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University of Plymouth

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

Our Centre of Excellence at the University of Plymouth is one of Europe’s leading research Institutes for low-grade brain tumours.

The Plymouth team, led by Prof Oliver Hanemann, has a world-leading track record in researching low-grade brain tumours occurring in teenagers and adults. By identifying and understanding the mechanism that makes a cell become cancerous, the team are exploring ways to halt or reverse them. 

Personalised medicine for low-grade brain tumours

The Brain Tumour Research Centre in Plymouth focuses on the emerging area of personalised medicine in order to provide new understanding of specific groups of common, low-grade brain tumours. The pioneering research team is looking at astrocytoma, oligodendroglioma, schwannoma, meningioma and ependymoma brain tumours. The research at Plymouth also has the potential to inform work on other brain tumour types, including high-grade tumours such as glioblastoma multiforme (GBM), but in fact meningioma alone accounts for over 30% of brain tumour patients diagnosed worldwide with a primary brain tumour.

Brain tumour types

Low-grade brain tumours: the underfunded of the underfunded

Research into brain tumours has historically been underfunded, and with much of that investment focused on high-grade brain tumours, it is vital that we keep the supply of funds channelled into Plymouth to support Professor Hanemann and his visionary team who are determined to change the lives of all those affected by these devastating low-grade tumour types. 

This includes the children and teenagers who have a condition called Neurofibromatosis 2. Meningiomas and schwannomas are two common brain tumours that form both spontaneously and also when associated with this incredibly challenging disease: and the NF2 gene at the heart of both is a particular area of focus for this compassionate team of researchers.


Working collaboratively with neurosciences 

Collaboration is key and it is something that we and our Member Charities value and promote. It is also an important element of the network of experts in brain tumour research that they too collaborate to increase the knowledge and bring us faster to a cure.

All the Brain Tumour Research teams at the University of Plymouth share laboratory space with researchers working on other forms of cancer, infection, immunity, and clinical neuroscience projects, thereby ensuring knowledge sharing across the disciplines so that advances in one area can potentially move others forward. They collaborate with other research teams both within the UK and internationally, and are active members of both the International Consortium of Meningioma (ICOM) and the British Irish Meningioma Society, regularly presenting their work at global conferences.


Low-grade research projects at Plymouth

Our Low-Grade Brain Tumour Centre of Excellence provides a vibrant hub for teams of dedicated researchers who have been attracted from across the globe to work at this innovative institution. Each team investigates different types of low-grade brain tumours, or different aspects of their neurobiology.


Building strong foundations for research:

 

Specialised tissue bank for low-grade brain tumours

Research can only happen if there are tumour samples for the researchers to study. The University of Plymouth Brain Tissue Biobank has grown significantly to over 300 samples, 98.7% of which are low-grade. The focus is on meningioma and schwannoma, with some astrocytoma and ependymoma. 

In order to support their current research, they are also collaborating with the Brain Tumour Research charity funded virtual tissue bank, BRAIN UK, and are receiving further glioma/astrocytoma samples from neuropathology departments across the UK.

With more funds for extra staff and resources, they could expand their vital Biobank even further.

The future of low-grade brain tumour tissue banking

The researchers at Plymouth need to expand their tissue bank to include more tissue samples. This would enable them to define further subgroups of meningioma, and also to include low-grade astrocytoma, ependymoma and oligodendroglioma tumours. 

Classifying meningioma for personalised medicine treatments

Tissue samples within the University of Plymouth Brain Tissue Biobank have enabled Professor Hanemann’s team to contribute to the development of new ways of classifying meningioma that have now been adopted worldwide. They have undertaken the genotyping of meningioma samples covering the main mutations in this tumour type, enabling the stratification of meningiomas that provides the basic requirement for research into precision medicine approaches, helping to move forward the global understanding of this new approach to brain tumour treatment.

 

Developing a blood test for Meningioma 

Professor Oliver Hanemann is developing a test on tissue or blood that can be used instead of a biopsy to identify markers that predict how meningiomas are likely to behave. The immediate benefit for some patients is avoiding invasive surgery. For other patients, a biopsy may be impossible due to the position of the tumour and the risks that this surgical procedure would bring, so this test will be able to provide crucial information that their medical team would otherwise not be able to obtain.

