Newcastle University

Introduction

For those looking for the "HEPATOCYTE USER GROUP" web site, please click on the URL above or go to: hug.ncl.ac.uk

Background

Research background in Toxicology and cytochromes P450. General interests are in the liver cell differentiation and liver disease.

Qualifications

BSc PhD

Previous Positions

2005-2006: Senior Lecturer – School of Medical Sciences, University of Aberdeen, UK.

2000-2005: Lecturer in Molecular and Cell Biology – Molecular and Cell Biology, University of Aberdeen, UK.

1997-2000: Wellcome Trust Research Fellow – Liver Group, Cell and Molecular Medicine,Southampton General Hospital, Southampton, UK.

1996: Visiting Research Fellow - Institute Gulbenkian de Ciencia, Oeiras, Portugal.

1995: Visiting Research Fellow - INSERM U128, Route de Mende, BP 5051 (CNRS), Montpellier 34033, France.

1994-1997: Post-Doctoral Research Fellow - Dept Toxicology, St. Bartholomew's Hospital Medical College, London, UK.

Memberships

Biochemical Society, British association Study of the Liver (BASL), British Toxicology Society (BTS).

Honours and Awards

British Association for the Study of the Liver – Young Investigator of the Year (2000).

Research Interests

Liver Biology, Liver Fibrosis, Stem/Progenitor Cells and the Liver

Other Expertise

Pharmacology, Toxicology

Current Work

Role of the PXR in modulating liver fibrosis; developing imaging techniques for liver fibrosis; Hepatocyte differentiation.

Postgraduate Supervision

Currently 4 PhD Students - in Liver Biology and Disease.

Esteem Indicators

Guest Editor - Special issues for the journal Toxicology (2007-2010)

Elected to the British Association for the Study of the Liver Committee (2001-2004).

Member of the Scientific Sub-Committee of the British Toxicology Society (2003-2008).

Member of the Executive Committee of the British Toxicology Society (2009- )

Funding

Wellcome Trust
MRC
BBSRC
EPSRC

Patents

Patent application - Co-applicant with Southampton Liver Group members (20-09-06). Use of apoptosis inducing agents in the preparation of a medicament for the treatment of liver diseases. GB0303735.

Patent Application -Wright MC, Porter A. (13-10-2005). WO2005095453. Specific binding members against synaptophysin - a human antibody to hepatic stellate cells for targeting drugs / imaging agents for liver fibrosis treatment.

Patent Application -Wright M.C. (03-04-2003). WO03026670. Compositions for therapy - a membrane-associated steroid binding protein is a therapeutic target for anti-fibrotic drugs.

