Restoring brain health in steatotic liver disease

Start date: June 2025 (duration 36 months) 

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic multisystem disease, which affects ~30% of the general population and more than 80% of morbidly obese people. Studies have reported the negative effects that an unhealthy diet and obesity can have on brain function. It is now also known that MASLD increases the risk of developing depression, Parkinson’s and Alzheimer’s disease.

We recently found that accumulation of liver fat causes a decrease in oxygen to the brain and inflammation to brain tissue. Specifically, MASLD affected the number and thickness of brain blood vessels, delivering less oxygen, with brain cells consuming more oxygen due to inflammation. This led to lower brain oxygen levels, which alone could be responsible for the increase risk of dementia seen in MASLD patients.

This project will advance understanding of the abnormal physiological processes occurring in the brain during MASLD. By combining analysis of animal samples and human bio banked data, we will investigate whether brain blood vessel changes can be reversed by treating MASLD, or if the changes are irreversible.

The key knowledge derived from this research will be transformative and highlight the importance of the brain-liver axis. It will identify novel targets and effective strategies to improve brain health in patients with MASLD that will ultimately improve their quality of life and allow for healthy ageing.

General experimental plan:

Brain vasculature will be characterised by 3D immunofluorescent analysis using confocal, high resolution and light sheet microscopy, as well as in vivo two-photon microscopy.

Additional techniques that will be used in this project include:

· In vivo electrophysiology of vagal afferents

· Metabolomics and lipidomics

In order to investigate cerebrovascular and brain function in individuals with MASLD, human data from the UK Biobank, Whitehall II, and TwinsUK studies will be analysed

If you have relevant experience in any of the above techniques (desirable) please indicate it clearly in your application.

Contacts:

Queries on Project or academics:

Anna Hadjichambi a.hadjichambi@researchinliver.org.uk

Queries on applying: Shaleem Grant sims-student_queries@kcl.ac.uk 

Please apply via https://apply.kcl.ac.uk/

1) Register a new account and login.

2) Open a new application selecting a preferred entry date in accordance with the advert.

3) Search for the programme …

Immunology and Microbial Science Research MPhil/PhD

4) Complete and submit your application including the following:

· Include a supporting personal statement.

· References

· CV

· Indicate the supervisor’s name and project title when prompted during the application.

5) For funding, please select option 5 and type the Award scheme name: IOHAH123

Once you have applied you will need to follow admissions’ instructions and return their requested documents before your application can be passed to the school’s operations officer (education) for processing. Eligible candidates will be shortlisted and selected for a formal interview.

Please note, that the applications portal deadlines are for admissions to receive applications only and are separate to the closing date stated on this advert.