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Queen Mary University of London

We fund continuous and sustainable life-saving research at each of our centres

The Brain Tumour Research Centre of Excellence at Queen Mary University of London (QMUL) is located within the iconic Blizard Institute and works in partnership with University College London Institute of Neurology (UCL- ION).

The centre, launched in November 2014, is led by Prof Silvia Marino (QMUL) with her lead co-investigators Professor Sebastian Brandner (UCL- ION), Prof Denise Sheer (QMUL) and Dr Jeremy Rees (Consultant Neurologist at the National Hospital for Neurology and Neurosurgery).

The centre's research focuses on glioblastoma multiforme (GBM), the most common and aggressive form of brain tumour in adults. As there is no known cure or effective treatment for GBM, research in this area is a priority. 

Patients are currently treated with surgery, radiotherapy and chemotherapy, but these have limited effectiveness. Certain fundamental questions need to be addressed if we want to develop more effective treatments for this form of brain tumour. These include:

  • Where do the tumour cells originate from?
  • How do they develop?
  • How can we identify targets in these cells for new drugs to act on?

To answer these questions, the team are studying the cells of origin for the tumours and are trying to identify novel genes and pathways that control their behaviour. 

In particular, the researchers are looking at stem cells. These are found in every organ of the body and can develop into specialised cells, thus contributing to the maintenance and ‘regeneration’ of the organ. 

A subset of cells, known as glioblastoma stem cells or glioma initiating cells (GIC), share many features with normal neural stem cells (NSC). NSC are present in the brain and have the ability to self-renew and grow. The group is working to establish the difference between these tumour stem cells that keep multiplying – producing other tumour cells endlessly – and normal stem cells, which stop dividing when the body no longer needs new cells. 

Understanding how a tumour stem cell controls its proliferation will allow for the generation of more targeted drugs that specifically kill these cells in a more effective, much less toxic way.

Genetic differences directly affecting the genes themselves (i.e. a change in the DNA of the cells) play a key role in the development of tumour cells. In addition, the cells also have epigenetic changes which are associated with the addition of components onto the DNA, changing its structure and, therefore, influencing the structure and growth of the cells. 

However, in order to understand what these genetic changes are, the group needs to obtain tumour samples from people who are undergoing surgery to remove the tissue. 

Prof Silvia Marino said: “We’ve had over 100 patients generously donating tissue from their tumours for research and we successfully established conditions for the isolation and characterisation of both tumour stem cells and normal stem cells from the same patient. We have been inspired by meeting dedicated and committed supporters of the charity and of its very important cause.”  

The team at QMUL will focus on comparing the properties of normal and cancer stem cells to understand why the cells may become resistant to current treatments and use this information to develop novel drugs that will attack and kill these tumours. 

This is the first project of its kind  to directly compare matched GIC and NSC from the same patient. This will ensure that any difference between patients is eliminated and therefore the only changes observed will be associated with the tumour cell. This will make it easier to identify drug targets which may for the basis for the development of new and effective therapies.

 

Publications

Guillotin G, Austin P, Begum R, Freitas MO, Merve A, Brend T, Short SC, Marino S, Martin SA. (2016). Drug-repositioning screens identify Triamterene as a selective drug for the treatment of DNA Mismatch Repair deficient cells. Clin Cancer Res.Dec 2. [Epub ahead of print]

Blake SM, Stricker SH, Halavach H, Poetsch AR, Cresswell G, Kelly G, Kanu N, Marino S, Luscombe NM, Pollard SM, Behrens A. (2016) Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation. eLife: Mar 17;5. pii: e08711.

Merve A, Dubuc AM, Zhang X, Remke M, Baxter PA, Li XN, Taylor MD, Marino S. (2014) Polycomb group gene BMI1 controls invasion of medulloblastoma cells and inhibits BMP-regulated cell adhesion. Acta Neuropathol Commun. 2(1):10.

Acquati S, Greco A, Licastro D, Bhagat H, Ceric D, Rossini Z, Grieve D, Shaked-Rabi M, Henriquez NV, Brandner S, Stupka E, Marino S. Epigenetic regulation of Survivin by Bmi1 is cell type specific during corticogenesis and in gliomas. Stem Cells 31(1):190-202            

Behesti H, Bhagat H, Dubuc A, Taylor M, Marino S (2013). Bmi1 overexpression in the cerebellar granule cell lineage affects cell proliferation and survival without initiating medulloblastoma formation. Dis Model Mech 6(1):49-63          

 

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