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Queen Mary University of London

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The Brain Tumour Research Centre at Queen Mary University of London (QMUL) is a partnership between The Blizard Institute at QMUL, University College London (UCL), and The National Hospital for Neurology and Neurosurgery, Queen Square, London.  The team here focuses on research into glioblastoma multiforme (GBM), the most common and aggressive form of brain tumour in adults. 

Patients diagnosed with GBM 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 devastating 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?

 

GBM Stem Cell Research

 

Researchers at the Brain Tumour Research Centre of Excellence at QMUL are led by Professor Silvia Marino, one of the UK’s leading neuropathologists. In the five years since the Centre was established with funding from the Brain Tumour Research charity, they have set up an entirely new experimental research pipeline. It begins with the highly effective recruitment of patients at the National Hospital for Neurology and Neurosurgery, Queen Square, London who are willing to donate their brain tumour tissue during scheduled biopsies and surgeries. The tissue is used to derive individual tumour cells that can be grown in a petri dish and compared to normal, healthy brain cells from the same patient. Using a combination of laboratory work and artificial intelligence (sophisticated analytical computer programs) the team is already identifying key molecular differences that can potentially be exploited to find a cure.

 

Why are GBM stem cells so important?

 

GBMs are highly varied tumours that contain a mixture of different cells that vary in proportion from patient to patient, making it very difficult to find a “one drug fits all” answer to successfully treating them. In order to tackle this ultimate challenge, the team at QMUL are focused on studying a subset of cells known as glioblastoma multiforme (GBM) stem cells or glioma initiating cells (GIC) that share many features with normal neural stem cells (NSC) and have the ability to self-renew and grow. This property is thought to be what makes tumours resistant to treatment and to re-grow even when treatment initially appears to be going well, with devastating effects for everyone affected by this deadly form of cancer.

 

The next step is to validate the novel methods developed by this groundbreaking research, continue to identify the differences in tumour cells that can be targeted with drugs, and begin to test those likely to have the greatest success. The benefit of identifying such targets and then developing drugs to affect them is that healthy cells in the surrounding brain will be unharmed, hence reducing the risk of any side effects.

 

To develop a non-toxic cure lies at the heart of the research at this innovative Centre of Excellence. This project, which has a strong emphasis on how to develop individualised drug treatment regimes for patients in the future, is set to be of global significance in the race to find a cure for brain tumours, but without your help we can not build upon all that has been achieved so far and we risk losing the specialised researchers who are needed to complete the project into other, better funded areas of cancer research.

 


Publications

Merve A, Zhang X, Pomella N, Acquati S, Hoeck JD, Dumas A, Rosser G, Li Y, Jeyapalan J, Vicenzi S, Fan Q, Yang ZJ, Sabò A, Sheer D, Behrens A, Marino S. (2019) c-MYC overexpression induces choroid plexus papillomas through a T-cell mediated inflammatory mechanism. Acta Neuropathol Commun. 2019 May 29;7(1):95. doi: 10.1186/s40478-019-0739-x. 

Badodi S, Marino S, Guglielmi L (2019) Establishment and Culture of Patient-Derived Primary Medulloblastoma Cell Lines. Methods Mol Biol. 2019;1869:23-36. doi: 10.1007/978-1-4939-8805-1_3. 

Li N, Zhang Y, Sidlauskas K, Ellis M, Evans I, Frankel P, Lau J, El-Hassan T, Guglielmi L, Broni J, Richard-Loendt A, Brandner S (2018) Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades. Oncogene. 2018 Aug;37(31):4313-4333. doi: 10.1038/s41388-018-0277-1. 

Kurian KM, Jenkinson MD, Brennan PM, Grant R, Jefferies S,  Rooney AG, Bulbeck H, Erridge SC, Mills S, McBain C, McCabe MG, Price SG, Marino S, Moyes E, Qian W, Waldman A, Vaqas B, Keatley D, Burchill P, Watts C (2018) Brain tumor research in the United Kingdom: current perspective and future challenges. A strategy document from the NCRI Brain Tumor CSG. Neuro-Oncology Practice 5(1), 10–17, 2018 | doi:10.1093/nop/npx022 

Badodi S, Dubuc A, Zhang X, Rosser G, Da Cunha Jaeger M, Kameda-Smith MM, Morrissy AS, Guilhamon P, Suetterlin P, Li XN, Guglielmi L, Merve A, Farooq H, Lupien M, Singh SK, Basson MA, Taylor MD, Marino S. (2017) Convergence of BMI1 and CHD7 on ERK Signaling in Medulloblastoma. Cell Rep. 2017 Dec 5;21(10):2772-2784. doi: 10.1016/j.celrep.2017.11.021. 

Niklison-Chirou MV, Erngren I, Engskog M, Haglöf J, Picard D, Remke M, McPolin PHR, Selby M, Williamson D, Clifford SC, Michod D, Hadjiandreou M, Arvidsson T, Pettersson C, Melino G, Marino S. (2017) TAp73 is a marker of glutamine addiction in medulloblastoma. Genes Dev. 2017 Sep 1;31(17):1738-1753. doi: 10.1101/gad.302349.117. 

Badodi S, Dubuc A, Zhang X, Rosser G , Da Cunha Jaeger M, Kameda-Smith MM, Morrissy AS, Guilhamon P, Suetterlin P, LI X-N, Guglielmi L, Merve A, Farooq H, Lupien M, Singh SK, Basson MA, Taylor MD, Marino S (2017). Convergence of BMI1 and CHD7 on ERK signaling in medulloblastoma. Cell Reports. In press. DOI: 10.1016/j.celrep.2017.11.021

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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  • Wednesday 5th September
  • Wednesday 7th November

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