Background to research and synopsis

Non-alcoholic fatty liver disease (NAFLD) is an increasing burden to society, with its incidence growing in parallel with a general rise in obesity levels. Accurate assessment of NAFLD is crucial; fatty liver disease often referred to as the ‘silent killer’, since sufferers rarely present with symptoms until the disease has advanced to a stage where options for medical intervention are limited. In many individuals, fatty liver disease can progress through stages of inflammation to fibrosis, and eventually to cirrhosis and end stage liver disease. Whilst there are non- invasive methods to detect NAFLD such as ultrasound and magnetic resonance imaging (MRI), delineating between simple steatosis and more advanced stages of this progressive disease are extremely challenging.

A simple blood marker will be a less expensive alternative to imaging and will be applicable in populations where imaging is not available. Changes in mitochondrial activity (MBHI) in peripheral blood mononuclear cells and

platelets and assessment of extracellular vesicles (EV) will provide novel liver health markers. This project will establish reference population norms, monitor changes in response to lifestyle interventions, and identify patterns of changes in MBHI and EV to distinguish between simple fatty liver and more advanced disease states such as liver inflammation and fibrosis.

Recent publications by supervisors that are relevant to the project

  1. Chambers ES, Byrne CS, Rugyendo A, Morrison DJ, Preston T, Tedford MC, Bell JD, Thomas EL, Akbar AN, Riddell NE, Sharma R, Thursz MR, Manousou P and Frost G. The effects of dietary supplementation with inulin and inulin- propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease. Diabetes, Obes. Metab. 2019; 21(2): 372-376.

  2. Kosgodage US, Uysal-Onganer P, MacLatchy A, Mould R, Nunn AV, Guy GW, Kraev I, Chatterton NP, Thomas EL, Inal JM, Bell JD, Lange S. Cannabidiol affects Extracellular Vesicle release, miR21 and miR126, and reduces Prohibitin Protein in Glioblastoma Multiforme Cells. Transl Oncol. 2019; 12(3): 513-522.

  3. Mojtahed A, Kelly CJ, Herlihy AH, Kin S, Wilman HR, McKay A, Kelly M, Milanesi M, Neubauer S, Thomas EL, Bell JD, Banerjee R, Harisinghani M. Reference range of liver corrected T1 values in a population at low risk for fatty liver disease – a UK Biobank sub-study, with an appendix of interesting cases. Abdom. Radiol. (NY). 2019 Jan;44(1):72-84

  4. McKay A, Wilman HR, Dennis A, Kelly M, Gyngell ML, Neubauer S, Bell JD, Banerjee R and Thomas EL. Measurement of liver iron by magnetic resonance imaging in the UK Biobank population. PLOS One 2018; 13(12): e0209340.

  5. Buckley A, Thomas EL, Lessan N, Trovato FM, Trovato GM and Taylor-Robinson SD. Non-alcoholic fatty liver disease: relationship with cardiovascular risk markers and clinical endpoints. Diabetes Res. Clin. Pract. 2018; 144: 144-154.

  6. Kosgodage US, Mould R, Henley AB, Nunn AV, Guy GW, Thomas EL, Inal JM, Bell JD, Lange S. Cannabidiol (CBD) is a novel inhibitor for exosome and microvesicle (EMV) release in cancer. Front. Pharmacol. 2018; 9: 889.

  7. Fiamoncini J, Rundle M, Gibbons H, Thomas EL, Geillinger-Kästle K, Bunzel D, Trezzi JP, Kiselova-Kaneva Y, M Dwek 15/11/2018 edited 17/2/2018

Wopereis S, Wahrheit J, Kulling SE, Hiller K, Sonntag D, Ivanova D, van Ommen B, Frost G, Brennan L, Bell J, Daniel H. Plasma metabolome analysis identifies distinct human metabotypes in the postprandial state with different susceptibility to weight loss-mediated metabolic improvements. FASEB J. 2018; 32(10): 5447-5458

  1. Cobbold JFL, Atkinson S, Marchesi JR, Smith A, Wai SN, Stove J, Shojaee-Moradie F, Jackson N, Umpleby AM, Fitzpatrick J, Thomas EL, Bell JD, Holmes E, Taylor-Robinson SD, Goldin RD, Yee MS, Anstee QM, Thursz MR. Rifaximin in non-alcoholic steatohepatitis: an open-label pilot study. Hepatol. Res. 2018; 48(1): 69-77.