Finding new drug targets for Meningoma

Thanks to information gleaned from the innovative blood tests and extensive tumour tissue bank that has been established at University of Plymouth, the team are already finding new biomarkers that differentiate lower and higher-grade tumours, or indicate progression from lower to higher grade. These biomarkers are molecules found in brain tumour tissue or the patient’s blood and can be measured to indicate the progression of the disease, or identify what type of process has gone wrong to cause that disease. Biomarkers can also potentially be targeted by reformulated, repurposed or new drugs in order to influence the way that tumours develop, potentially holding tumours at the low-grade stage, shrinking them or ideally curing them altogether.

Identifying drugs to treat Meningioma

The team at Plymouth are busy testing reformulated and repurposed drugs on meningiomas in the laboratory, ready to move the most promising ones into clinical trials. They have already completed one phase 0 clinical trial that ruled out one potential compound, and are now focused on another promising formulation. The advantage of re-purposing existing drugs in this way is that if they already have a proven safety track record in humans, they can be moved more quickly into clinical trials than a new drug. The team will also be considering reformulations of such drugs, as it may be that a slight change to an existing drug may enhance effectiveness in this new situation.

The future of Meningioma research

There are currently no chemotherapy drugs that are routinely offered to patients due to their lack of effectiveness, yet existing regimes of surgery and radiotherapy often bring with them lifelong side effects. Researchers at the Brain Tumour Research Centre of Excellence in Plymouth are developing blood tests and biomarkers that will enable each subtype of meningioma to be treated with a personalised drug treatment that ensures maximum benefit with minimal side effects. New, reformulated or repurposed drugs that target only the cancer cells are being designed to avoid the damage currently done to healthy cells by standard chemotherapy regimes, hence reducing or avoiding side effects. They desperately need to expand their teams in order to speed up their vital research and bring us closer to a cure as quickly as possible.

 

Neurofibromatosis 2

Professor Hanemann and Dr. Silwia Ammoun’s teams are determined to find a cure that benefits not just those with a primary brain tumour, but also the children and teenagers who are diagnosed with Neurofibromatosis 2. They are leading the way in research into a mutation on a gene called NF2 (a “tumour suppressor” gene) found in most paediatric and adult schwannomas, meningiomas and spinal ependymomas that can give rise to this genetic disease called Neurofibromatosis 2. This research is partly supported by a grant given by Sparks and Great Ormond Street Hospital Charity National Funding. 

The future of Neurofibromatosis 2 Research

Children with Neurofibromatosis 2 will have developed multiple brain, spinal and nervous system tumours by the time they are teenagers, with the average prognosis being just 15 years from when the disease is first discovered. The team believe that finding a cure for low-grade brain tumours will also unblock the path to finding a cure for Neurofibromatosis 2.

Inflammation in meningioma and schwannoma brain tumours

Professor David Parkinson’s team are focused on the role that macrophages (a type of immune cell) play in fuelling inflammation, and hence the growth of both meningioma and schwannoma tumours. They have discovered some similarities with signalling pathways currently being investigated in glioblastome multiforme (GBM) and are exploring whether they may be some beneficial cross-fertilisation of knowledge across these different tumour types.

The future of inflammatory pathway research 

The Brain Tumour Centre of Excellence at Plymouth need to expand their work to explore these pathways in more detail, and to clarify the role of a wider range of substances produced by macrophages that may be key factors in driving tumour cell proliferation. With your help, they could expand their research across the boundaries between low and high-grade brain tumours.

New drugs for low-grade gliomas

Professor Ji-Liang Li leads the team who are working towards a combination therapy of temozolomide plus drugs that target the tumour micro-environment in low-grade astrocytomas. For example, they are investigating drugs that affect the blood vessels that develop in the environment directly around the tumour, which can then carry nutrients in the blood to help the tumour grow: by blocking the growth of these vessels, the tumour can potentially be starved of the fuel that drives progression to a higher grade.

The future of drug screening for low-grade brain tumours

These low-grade brain tumour experts need to expand their team working on new drug combinations for low-grade gliomas, enabling research to move more quickly towards clinical trials and hence provide a desperately needed opportunity for patients to explore such novel combination therapies.

They also want to build on their understanding of meningioma by screening drugs currently used for other diseases that may be effective against other low-grade tumour types, so that research on all of them moves forward together.

