Bile acid metabolism in metabolic associated fatty liver disease (MAFLD) and hepatocellular carcinoma (HCC)

Oxford Brookes University
Faculty of Health and Life Sciences,
Department of Biomedical and Medical Sciences

3 Year, full-time PhD studentship

Project title: Bile acid metabolism in metabolic associated fatty liver disease (MAFLD) and hepatocellular carcinoma (HCC)

Eligibility: Home UK/EU and International students

Closing date: 11 December 2020

Start date: September 2021

Bursary p.a.: Bursary equivalent to UKRI national minimum stipend plus fees (2020/21 bursary rate is £15, 285)

University fees and bench fees at the UK rate will be met by the University for the 3 years of the Studentship.

Supervisors: Dr. Laura Gathercole, Prof. Jeremy Tomlinson (University of Oxford), Prof. Sue Vaughan, Prof. Dave Carter
Fees: Tuition fees up to UK level will be paid by the University. Any EU and international students awarded the studentship would need to cover the difference between international, EU and UK fees. Please note, fees increase by 4% annually.

Background
Patients with metabolic associated fatty liver disease (MAFLD) are at a greatly increased risk of hepatocellular carcinoma (HCC). Bile acids are steroid compounds that are synthesised in the liver and, acting through the bile acid receptor FXR, can activate hepatoprotective signalling pathways. However, the physical properties of bile acids mean that certain species are cytotoxic and cause oxidative stress.
It is known that bile acid homeostasis is altered in patients with MAFLD. We hypothesise that hepatic bile acid synthesis and metabolism are dysregulated and that this results in both an increase in the cytotoxicity of the bile acid pool and a loss of cytoprotective bile acid signalling, so promoting MAFLD progression and increasing the risk of developing HCC. Furthermore, that sex specific differences in the regulation, or dysregulation, of bile acid synthesis and metabolism contributes to the increased prevalence of MAFLD and HCC in males.

Workplan
The student will use in vivo and liver spheroid models, combined with molecular and state of the art bioimaging techniques, to investigate the impact that manipulating bile acid synthesis and metabolism has on oxidative stress, hepatoprotective signalling and carcinogenesis, as well as the mechanisms that underpin sex specific differences.

For informal inquiries about the project please contact Dr Laura Gathercole: [Email Address Removed]