Basic Research > Cancer Initiation and Progression > Professor Andrea Varro

	Two-way interactions between epithelial cells and mesenchymal cells are an important determinant of normal mucosal organisation and occur during development, wound healing and in the progression to cancer. These interactions are, for example, likely to be important in determining the niche occupied by the stem cell and the transit amplifier cells, and dysfunction of this system is likely to be a contributor to the process by which epithelial tumours arise on a background of chronic tissue injury or inflammation. The mechanisms that redefine the microenvironment are still largely unknown and may include altered expression of growth factors, cytokines, extracellular proteases and protease inhibitors. Activated fibroblasts, myofibroblasts, are considered to be a key mesenchymal cell type because they produce a number of epithelial growth factors and they expand in chronic inflammation and cancer.
There is increased interest of the role of the microenvironment in carcinogenesis in several organs and a key role is suggested for activated fibroblasts in both in cancer initiation and metastasis. Research in my group is directed to understand the role of myofibroblast in gastric and oesophageal cancer progression and to exploit our findings for both diagnostic and therapeutic purposes.

Education and qualifications

1985: PhD, University of Budapest, Hungary.

1976: MBChB (Summa cum Laude), Szentgyorgyi University Medical School, Szeged, Hungary.

Appointments

2007: Honorary appointment , Royal Liverpool University Hospital.

2001: Professor, Department of Physiology, University of Liverpool.

2000: Visiting professor of Medicine,

1997-2001: Reader, Department of Physiology, University of Liverpool.

1995-1997: Senior Lecturer, Department of Physiology, University of Liverpool.

1993-1995: Lecturer, Department of Physiology, University of Liverpool.

1984-1993: Senior Research Assistant, Department of Physiology, University of Liverpool.

1983-1984: Lecturer, First Department of Biochemistry, Semmelweiss University Medical School, Budapest, Hungary.

1982: Honorary Research Fellow, Department of Physiology, University of Liverpool.

1981-1983: Hungarian Academy of Sciences Research Fellow, First Department of Biochemistry, Semmelweiss University Medical School, Budapest, Hungary.

1978-1981: Senior Research Fellow, First Department of Biochemistry, Semmelweiss University Medical School, Budapest, Hungary.

1976-1978: Research Fellow, First Department of Biochemistry, Semmelweiss University Medical School, Budapest, Hungary.

Honours and awards

2009: Keynote speaker, US National Institute of Cancer, workshop on Tumour microenvironment, Bethesda, April

2007: Invited contributor, to “Biology of Gastric Cancer” (editor T Wang; Raven Press, New York).

2007: Invited external advisor (consultancy), Syntaxin Ltd on Therapeutic drug development for gastrin related diseases.

2007: Keynote speaker, international symposium A Century of Advances in Neuroendocrine Tumor Disease, Montreux, April,
2007, and invited contributor to the conference proceedings book.

2006: Personal profile chosen as their main example of a woman holding a professorial position or directorship, Association of Medical Research Charities, Women in Science.

2006: Invited project contributor , U54 Tumor Microenvironment Network, NIH, USA.

2006: Elected Honorary Member, Hungarian Gastroenterological Society, and Hetanyi Geza medallist.

1981: Hungarian Academy of Sciences Career Development Award.

Gonda TA, Varro A, Wang TC, Tycko B. (2010) Molecular biology of cancer-associated fibroblasts: can these cells be targeted in anti-cancer therapy? Semin Cell Dev Biol.21:2-10.

Almeida-Vega, S., Catlow, K., Kenny, S., Dimaline, R., Varro, A. (2009) Gastrin activates paracrine networks leading to induction of PAI-2 via MAZ and ASC-1. Am. J. Physiol., 296: G414-23.

Kenny,S., Duval,C., Sammut,S.J., Steele,I., Pritchard,D.M., Atherton,J.C., Argent,R.H., Dimaline,R., Dockray,G.J., Varro,A. (2008) Increased expression of the urokinase plasminogen activator system by Helicobacter pylori in gastric epithelial cells. Am. J. Physiol., 295: G431-89.

Jiang, L., Gonda T.A., Gamble, M.V., Salas, M., Seshan, V., Tu, S., Twaddell, W.S., Hegyi, P., Lazar, G., Steele, I., Varro, A., Wang, T.C., Tycko, B. (2008) Global hypomethylation of genomic DNA in cancer-associated myofibroblasts. Cancer Research, 68: 9900-8.

Varro A, Kenny S, Hemers E, McCaig C, Przemeck S, Wang TC, Bodger K and Pritchard DM (2007) Increased gastric expression of MMP-7 in hypergastrinemia and significance for epithelial-mesenchymal signaling. Am J Physiol Gastrointest Liver Physiol. 292:G1133-40.

Bodger K, Ahmed S, Michael A, Khan AL, Pazmany L, Pritchard DM, Dimaline R, Dockray GJ, Varro A. (2007) Altered gastric corpus expression of tissue inhibitors of metalloproteinases in human and murine Helicobacter infection. J. Clin. Pathol., 61: 72-78.