Low-Grade to High-Grade: Tumour Genesis and Transformation

Dr. Claudia Barros and her team are using a brain tumour model in Drosophila fruit flies to study tumour-initiating cells. The team has identified genes that trigger the development of all grades of glioma brain tumours: astrocytoma, oligodendroglioma and glioblastoma multiforme (GBM). By understanding how normal cells develop into tumour-initiating cells and then keep on fuelling those tumours, new treatments to target these cells can be developed.

The future of low-grade glioma research

The team need to deepen their focus on one particular gene and the pathway that it controls to help trigger the development of all grades of glioma brain tumours: astrocytoma, oligodendroglioma and glioblastoma multiforme (GBM), whilst continuing to explore other promising avenues of research.

 

Publications

Dong N, Shi X, Wang S, Gao Y, Huang Z, Xie Q, Li Y, Deng H, Wu Y, Li M, Li JL. (2019): M2 macrophages mediate sorafenib resistance by secreting HGF in a feed-forward manner in hepatocellular carcinoma. Br J Cancer. 2019 Jul;121(1):22-33. doi: 10.1038/s41416-019-0482-x.

Gil-Ranedo J, Gonzaga E, Jaworek KJ, Berger C, Bossing T, Barros CS. (2019) STRIPAK Members Orchestrate Hippo and Insulin Receptor Signaling to Promote Neural Stem Cell Reactivation. Cell Rep. 2019 Jun 4;27(10):2921-2933.e5. doi: 10.1016/j.celrep.2019.05.023. 

Dun XP, Carr L, Woodley PK, Barry RW, Drake LK, Mindos T, Roberts SL, Lloyd AC, Parkinson DB.(2019) Macrophage-Derived Slit3 Controls Cell Migration and Axon Pathfinding in the Peripheral Nerve Bridge. Cell Rep. 2019 Feb 5;26(6):1458-1472.e4. doi: 10.1016/j.celrep.2018.12.081. 

Dunn J, Ferluga S, Sharma V, Futschik M, Hilton DA, Adams CL, Lasonder E, Hanemann CO. (2019) Proteomic analysis discovers the differential expression of novel proteins and phosphoproteins in meningioma including NEK9, HK2 and SET and deregulation of RNA metabolism. EBioMedicine. 2019 Feb; 40:77-91. doi: 10.1016/j.ebiom.2018.12.048. 

Ammoun S, Evans DG, Hilton DA, Streeter A, Hayward C, Hanemann OC (2019) Phase 0 trial investigating the intratumoural concentration and activity of Sorafenib in neurofibromatosis type 2 Journal of Neurology, Neurosurgery & Psychiatry. Published Online First: 04 February 2019. doi: 10.1136/jnnp-2018-319713

Suppiah S, Nassiri F, Bi WL, Dunn IF, Hanemann CO, Horbinski CM, Hashizume R, James CD, Mawrin C, Noushmehr H, Perry A, Sahm F, Sloan A, Von Deimling A, Wen PY, Aldape K, Zadeh G (2019) International Consortium on Meningiomas. Molecular and translational advances in meningiomas. Neuro-Oncology. Volume 21, Issue Supplement_1, January 2019:i4-i17. doi: 10.1093/neuonc/noy178

Nassiri F, Price B, Shehab A et al. (2019) Life after surgical resection of a meningioma: a prospective cross-sectional study evaluating health-related quality of life. Neuro-Oncology. 2019 Jan 14;21(Supplement_1):i32-i43. doi: 10.1093/neuonc/noy152.

Huang RY, Bi WL, Griffith B, Kaufmann TJ et al.(2019) Imaging and diagnostic adavances for intracranial meningioma. Neuro-Oncology. 2019 Jan 14;21(Supplement_1):i44-i61. doi: 10.1093/neuonc/noy143

Brastianos PK, Galanis E, Butowski N et al. (2019) Advances in multidisciplinary therapy for meningiomas. Neuro-Oncology. 2019 Jan 14;21(Supplement_1):i18-i31. doi: 10.1093/neuonc/noy136

Emmanouil B, Houston R, May A, Ramsden JD, Hanemann CO, Halliday D, Parry A, Mackeith S (2018) Progression of hearing loss in Neurofibromatosis type 2 according to genetic severity. Laryngoscope. 2018 Nov 19 doi: 10.1002/lary.27586

