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Staff Profile

Professor Loranne Agius

Professor of Metabolic Biochemistry

Background

Roles and Responsibilities

Principal Investigator for research on liver metabolism in Non-alcoholic fatty liver disease (NAFLD) with focus on intracellular homeostasis and impact of calorie excess and genetic variants as risk factors for liver disease, and development of new drugs for NAFLD. Research projects funded by MRC, MICA Exploring a new perspective on the mechanism of action of Glucokinase Activators in liver: a preclinical study (2017-2020); Targeting glucose metabolism in Nonalcoholic fatty liver disease (2018-2020).

Qualifications

D.Sc. Oxon, 2003
D.Phil. Oxon, 1981
M.Sc. University of Malta, 1978
B.Sc. University of Malta, 1977

Previous Positions

1978 - 81: Commonwealth Scholar, University of Oxford
1981 - 82: Postdoctoral Fellow, State University of Utrecht
1982 - 86: Postdoctoral Fellow, University of Â鶹´«Ã½
1986 - 91: Lecturer, University of Â鶹´«Ã½
1991 - 94: Senior Lecturer, University of Â鶹´«Ã½
1994 - 03: Reader, University of Â鶹´«Ã½

Memberships

Diabetes UK and Biochemical Society.

Research

Research Interests

Liver carbohydrate and lipid metabolism in health and disease with focus on Glucokinase and its regulatory protein, cellular metabolite homeostasis, metabolic control of gene expression in Nonalcoholic fatty liver disease (NAFLD), development of new drugs for NAFLD targeting liver glucose metabolism and intracellular homeostasis.  Validation of new mouse models for common human GCKR variants (e.g. rs1260326).  Mechanism of action of Glucokinase Activators during chronic therapy and development of new glucokinase targeting ligands for control of blood glucose homeostasis.

Other Expertise

Mechanism of action of anti-hyperglycaemic compounds and development of in vitro methods for screening mode of action.

Future Research

Preclinical studies on drug development for NAFLD.

Research Roles

Principal Investigator on two MRC Project Grants on mechanism of action of candidate drugs for NAFLD.

Funding

Current Research Funding is from: the Medical Research Council


Collaboration

Development of new Glucokinase targeting ligands is in collaboration with Dr. Celine Cano, School of Natural and Environmental Sciences.


Recent Publications


Agius L, Chachra SS, Ford BE. The Protective Role of the Carbohydrate Response Element Binding Protein in the Liver: The Metabolite Perspective. Front Endocrinol (Lausanne). 2020 Nov 17;11:594041.

 Ford BE, Chachra SS, Alshawi A, Brennan A, Harnor S, Cano C, Baker DJ, Smith DM, Fairclough RJ, Agius L. Chronic glucokinase activator treatment activates liver Carbohydrate response element binding protein and improves hepatocyte ATP homeostasis during substrate challenge. Diabetes Obes Metab. 2020;22(11):1985-1994.

 

Agius L, Ford BE, Chachra SS. The Metformin Mechanism on Gluconeogenesis and AMPK Activation: The Metabolite Perspective. Int J Mol Sci. 2020;21(9):3240. doi: 10.3390/ijms21093240. PMID: 32375255; PMCID: PMC7247334.

Teaching

Undergraduate Teaching:   Biomedical Sciences, Stage 2, Membrane Transport and Cell Signalling in Health and Disease, (PSC2002).  Postgraduate Teaching:  MRES Modules on Cell Signalling and Diabetes.

