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Pancreatic Stellate Cells in Chronic Pancreatitis

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Pancreatic Stellate Cells in Chronic Pancreatitis 0 Pancreatic Stellate Cells in Chronic Pancreatitis Lu Yang September 2011 Thesis submitted for a degree of Master by Research Faculty of Medicine The University of New South Wales, Sydney, NSW, Australia i Certificate of Originality ‘I hereby declare that this submission is my own work and to the best of my knowledge it contains no materials previously published or written by another person, nor material which to a substantial extent has been accepted for the award of any other degree or diploma at UNSW or any other educational institution, except where due acknowledgement is made in the thesis. Any contribution made to the research by others, with whom I have worked at UNSW or elsewhere, is explicitly acknowledged in the thesis. I also declare that the intellectual content of this thesis is the product of my own work, except to the extent that assistance from others in the project’s design and conception or in style, presentation and linguistic expression is acknowledged.’ Signed……………………………………………………………… ii Acknowledgements I would like to express my gratitude to my masters’ supervisors Professor Minoti Apte, Dr Phoebe Phillips and Professor Jeremy Wilson, for the opportunity to undertake a master project in the field of alcoholic pancreatitis and for their assistance, guidance and support throughout my candidature. Professor Minoti Apte is not only a scientist of superior quality but also a wonderful person who was always positive, patient and possesses great leadership qualities. Dr Phoebe Phillips has been a constant source of inspiration and provided me with precious intellectual and technical advice. Professor Jeremy Wilson, Head of South Western Sydney Clinical School, despite his many commitments, provided invaluable assistance, encourage, advice and support throughout my studies and during the preparation of this thesis. I thank all past and present research staff of the Pancreatic Research Group (A/Professor Ron Pirola, Zhihong Xu, Xuguo Zhang, Eva Fiala-Beer, Jie Liu, Janet Youkhana and Narada Kiriella) for their support and their help with the isolation of pancreatic stellate cells. Thank you to Dr Alain Vonlaufen for his assistance and advice during my masters candidate and his patience in training me with several lab techniques. I would like to thank my parents for all their understanding, encouragement and patience through out my studies. Finally, I would like to offer my husband Jin a special thankyou for his love, understanding and unconditional support during my studies. iii Publications ___________________________________________________________________ Publications in peer reviewed journals 1. Phillips PA, Yang L, Shulkes A, Vonlaufen A, Poljak A, Bustamante S, Warren A, Xu Z, Guilhaus M, Pirola R, Apte MV, Wilson JS. Pancreatic Stellate Cells Synthesize and Secrete Acetylcholine: A potential role in exocrine pancreatic secretion, Proc Natl Acad Sci U S A. 2010 Oct 5; 107(40):17397-402. 2. Vonlaufen A, Phillips PA, Yang L, Xu Z, Fiala-Beer E, Zhang X, Pirola RC, Wilson JS, Apte MV. Isolation of quiescent normal human pancreatic stellate cells (NhPSCs): a promising in vitro tool for studies of hPSC biology, Pancreatology. 2010; 10(4):434-43. 3. Xu Z, Vonlaufen A, Phillips PA, Fiala-Beer E, Zhang X, Yang L, Biankin AV, Goldstein D, Pirola RC, Wilson JS, Apte MV. Role of pancreatic stellate cells in pancreatic cancer metastasis, Am J Pathol. 2010 Nov; 177(5):2585-96. 4. Vonlaufen A, Phillips PA, Xu Z, Zhang X, Yang L, Pirola RC, Wilson JS, Apte MV. Withdrawal of alcohol promotes regression while continued alcohol intake promotes persistence of LPS-induced pancreatic injury in alcohol-fed rats, Gut. 2011 Feb; 60(2):238-46. iv Abstracts 1. Yang L*, Phillips PA*, Vonlaufen A, Kaplan W, Cowley M, Pirola R, Wilson JS and Apte MV. Collagen-I Increases the Expression of Transgelin and Lumican (regulators of cell migration) by Activated Pancreatic Stellate Cells. *These authors contributed equally to the study. Awarded Best Poster Prize at the the Joint Conference of the International Association of Pancreatology and the Indian Pancreas Club, Cochin, 2011 2. Fiala-Beer E, Xu Z, Phillips PA, Yang L, Goldstein D, Pirola R, Wilson JS and Apte M. Role of pancreatic stellate cells in pancreatic cancer: the urokinase plasminogen activator system. Role of pancreatic stellate cells in pancreatic cancer: the urokinase plasminogen activator system. Oral presentation in the plenary session at the Joint Conference of the International Association of Pancreatology and the Indian Pancreas Club, Cochin, 2011. 