Undergraduate Teaching

Pharmacology PED2001
Toxicology PED3011

Postgraduate Teaching

MRes in Medical & Molecular Biosciences PGY8003

• Wallace K, Shaw J, White SA, Wright S, Burt AD, Wright MC. Prolonged glucocorticoid exposure results in the appearance of hepatocytes in the adult pancreas. In: Journal of Hepatology: 46th Annual Meeting of the European Association for the Study of the Liver (EASL). 2011, Berlin, Germany: Elsevier BV.
• Wallace K, Long Q, Fairhall E, Charlton K, Wright MC. Serum- and glucorticoid-induced kinase 1 (SGK1) plays a key role in the glucocorticoid dependent trans-differentiation of a pancreatic progenitor cell to hepatocytes. In: Journal of Hepatology: 46th Annual Meeting of the European Association for the Study of the Liver (EASL). 2011, Berlin, Germany: Elsevier BV.
• Ebrahimkhani MR, Oakley F, Murphy LB, Mann J, Moles A, Perugorria MJ, Ellis E, Lakey AF, Burt AD, Douglass A, Wright MC, White SA, Jaffre F, Maroteaux L, Mann DA. Stimulating healthy tissue regeneration by targeting the 5-HT2B receptor in chronic liver disease. Nature Medicine 2011, 17(12), 1668-U189.
• Oakley F, Murphy L, Wright M, Mann D. Stimulation of lover regeneration and amelioration of fibrosis by antagonism of a 5-HT2B/ERK/JUND/TGF beta 1 signally pathway in hepatic stellate cell. In: Journal of Hepatology: 46th Annual Meeting of the European Association for the Study of the Liver (EASL). 2011, Berlin, Germany: Elsevier BV.
• Wallace K, Fairhall EA, Charlton KA, Wright MC. AR42J-B-13 cell: An expandable progenitor to generate an unlimited supply of functional hepatocytes. Toxicology 2010. ,278 3 277-287.
• Wright M. British Toxicology Society Special Reviews 2010. Toxicology 2010, 278(3), 249.
• Douglass A, Wallace K, Parr R, Park J, Durward E, Broadbent I, Barelle C, Porter A, Wright M. Corrigendum to "Antibody-targeted myofibroblast apoptosis reduces fibrosis during sustained liver injury" [J Hepatol 49 (2008) 88-98] (DOI:10.1016/j.jhep.2008.01.032). Journal of Hepatology 2010, 52(5), 779.
• Wallace K, Flecknell PA, Burt AD, Wright MC. Disrupted Pancreatic Exocrine Differentiation and Malabsorption in Response to Chronic Elevated Systemic Glucocorticoid. American Journal of Pathology 2010,177 3 1225-1232.
• Wallace K, Marek CJ, Hoppler S, Wright MC. Glucocorticoid-dependent transdifferentiation of pancreatic progenitor cells into hepatocytes is dependent on transient suppression of WNT signalling. Journal of Cell Science 2010, 123(12), 2102-2109.
• Wallace K, Cowie DE, Konstantinou DK, Hill SJ, Tjelle TE, Axon A, Koruth M, White SA, Carlsen H, Mann DA, Wright MC. The PXR is a drug target for chronic inflammatory liver disease. Journal of Steroid Biochemistry and Molecular Biology 2010, 120(2-3), 137-148.
• Wallace K, Marek CJ, Currie RA, Wright MC. Exocrine pancreas trans-differentiation to hepatocytes-A physiological response to elevated glucocorticoid in vivo. Journal of Steroid Biochemistry and Molecular Biology 2009, 116(1-2), 76-85.
• Marek CJ, Wallace K, Durward E, Koruth M, Leel V, Leiper LJ, Wright MC. Low affinity glucocorticoid binding site ligands as potential anti-fibrogenics. Comparative Hepatology 2009, 8(1), -.
• Axon A, Cowie DE, Mann DA, Wright MC. A mechanism for the anti-fibrogenic effects of the pregnane X receptor (PXR) in the liver: Inhibition of NF-κB?. Toxicology 2008. , 246(1), 40-44.
• Douglass A, Wallace K, Parr R, Park J, Durward E, Broadbent I, Barelle C, Porter A, Wright MC. Antibody-targeted myofibroblast apoptosis reduces fibrosis during sustained liver injury. Journal of Hepatology 2008, 49(1), 88-98.
• Hagens WI, Beljaars L, Mann DA, Wright MC, Julien B, Lotersztajn S, Reker-Smit C, Poelstra K. Cellular targeting of the apoptosis-inducing compound gliotoxin to fibrotic rat livers. Journal of Pharmacology and Experimental Therapeutics 2008, 324(3), 902-910.
• Wallace K, Burt A, Wright M. Liver fibrosis. Biochemical Journal 2008. , 411(1), 1-18.
• Douglass A, Wallace K, Koruth M, Barelle C, Porter AJ, Wright MC. Targeting liver myofibroblasts: a novel approach in anti-fibrogenic therapy. Hepatology International 2008, 2(4), 405-415.
