently the following specific areas are under investigation:

• Molecular mechanisms responsible for the initiation, progression and reversion of alcohol-induced acute and chronic pancreatic injury
• Characterising the interaction between pancreatic stellate cells and pancreatic cancer cells that facilitates cancer progression
• Possible therapeutic interventions targeting PSC-cancer interactions to inhibit pancreatic cancer growth and metastasis
• Role of heat shock proteins in pancreatic stellate cell function with particular reference to the biology of PSCs in inflammation and carcinogenesis
• Elucidating the mechanisms of chemoresistance in pancreatic cancer with a particular focus on cancer desmoplasia

FUNDING

The Group has received continuous funding from the NH&MRC since 1987. In addition it has attracted funding from the ARC (Discovery project), NSW Cancer Council, Ramaciotti Foundations, Alcohol Health and Research Grants Scheme, Cancer Institute NSW and Cure Cancer Australia as well as from a commercial company.

MEDIA HIGHLIGHTS

Recent publication in American Journal of Pathology (Z Xu, A Vonlaufen, P Phillips, E Fiala-Beer, X Zhang, L Yang, A Biankin, D Goldstein, RC Pirola, JS Wilson, MV Apte. Role of pancreatic stellate cells in pancreatic cancer metastasis. American Journal of Pathology, 177:2585-96, 2010) highlighted as News Article (www.unsw.edu.au/news/pad/articles/2010/oct/Pancreatic.html).

Dr Phoebe Phillips featured as a talented early career researcher on Cure Cancer Australia website (www.cure.org.au)

MAJOR RESEARCHERS

Prof Minoti Apte	Senior Investigator	m.apte@unsw.edu.au
Prof Jeremy Wilson	Investigator
A/Prof Ron Pirola	Investigator
Dr Phoebe Phillips	Investigator	p.phillips@unsw.edu.au

FURTHER INFORMATION

Other Team Members:
Eva Fiala-Beer (Research Assistant)
Janet Youkhana (Research Assistant)
Jie Liu (Research Assistant)
Zhihong Xu (PhD Student)
Susan Yang (Masters Student)

LINKS

Australasian Pancreatic Club (www.pancreas.org.au) : Professors Apte, Pirola and Wilson are Founding Members and Past Presidents of the Australasian Pancreatic Club (APC), the only one of its kind in Australia, that serves as a forum for clinicians and scientists with an interest in clinical and basic research into diseases of the exocrine pancreas. Dr Phillips is currently the Honorary Secretary of the APC.

New South Wales Pancreatic Cancer Network (NSWPCN; www.pancreaticcancer.net.au) : Professor Apte was a Chief Investigator on Strategic Research Partnership Grant from the NSW Cancer Council, which was awarded to set up the first comprehensive tumour bank and clinical data repository for pancreatic cancer in the State.

SELECTED 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.