Steele I, Dimaline R, Pritchard DM, Peek R, Wang TC, Dockray GJ, Varro A. (2007) Helicobacter and gastrin stimulate Reg1 expression in gastric epithelial cells through distinct promoter. Am. J. Physiol., 293:G347-54.

McCaig C, Duval C, Hemers E, Steele I, Pritchard DM, Przemeck S, Dimaline R, Ahmed S, Bodger K, Kerrigan D, Wang TC, Dockray GJ and Varro A (2006) The role of matrix metalloproteinase (MMP)-7 in redefining the gastric microenvironment in response to Helicobacter pylori. Gastroenterology 130:1754-63.

Hemers E, Duval C, McCaig C, Handley M, Dockray GJ, Varro A. (2005) Insulin-like growth factor binding protein-5 is a target of matrix metalloproteinase-7: implications for epithelial-mesenchymal signalling. Cancer Res., 65:7363-7369.

Varro,A., Noble, P-J. M., Pritchard, D.M., Kennedy,S., Hart, C.A., Dimaline,R., Dockray,G.J. (2004) Helicobacter pylori induces plasminogen activator inhibitor 2 (PAI-2) in gastric epithelial cells through NF-kB and RhoA: implications for invasion and apoptosis. Cancer Res., 64: 1695-1702

Wroblewski, L.E., Noble,P-J-.M., Pagliocca,A., Pritchard,D.M., Hart,C.A., Campbell,F., Dodson,A.R., Dockray,G.J. Varro,A. (2003) Stimulation of matrix metalloproteinase-7 (matrilysin) by Helicobacter pylori in human gastric epithelial cells: role in epithelial cell migration. J. Cell Sci., 116: 3017-3026

Noble, P-J., Wilde,G., White,M.R.H., Pennington,S.R., Dockray,G.J. Varro,A. (2003). Stimulation of the gastrin-cholecystokininB receptor promotes migration of gastric AGS cells via multiple paracrine pathways. Am.J.Physiol. 284: G75-84

Varro, A., Hemers, E., Archer, D., Pagliocca,A., Haigh,C., Ahmed,S., Dimaline,R., Dockray, G.J. (2002) Identification of plasminogen activator inhibitor-2 as a gastrin-regulated gene: role of Rho GTPase and menin. Gastroenterology, 123: 271-280

Bishop, L., Dimaline,R., Blackmore,C., Deavall,D., Dockray,G.J. & Varro,A. (1998) Modulation of the cleavage of the gastrin precursor by phosphorylation. Gastroenterology, 115: 1154-1162.

Varro, A., Dockray,G.J., Bate,G., Vaillant, C., Higham,A., Armitage, E. & Thompson, D.G. (1997) Gastrin biosynthesis in the antrum of pernicious anaemia patients. Gastroenterology, 112:733-741.

Varro, A., Voronina, S. and Dockray, G.J. (1995). Pathways of processing of the gastrin precursor in rat antral mucosa. J.Clin.Invest., 95:1642-1649.

Varro, A., Henry, J., Vaillant, C. and Dockray, G.J. (1994). Discrimination between temperature- and brefeldin A-sensitive steps in the sulfation, phosphorylation and cleavage of progastrin and its derivatives. J. Biol. Chem., 269: 20764-20770.

Varro, A., Nemeth, J., Bridson, J., Lee, C., Moore, S., Dockray, G.J. (l990).  Processing of the gastrin precursor.  Modulation of phosphorylated, sulfated, and amidated products.  J. Biol. Chem., 265: 21476-21481.

Burdyga,G.; Varro,A.; Dimaline,R.; Thompson,D.G.; Dockray,G.J. Expression of cannabinoid CB1 receptors by vagal afferent neurons: kinetics and role in influencing neurochemical phenotype Am. J. Physiol., 299: G63-69.

Gonda TA, Varro A, Wang TC, Tycko B. (2010) Molecular biology of cancer-associated fibroblasts: can these cells be targeted in anti-cancer therapy? Semin Cell Dev Biol.21:2-10.

Xiao C, Ogle SA, Schumacher MA, Orr-Asman MA, Miller ML, Lertkowit N, Varro A, Hollande F, Zavros Y. (2010) Loss of parietal cell expression of Sonic hedgehog induces hypergastrinemia and hyperproliferation of surface mucous cells. Gastroenterology.138:550-61.

Wang JS, Varro A, Lightdale CJ, Lertkowit N, Slack KN, Fingerhood ML, Tsai WY, Wang TC, Abrams JA. (2010) Elevated Serum Gastrin Is Associated With a History of Advanced Neoplasia in Barrett's Esophagus. Am J Gastroenterol. 105:1039-45.

De Lartigue G, Dimaline R, Varro A, Raybould H, De La Serre CB, Dockray GJ. (2010) Cocaine- and Amphetamine-Regulated Transcript Mediates the Actions of Cholecystokinin on Rat Vagal Afferent Neurons. Gastroenterol. 138:1479-90.

de Lartigue,G.; Lur,G.; Dimaline,R.; Varro,A.; Raybould,H.; Dockray,G.J.EGR1 Is a Target for Cooperative Interactions between Cholecystokinin and Leptin, and Inhibition by Ghrelin, in Vagal Afferent Neurons. Endocrinology,151:1589-99.