Publications

  • Articles

    • Ford BE, Chachra SS, Rodgers K, Moonira T, Al-Oanzi ZH, Anstee QM, Reeves HL, Schattenberg JM, Fairclough RJ, Smith DM, Tiniakos D, Agius L. . Molecular Metabolism 2023, 72, 101722.
    • Leitch AC, Abdelghany TM, Charlton A, Grigalyte J, Oakley F, Borthwick LA, Reed L, Knox A, Reilly WJ, Agius L, Blain PG, Wright MC. . Ecotoxicology and Environmental Safety 2020, 202, 110902.
    • Moonira T, Chachra SS, Ford BE, Marin S, Alshawi A, Adam-Primus NS, Arden C, Al-Oanzi ZH, Foretz M, Viollet B, Cascante M, Agius L. . Journal of Biological Chemistry 2020, 295(10), 3330-3346.
    • Ford BE, Chachra SS, Alshawi A, Brennan A, Harnor S, Cano C, Baker DJ, Smith DM, Fairclough RJ, Agius L. . Diabetes, Obesity and Metabolism 2020, 22(11), 1985-1994.
    • Alshawi A, Agius L. . Journal of Biological Chemistry 2019, 294(8), 2839-2853.
    • Barr D, Szennyes E, Bokor E, Al-Oanzi ZH, Moffatt C, Kun S, Docsa T, Sipos A, Davies MP, Mathomes RT, Snape TJ, Agius L, Somsak L, Hayes JM. . ACS Chemical Biology 2019, 14(7), 1460-1470.
    • Leitch AC, Lakey AF, Hotham WE, Agius L, Kass GE, Blain PG, Wright MC. . Biochemical and Biophysical Research Communications 2018, 503(3), 2167-2178.
    • Codner GF, Mianne J, Caulder A, Loeffler J, Fell R, King R, Allan AJ, Mackenzie M, Pike FJ, McCabe CV, Christou S, Joynson S, Hutchison M, Stewart ME, Kumar S, Simon MM, Agius L, Anstee QM, Volynski KE, Kullmann DM, Wells S, Teboul L. . BMC Biology 2018, 16(1), 70.
    • Codner GF, Mianné J, Caulder A, Loeffler J, Fell R, King R, Allan AJ, Mackenzie M, Pike FJ, McCabe CV, Christou S, Joynson S, Hutchison M, Stewart ME, Kumar S, Simon MM, Agius L, Anstee QM, Volynski KE, Kullmann DM, Wells S, Teboul L. . BioMedCentral Biology 2018, 16, 70.
    • Al-Oanzi ZH, Fountana S, Moonira T, Tudhope SJ, Petrie JL, Alshawi A, Patman G, Arden C, Reeves HL, Agius L. . Diabetes, Obesity and Metabolism 2017, 19(8), 1078-1087.
    • Agius L. . Proceedings of the Nutrition Society 2016, 75(1), 10-18.
    • Probert PM, Chung GW, Cockell SJ, Agius L, Mosesso P, White SA, Oakley F, Brown CD, Wright MC. . Toxicological Sciences 2014, 137(2), 350-370.
    • Parmenopoulou V, Kantsadi AL, Tsirkone VG, Chatzileontiadou DSM, Manta S, Zographos SE, Molfeta C, Archontis G, Agius L, Hayes JM, Leonidas DD, Komiotis D. . Bioorganic & Medicinal Chemistry 2014, 22(17), 4810-4825.
    • Cullen KS, Al-Oanzi ZH, O'Harte FPM, Agius L, Arden C. . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2014, 1843(6), 1123-1134.
    • Petrie JL, Patman GL, Sinha I, Alexander TD, Reeves HL, Agius L. . American Journal of Physiology 2013, 305(10), E1255-E1265.
    • Bechmann LP, Vetter D, Ishida J, Hannivoort RA, Lang UE, Kocabayoglu P, Fiel MI, Muñoz U, Patman GL, Ge F, Yakar S, Li X, Agius L, Lee YM, Zhang W, Hui KY, Televantou D, Schwartz GJ, Leroith D, Berk PD, Nagai R, Suzuki T, Reeves HL, Friedman SL. . Journal of Hepatology 2013, 58(5), 1000-1006.
    • Agius L. . Biochemical Pharmacology 2013, 85(3), 306-312.
    • Petrie JL, Al-Oanzi ZH, Arden C, Tudhope SJ, Mann J, Kieswich J, Yaqoob MM, Towle HC, Agius L. . Molecular and Cellular Biology 2013, 33(4), 725-738.
    • Arden C, Tudhope SJ, Petrie JL, Al-Oanzi ZH, Cullen KS, Lange AJ, Towle HC, Agius L. . Biochemical Journal 2012, 443(1), 111-123.
    • Tudhope SJ, Wang CC, Petrie JL, Potts L, Malcomson F, Kieswich J, Yaqoob MM, Arden C, Hampson LJ, Agius L. . Diabetes 2012, 61(1), 49-60.
    • Cullen KS, Matschinsky FM, Agius L, Arden C. . Diabetes 2011, 60(12), 3175-3185.
    • Arden C, Petrie JL, Tudhope SJ, Al-Oanzi Z, Claydon AJ, Beynon RJ, Towle HC, Agius L. . Diabetes 2011, 60(12), 3110-3120.
    • Marin de Mas I, Selivanov VA, Marin S, Roca J, Oresic M, Agius L, Cascante M. . BMC Systems Biology 2011, 5(1), 175.
    • Hampson LJ, Mackin P, Agius L. . Diabetologia 2007, 50(8), 1743-1751.
    • Payne VA, Arden C, Lange AJ, Agius L. . American Journal of Physiology - Regulatory Integrative and Comparative Physiology 2007, 293(2), R618-R625.
    • Arden C, Trainer A, De La Iglesia N, Scougall KT, Gloyn AL, Lange AJ, Shaw J, Matschinsky FM, Agius L. . Diabetes 2007, 56(7), 1773-1782.