• Marek CJ, Tucker SJ, Koruth M, Wallace K, Wright MC. Expression of CYP2S1 in human hepatic stellate cells. FEBS Letters 2007, 581(4), 781-786.
• Haughton EL, Tucker SJ, Marek CJ, Durward E, Leel V, Bascal Z, Monaghan T, Koruth M, Collie-Duguid E, Mann DA, Trim JE, Wright MC. Pregnane X Receptor Activators Inhibit Human Hepatic Stellate Cell Transdifferentiation In Vitro. Gastroenterology 2006,131 1 194-209.
• Wright MC. The impact of pregnane X receptor activation on liver fibrosis. Biochemical Society Transactions 2006, 34(6), 1119-1123.
• Elrick LJ, Leel V, Blaylock MG, Duncan L, Drever MR, Strachan G, Charlton KA, Koruth M, Porter AJ, Wright MC. Generation of a monoclonal human single chain antibody fragment to hepatic stellate cells - a potential mechanism for targeting liver anti-fibrotic therapeutics. Journal of Hepatology 2005,42 6 888-896.
• Oakley F, Meso M, Iredale JP, Green K, Marek CJ, Zhou X, May MJ, Millward-Sadler H, Wright MC, Mann DA. Inhibition of Inhibitor of κB Kinases Stimulates Hepatic Stellate Cell Apoptosis and Accelerated Recovery From Rat Liver Fibrosis. Gastroenterology 2005,128 1 108-120.
• Marek CJ, Tucker SJ, Konstantinou DK, Elrick LJ, Haefner D, Sigalas C, Murray GI, Goodwin B, Wright MC. Pregnenolone 16α carbonitrile inhibits rodent liver fibrogenesis via PXR-dependent and PXR-independent mechanisms. Biochemical Journal 2005,387 3 601-608.
• Leel V, Elrick LJ, Solares J, Ingram N, Charlton KA, Porter AJ, Wright MC. Identification of a truncated ratp28-related protein expressed in kidney. Biochemical and Biophysical Research Communications 2004,316 3 872-877.
• Orr JG, Leel V, Cameron GA, Marek CJ, Haughton EL, Elrick LJ, Trim JE, Hawksworth GM, Halestrap AP, Wright MC. Mechanism of Action of the Antifibrogenic Compound Gliotoxin in Rat Liver Cells. Hepatology 2004,40 1 232-242.
• Marek CJ, Cameron GA, Elrick LJ, Hawksworth GM, Wright MC. Generation of hepatocytes expressing functional cytochromes P450 from a pancreatic progenitor cell line in vitro. Biochemical Journal 2003, 370(3), 763-769.
• Wright MC, Issa R, Smart DE, Trim N, Murray GI, Primrose JN, Arthur MJ, Iredale JP, Mann DA. Gliotoxin Stimulates the Apoptosis of Human and Rat Hepatic Stellate Cells and Enhances the Resolution of Liver Fibrosis in Rats. Gastroenterology 2001, 121(3), 685-698.
• Vincent KJ, Jones E, Arthur MJ, Smart DE, Trim J, Wright MC, Mann DA. Regulation of E-box DNA binding during in vivo and in vitro activation of rat and human hepatic stellate cells. Gut 2001, 49(5), 713-719.
• Goodship J, Gill H, Carter J, Jackson A, Splitt M, Wright M. Autozygosity mapping of a Seckel Syndrome Locus to chromosome 3q22.1-q24. American Journal of Human Genetics 2000, 67(2), 498-503.
• Harvey JL, Paine AJ, Maurel P, Wright MC. Effect of the Adrenal 11-beta Hydroxylase Inhibitor Metyrapone on Human Hepatic Cytochrome P-450 gene Expression: Induction of Cytochrome P-450 3A4. Drug Metabolism and Disposition 2000, 28(1), 96-101.
• Hodgkinson CP, Wright MC, Paine AJ. Fibronectin mediated hepatocyte shape change reprograms cytochrome P450 2C11 gene expression via an integrin signalled induction of ribonuclease activity. Molecular Pharmacology 2000, 58(5), 976-981.
• Trim JE, Samra SK, Arthur MJ, Wright MC, McAulay M, Beri R, Mann DA. Upstream tissue inhibitor of metalloproteinases-1 (TIMP-1) element-1, a novel and essential regulatory DNA motif in the human TIMP-1 gene promoter, directly interacts with a 30-kDa nuclear protein. Journal of Biological Chemistry 2000, 275(9), 6657-63.
• M. J. Bahr,K. J. Vincent,M. J. Arthur,A. V. Fowler,D. E. Smart,M. C. Wright,I. M. Clark,R. C. Benyon,J. P. Iredale,D. A. Mann. Control of the tissue inhibitor of metalloproteinases-1 promoter in culture-activated rat hepatic stellate cells: regulation by activator protein-1 DNA binding proteins. Hepatology 1999, 29(3), 839-48.
• A. M. Elsharkawy,M. C. Wright,R. T. Hay,M. J. Arthur,T. Hughes,M. J. Bahr,K. Degitz,D. A. Mann. Persistent activation of nuclear factor-kappaB in cultured rat hepatic stellate cells involves the induction of potentially novel Rel-like factors and prolonged changes in the expression of IkappaB family proteins. Hepatology 1999, 30(3), 761-9.