Lassman DJ, McKie S, Gregory LJ, Lal S, D'Amato M, Steele I, Varro A, Dockray GJ, Williams SC, Thompson DG. (2010) Defining the Role of Cholecystokinin in the Lipid-Induced Human Brain Activation Matrix. Gastroenterol. 138:1514-24

Takaishi S, Tu S, Dubeykovskaya ZA, Whary MT, Muthupalani S, Rickman BH, Rogers AB, Lertkowit N, Varro A, Fox JG, Wang TC. (2009) Gastrin is an essential cofactor for helicobacter-associated gastric corpus carcinogenesis in C57BL/6 mice. Am J Pathol. 175:365-75.

Almeida-Vega, S., Catlow, K., Kenny, S., Dimaline, R., Varro, A. (2009) Gastrin activates paracrine networks leading to induction of PAI-2 via MAZ and ASC-1. Am. J. Physiol., 296: G414-23.

Jin G, Ramanathan V, Quante M, Baik GH, Yang X, Wang SS, Tu S, Gordon SA, Pritchard DM, Varro A, Shulkes A, Wang TC (2009) Inactivating cholecystokinin-2 receptor inhibits progastrin-dependent colonic crypt fission, proliferation, and colorectal cancer in mice. J Clin Invest. 119:2691-701.

Kenny, S., Duval,C., Sammut,S.J., Steele,I., Pritchard,D.M., Atherton,J.C., Argent,R.H., Dimaline,R., Dockray,G.J., Varro,A. (2008) Increased expression of the urokinase plasminogen activator system by Helicobacter pylori in gastric epithelial cells. Am. J. Physiol., 295: G431-89.

Jiang, L., Gonda T.A., Gamble, M.V., Salas, M., Seshan, V., Tu, S., Twaddell, W.S., Hegyi, P., Lazar, G., Steele, I., Varro, A., Wang, T.C., Tycko, B. (2008) Global hypomethylation of genomic DNA in cancer-associated myofibroblasts. Cancer Research, 68: 9900-8.

Pritchard DM, Berry D, Przemeck SM, Campbell FC, Edwards SW and Varro A (2008) Gastrin increases mcl-1 expression in type 1 gastric carcinoid tumors and a gastric epithelial cell line which expresses the CCK-2 receptor. Am J Physiol Gastrointest Liver Physiol 295:G798-805.

Varro A, Kenny S, Hemers E, McCaig C, Przemeck S, Wang TC, Bodger K and Pritchard DM (2007) Increased gastric expression of MMP-7 in hypergastrinemia and significance for epithelial-mesenchymal signaling. Am J Physiol Gastrointest Liver Physiol. 292:G1133-40.

Bodger K, Ahmed S, Michael A, Khan AL, Pazmany L, Pritchard DM, Dimaline R, Dockray GJ, Varro A. (2007) Altered gastric corpus expression of tissue inhibitors of metalloproteinases in human and murine Helicobacter infection. J. Clin. Pathol., 61: 72-78.

Steele I, Dimaline R, Pritchard DM, Peek R, Wang TC, Dockray GJ, Varro A. (2007) Helicobacter and gastrin stimulate Reg1 expression in gastric epithelial cells through distinct promoter. Am. J. Physiol., 293:G347-54.

McCaig C, Duval C, Hemers E, Steele I, Pritchard DM, Przemeck S, Dimaline R, Ahmed S, Bodger K, Kerrigan D, Wang TC, Dockray GJ and Varro A (2006) The role of matrix metalloproteinase (MMP)-7 in redefining the gastric microenvironment in response to Helicobacter pylori. Gastroenterology 130:1754-63.

Hemers E, Duval C, McCaig C, Handley M, Dockray GJ, Varro A. (2005) Insulin-like growth factor binding protein-5 is a target of matrix metalloproteinase-7: implications for epithelial-mesenchymal signalling. Cancer Res., 65:7363-7369.

	Biography	Role	Email	Telephone	Location
	Professor Andrea Varro	Professor of Physiology		+44(0)151 794 5331	Physiology Research Building
	Dr Islay Steele	Postdoctoral Research Fellow (NIHR)		+44(0)151 794 5339	Physiology Research Building
	Dr Chris Holmberg	Postdoctoral Research Fellow		+44(0)151 794 5335	Physiology Research Building
	Dr Andy Moore	Clinical Research Fellow (NIHR)		+44(0)151 794 5335	Physiology Research Building
	Nantaporn Lertkowit	PhD Student		+44(0)151 794 5335	Physiology Research Building
	Susanne Lyons	PhD Student		+44(0)151 794 5335	Physiology Research Building
	Silviya Balabanova	PhD Student		+44(0)151 794 5335	Physiology Research Building
	Liyi Wang	PhD Student		+44(0)151 794 5335	Physiology Research Building
	Dinesh Kumar	PhD Student		+44(0)151 794 5335	Physiology Research Building
	Ms Sandhir Kandola	PhD Student		+44(0)151 794 5335	Physiology Research Building