    • Aiston S, Hampson LJ, Arden C, Iynedjian PB, Agius L. . Diabetologia 2006, 49(1), 174-182.
    • Harndahl L, Schmoll D, Herling AW, Agius L. . FEBS Journal 2006, 273(2), 336-346.
    • Arden C, Green AR, Hampson LJ, Aiston S, Harndahl L, Greenberg CC, Brady MJ, Freeman S, Poucher SM, Agius L. . FEBS Journal 2006, 273(9), 1989-1999.
    • Oikonomakos NG, Tiraidis C, Leonidas DD, Zographos SE, Kristiansen M, Jessen CU, Norskov-Lauritsen L, Agius L. . Journal of Medicinal Chemistry 2006, 49(19), 5687-5701.
    • Arden C, Baltrusch S, Agius L. . FEBS Letters 2006, 580(8), 2065-2070.
    • Hampson LJ, Arden C, Agius L, Ganotidis M, Kosmopoulou MN, Tiraidis C, Elemes Y, Sakarellos C, Leonidas DD, Oikonomakos NG. . Bioorganic and Medicinal Chemistry 2006, 14(23), 7835-7845.
    • Hampson LJ, Agius L. . Diabetes 2005, 54(3), 617-623.
    • Payne VA, Arden C, Wu C, Lange AJ, Agius L. . Diabetes 2005, 54(7), 1949-1957.
    • Green AR, Aiston S, Greenberg CC, Freeman S, Poucher SM, Brady MJ, Agius L. . Journal of Biological Chemistry 2004, 279(45), 46474-46482.
    • Brocklehurst KJ, Payne VA, Davies RA, Carroll D, Vertigan HL, Wightman HJ, Aiston S, Waddell ID, Leighton B, Coghlan MP, Agius L. . Diabetes 2004, 53(3), 535-541.
    • Aiston S, Green A, Mukhtar M, Agius L. . Biochemical Journal 2004, 377(1), 195-204.
    • Arden C, Harboottle A, Baltrusch S, Tiedge M, Agius L. . Diabetes 2004, 53(9), 2346-2352.
    • Brocklehurst KJ, Davies RA, Agius L. . Biochemical Journal 2004, 378(2), 693-697.
    • Tavridou A, Agius L. . FEBS Letters 2003, 551(1-3), 87-91.
    • Aiston S, Coghlan MP, Agius L. . European Journal of Biochemistry 2003, 270(13), 2773-2781.
    • Aiston S, Andersen B, Agius L. . Diabetes 2003, 52(6), 1333-1339.
    • Latsis T, Andersen B, Agius L. . Biochemical Journal 2002, 368, 309-316.
    • De Atauri P, Acerenza L, Kholodenko BN, De La Iglesia N, Guinovart JJ, Agius L, Cascante M. . Biochemical Journal 2001, 355(3), 787-793.
    • Aiston S, Hampson L, Gomez-Foix AM, Guinovart JJ, Agius L. . Journal of Biological Chemistry 2001, 276(26), 23858-23866.
    • Cascante M, Centelles JJ, Agius L. . Biochemical Journal 2000, 352(3), 899-905.
    • De La Iglesia N, Mukhtar M, Seoane J, Guinovart JJ, Agius L. . Journal of Biological Chemistry 2000, 275(14), 10597-10603.
    • Stubbs M, Aiston S, Agius L. . Diabetes 2000, 49(12), 2048-2055.
    • Agius L, Stubbs M. . Biochemical Journal 2000, 346(2), 413-421.
    • Aiston S, Peak M, Agius L. . Diabetologia 2000, 43(5), 589-597.
    • Aiston S, Agius L. . Diabetes 1999, 48(1), 15-20.
    • Dixon M, Agius L, Yeaman SJ, Day CP. . Hepatology 1999, 29(5), 1418-1424.
    • Aiston S, Trinh KY, Lange AJ, Newgard CB, Agius L. . Journal of Biological Chemistry 1999, 274(35), 24559-24566.
    • Mukhtar M, Stubbs M, Agius L. . FEBS Letters 1999, 462(3), 453-458.
    • L. Agius. The physiological role of glucokinase binding and translocation in hepatocytes. Advances in Enzyme Regulation, Vol 38 1998, 38, 303-331.
    • G. H. Thoresen, T. K. Guren, D. Sandnes, M. Peak, L. Agius and T. Christoffersen. Response to transforming growth factor or (TGF alpha) and epidermal growth factor (EGF) in hepatocytes: Lower EGF receptor affinity of TGF alpha is associated with more sustained activation of p42/p44 mitogen-activated protein kinase and greater efficacy in stimulation of DNA synthesis. Journal of Cellular Physiology 1998, 175, 10-18.
    • W. Lowes, M. Walker, K. Alberti and L. Agius. Hexokinase isoenzymes in normal and cirrhotic human liver: suppression of glucokinase in cirrhosis. Biochimica Et Biophysica Acta-General Subjects 1998, 1379, 134-142.
    • L. Agius. Involvement of glucokinase translocation in the mechanism by which resorcinol inhibits glycolysis in hepatocytes. Biochemical Journal 1997, 325, 667-673.
    • L. Agius. Substrate modulation at aldolase B binding in hepatocytes. Biochemical Journal 1996, 315, 651-658.
    • L. Agius, M. Peak, C. B. Newgard, A. M. GomezFoix and J. J. Guinovart. Evidence for a role of glucose-induced translocation of glucokinase in the control of hepatic glycogen synthesis. Journal of Biological Chemistry 1996, 271, 30479-30486.