  2. Umpleby AM, Shojaee-Moradie F, Fielding B, Li X, Marino A, Alsini N, Isherwood C, Jackson N, Ahmad A, Stolinski M, Lovegrove JA, Johnsen S, Mendis A, Wright J, Wilinska ME, Hovorka R, Bell JD, Thomas EL, Frost GS, Griffin BA. Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets. Clin. Sci. 2017; 131(21): 2561-2573.

  3. Brody LP, Sahuri Arisoylu M, Parkinson JR, Parkes HG, So PW, Hajji N, Thomas EL, Frost GS, Miller AD and Bell JD. Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects. Int. J. Nanomed. 2017; 12: 6677-6685.

  4. Wilman HR, Kelly M, Garratt S, Matthews PM, Milanesi M, Herlihy A, Gyngell M, Neubauer S, Bell JD, Banerjee R, Thomas EL. Characterisation of liver fat in the UK Biobank cohort. PLoS One. 2017; 12(2): e0172921.

  5. Meienberg F, Yee M, Johnston D, Cox J, Robinson S, Bell JD, Thomas EL, Taylor-Robinson SD, Godsland I. Liver fat in adults with GH deficiency: comparison to matched controls and the effect of GH replacement. Clin. Endocrinol. (Oxf). 2016; 85(1): 76-84.

  6. Sahuri Arisoylu M, Brody L, Parkinson J, Parkes H, Navaratnam N, Miller A, Thomas EL, Frost G, and Bell JD. Reprogramming of hepatic fat accumulation and "browning" of adipose tissue by the short chain fatty acid acetate. Int. J. Obes. (Lond). 2016; 40(6): 955-63.

  7. CuthbertsonDJ,Shojaee-MoradieF,SprungVS,JonesH,PughCJ,RichardsonP,KempGJ,BarrettM,JacksonNC, Thomas EL, Bell JD, Umpleby AM. Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homeostasis in obese patients with Non-Alcoholic Fatty Liver Disease. Clin Sci (Lond). 2016; 130(2): 93-104

  8. GuessND,DornhorstA,OliverN,BellJD,ThomasEL,andFrostGS.Theeffectofinulinonweightmanagement and ectopic fat in subjects with prediabetes. Nutr Metab (Lond). 2015; 12: 36.

  9. Sam AH, Sleeth ML, Thomas EL, Ismail NA, Mat Daud N, Chambers E, Shojaee-Moradie F, Umpleby AM, Goldstone AP, Le Roux CW, Bech P, Busbridge M, Laurie R, Cuthbertson DJ, Buckley A, Ghatei MA, Bloom SR, Frost GS, Bell JD, Murphy KG.Circulating pancreatic polypeptide concentrations predict visceral and liver fat content. J. Clin. Endocrinol. Metab. 2015; 100(3): 1048-52.

  10. Cuthbertson DJ, Weickert MO, Lythgoe D, Sprung VS, Dobson R, Shoajee-Moradie F, Umpleby M, Pfeiffer AFH, Thomas EL, Bell JD, Jones H, Kemp GJ. External validation of the fatty liver index and lipid accumulation product indices, using 1H-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals. Eur. J. Endocrinol. 2014; 171(5), 561-569.


Informal enquiries: Louise Thomas
E: [email protected]

Entry requirements

Candidates should normally have a minimum classification of 2.1 in their Bachelor Degree or equivalent and preferably a Masters degree. Applicants whose secondary level education has not been conducted in the medium of English should also demonstrate evidence of appropriate English language proficiency normally defined as IELTS: 6.5 (overall score with not less than 6.0 in any of the individual elements).

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Please follow this link to apply for the programme most appropriate to your research, please note that the programme appears as MPhil on UCAS, however there is an option on the form to request PhD via MPhil, which is the standard route:

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Interviews will be held in June/July 2019. The Studentship title is SLS8 Full Scholarship and Fee Waiver School of Life Sciences. Please include this in your application, you must also list the Project Code in order for us to allocate your application to the correct.