3. Yang L*, Phillips PA*, Vonlaufen A, Kaplan W, Cowley M, Pirola R, Wilson JS and Apte MV. Collagen-I Increases the Expression of Transgelin and Lumican (regulators of cell migration) by Activated Pancreatic Stellate Cells. *These authors contributed equally to the study. Awarded in the Poster of Merit competition and won postgraduate student travel award in the annual scientific meeting of Australia Gastroenterology Week Oct. 2010 4. Yang L*, Phillips PA*, Vonlaufen A, Kaplan W, Cowley M, Pirola R, Wilson JS and Apte MV. Collagen-I Increases the Expression of Transgelin and Lumican (regulators of cell migration) by Activated Pancreatic Stellate Cells. *These authors contributed equally to the study. Oral presentation at 5th Australian Health and Medical Research Congress (AH&MRC) Nov.2010 5. Yang L*, Phillips PA*, Vonlaufen A, Kaplan W, Cowley M, Pirola R, Wilson JS, and Apte MV. *These authors contributed equally to the study. Collagen-1 increases the expression of transgelin and lumican (regulators of cell migration) by activated pancreatic stellate cells. Pancreas, 2010; 39(8):p1358. Poster presentation at the annual American Pancreatic Association meeting, 2010. 6. Yang L*, Phillips PA*, Vonlaufen A, Kaplan W, Cowley M, Pirola R, Wilson JS and Apte MV. Collagen-I Increases the Expression of Transgelin and Lumican (regulators of cell migration) by Activated Pancreatic Stellate Cells. v *These authors contributed equally to the study. Poster presentation at European Pancreatic Club Meeting Jun, Sweden, 2010 7. Yang L*, Phillips PA*, Vonlaufen A, Kaplan W, Cowley M, Pirola R, Wilson JS, and Apte MV. *These authors contributed equally to the study. Collagen-1 increases the expression of transgelin and lumican (regulators of cell migration) by activated pancreatic stellate cells. Oral presentation at the annual Ingham’s Research Showcase, 2010 8. Fiala-Beer E, Xu Z, Phillips PA, Yang L, Goldstein D, Pirola R, Wilson JS and Apte M. Role of pancreatic stellate cells in pancreatic cancer: the urokinase plasminogen activator system. Oral presentation at the annual Australasian Pancreatic Club meeting, 2010. 9. Xu Z, Phillips PA, Vonlaufen A, Fiala-beer E, Yang L, Zhang X, Biankin AV, Goldstein D, Pirola RC, Wilson JS, Apte MV. Normal pancreatic stellate cells facilitate pancreatic cancer progression, exhibit transendothelial migration and accompany cancer cells to distant metastatic sites. Oral presentation at the annual Ingham’s Research Showcase, 2010. 10. Fiala-Beer E, Xu Z, Phillips PA, Yang L, Goldstein D, Pirola R, Wilson JS and Apte M. Role of pancreatic stellate cells in pancreatic cancer: the urokinase plasminogen activator system. Oral presentation at the annual Ingham’s Research Showcase, 2010. 11. Yang L*, Phillips PA*, Vonlaufen A, Kaplan W, Cowley M, Pirola R, Wilson JS and Apte MV. Gene expression profiling of rat pancreatic stellate cells. *These authors contributed equally to the study. Poster presentation at American Pancreatic Association and Japan Pancreas Society, November 2009, Hawaii, USA. 12. Yang L*, Phillips PA*, Vonlaufen A, Kaplan W, Cowley M, Pirola R, Wilson JS and Apte MV. Gene expression profiling of rat pancreatic stellate cells. *These authors contributed equally to the study. Oral presentation at Australia Pancreatic Club, August 2009, Australia. 13. Yang L, Phillips PA, Vonlaufen A, Xu Z, Zhang X, Fiala-Beer E, Pirola RC, Wilson JS. Apte MV. Alcohol and cytokines stimulate pancreatic stellate cell activation. Poster presentation at 4th Australian Health & Medical Research vi Congress, 16-21 November 2008, Brisbane Convention & Exhibition Centre, Queensland, Australia. Won Travel Award. 14. Phillips PA, Yang L, Poljak A, Bustamante S, Shulkes A, Vonlaufen A, Xu Z, Guilhaus M, Pirola R, Apte MV, J. Wilson. Pancreatic stellate cells synthesise and secret acetylcholine: a potential role in enzyme secretion. Oral presentation (P.A. Phillips) European Pancreatic Club Meeting in Szeged July 2009 15. Phillips PA, Yang L, Vonlaufen A, Xu Z, Biankin A, Goldstein D, Pirola R, Wilson JS, Apte MV. Heat shock proteins are induced during pancreatic stellate cell activation in pancreatic cancer. European Pancreatic Club Meeting in Szeged July 2009 16. Phillips PA, Chow E, Kaplan W, Cowley M, Vonlaufen A, Yang L, Xu Z, Biankin A, Goldstein D, Pirola R, Wilson JS, Apte MV. Gene expression profiling of human pancreatic stellate cells and their roles in pancreatic cancer progression. European Pancreatic Club Meeting in Szeged July 2009 17. Phillips PA, Yang L, Vonlaufen A, Xu Z, Biankin A, Goldstein D, Pirola R, Wilson JS and Apte MV. Heat shock proteins are induced during pancreatic stellate cell activation in pancreatic cancer. Poster presentation at American Association for Cancer Research Annual Meeting in Denver, Apr. 2009 18. Phillips PA, Chow E, Vonlaufen A, Xu Z, Yang L, Biankin A, Goldstein D, Pirola R, Wilson JS, and Apte MV. Gene Expression Profiling of Human Pancreatic Stellate Cells and their Roles in Pancreatic Cancer Progression. Poster presentation at American Association for Cancer Research Annual Meeting in Denver, Apr. 2009 19. Phillips PA, Yang L, Vonlaufen A, Xu Z, Pirola R, Wilson JS and Apte MV. Heat shock proteins are differentially regulated during pancreatic stellate cell activation. Oral presentation (Phillips PA) at the annual meeting of American Pancreatic Association, 6-7 November 2008, Chicago IL, USA. (Pancreas, November 2008, Volume 37, Number 4, Page 459-505.) 20. Phillips PA, Yang L, Vonlaufen A, Xu Z, Pirola R, Wilson JSS and Apte MV. Heat shock proteins are differentially regulated during pancreatic stellate cell activation.
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