  • Book Chapter

    • Agius L. . In: John E. Hesketh and Ian F. Pryme, ed. Cytoskeleton in Specialized Tissues and in Pathological States. London: JAI Press, 1996, pp.71-106.

  • Conference Proceedings (inc. Abstracts)

    • Moonira TN, Al-Oanzi Z, Arden C, Agius L. . In: Diabetes UK Professional Conference 2016. 2016, Glasgow, UK: Wiley-Blackwell.
    • Al-Oanzi Z, Fountana S, Agius L. . In: Diabetes UK Professional Conference. 2015, London, UK: Wiley-Blackwell Publishing Ltd.
    • Petrie JL, Fountana S, Agius L. . In: Diabetes UK Professional Conference 2014. 2014, Liverpool, UK: Wiley-Blackwell.
    • Arden C, Cullen KS, Al-Oanzi ZH, O'Harte FP, Agius L. . In: Diabetes UK Professional Conference. 2013, Manchester, UK: Wiley-Blackwell.
    • Daniele GA, Reeves HL, Agius L, Gaggini M, Comassi M, Miccoli R, Del Prato S, Gastaldelli A. . In: 48th General Assembly of the European Association for the Study of Diabetes. 2012, Berlin, Germany: Springer.
    • Al-Oanzi ZH, Petrie JL, Tudhope S, Arden C, Agius L. . In: 48th General Assembly of the European Association for the Study of Diabetes. 2012, Berlin, Germany: Springer.
    • Bechmann LP, Vetter D, Hannivoort RA, Patman G, Lee UE, Fiel MI, Agius L, Reeves H, Friedman SL. . In: 61st Annual Meeting of the American Association for the Study of Liver Diseases. 2010, Boston, MA: Hepatology: Wiley-Blackwell.
    • Agius L, Centelles J, Cascante M. . In: Biochemical Society Transactions: Meeting on High-Throughput Screening - The Way Ahead. 2002, Bedford, UK: Portland Press Ltd.
    • Agius L, Aiston S, Newgard CB. . In: NATO Advanced Research Workshop on Technological and Medical Implications of metabolic Control Analysis. 2000, Visegrad, Hungary: Springer.
    • Agius L. . In: FASEB Journal. 1999, Federation of American Societies for Experimental Biology.

  • Editorial

    • Agius L. . Expert Opinion on Therapeutic Patents 2014, 24(11), 1155-1159.

  • Letter

    • Agius L. . Diabetes Care 2012, 35(12), E90-E90.

  • Reviews

    • Agius L, Chachra SS, Ford BE. . Frontiers in Endocrinology 2020, 11, 594041.
    • Agius L, Ford BE, Chachra SS. . International Journal of Molecular Sciences 2020, 21(9), 3240.
    • Agius L. . Annual Review of Nutrition 2016, 36, 389-415.
    • Agius L. . Molecular Aspects of Medicine 2015, 46, 34-45.