Collord G, Tarpey P, Kurbatova N, Martincorena I, Moran S, Castro M, Nagy T, Bignell G, Maura F, Young MD, Berna J, Tubio JMC, McMurran CE, Young AMH, Sanders M, Noorani I, Price SJ, Watts C, Leipnitz E, Kirsch M, Schackert G, Pearson D, Devadass A, Ram Z, Collins VP, Allinson K, Jenkinson MD, Zakaria R, Syed K, Hanemann CO, Dunn J, McDermott MW, Kirollos RW, Vassiliou GS, Esteller M, Behjati S, Brazma A, Santarius T, McDermott U. (2018) An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures. Sci Rep. 2018 Sep 10;8(1):13537. doi: 10.1038/s41598-018-31659-0. 

Raghu SV, Mohammad F, Chua JY, Lam JSW, Loberas M, Sahani S, Barros CS, Claridge-Chang A. (2018) A zinc-finger fusion protein refines Gal4-defined neural circuits. Mol Brain. 2018 Aug 20;11(1):46. doi: 10.1186/s13041-018-0390-7. 

Button RW, Roberts SL, Willis TL, Hanemann CO, Luo S (2017) Accumulation of autophagosomes confers cytotoxicity. J Biol Chem. 2017 Aug 18;292(33):13599-13614. doi: 10.1074/jbc.M117.782276. 

Oon CE, Bridges E, Sheldon H, Sainson RCA, Jubb A, Turley H, Leek R, Buffa F, Harris AL, Li JL (2017) Role of Delta-like 4 in Jagged1-induced tumour angiogenesis and tumour growth. Oncotarget. 2017 Jun 20;8(25):40115-40131. doi: 10.18632/oncotarget.16969. 

Bassiri K, Ferluga S, Sharma V, Syed N, Adams CL, Lasonder E, Hanemann CO (2017) Global Proteome and Phospho-proteome Analysis of Merlin-deficient Meningioma and Schwannoma Identifies PDLIM2 as a Novel Therapeutic Target. EBioMedicine. 2017 Feb;16:76-86. doi: 10.1016/j.ebiom.2017.01.020.

Stepanova DS, Semenova G, Kuo YM, Andrews AJ, Ammoun S, Hanemann CO, Chernoff J. (2017). An Essential Role for the Tumour-Suppressor Merlin in Regulating Fatty Acid Synthesis. Cancer Res. 77(18):5026-5038. doi: 10.1158/0008-5472.CAN-16-2834.

Provenzano L, Ryan Y, Hilton DA, Lyons-Rimmer J, Dave F, Maze EA, Adams CL, Rigby-Jones R, Ammoun S & Hanemann CO (2017). Cellular prion protein (PrPC) in the development of Merlin-deficient tumours. Oncogene 36(44):6132-6142. doi:10.1038/onc.2017.200

Cooper J, Xu Q, Zhou L, Pavlovic M, Ojeda V, Moulick K, de Stanchina E, Poirier JT. Zauderer M, Rudin CM, Karajannis MA, Hanemann CO, Giancotti FG. (2017). Combined inhibition of NEDD8-activating enzyme and mTOR suppresses NF2 loss–driven tumorigenesis. Mol Cancer Ther 16(8):1693-1704. doi: 10.1158/1535-7163.MCT-16-0821 

Bassiri K, Ferluga S, Sharma V, Syed N, Adams CL, Lasonder E, Hanemann CO (2017). Global proteome and phospho-proteome analysis of Merlin-deficient meningioma and schwannoma Identifies PDLIM2 as a Novel Therapeutic Target. EBioMedicine. 2017 Feb;16:76-86.

Zhou L, Lyons-Rimmer J, Ammoun S, Müller J, Lasonder J, Sharma V, Ercolano E, Hilton D, Taiwo I, Barczyk M Hanemann CO (2016) The scaffold protein KSR1, a novel therapeutic target for the treatment of merlin deficient tumours, Oncogene, 35(26):3443-53. 

Schulz A, Buettner R, Hagel C, Baader SL, Kluwe L, Salamon J, Mautner VF, Mindos T, Parkinson DB, Gehlhausen JR, Clapp DW, Morrison H (2016) The importance of nerve microenvironment for schwannoma development, Acta Neuropathologica 132,(2), 289–307

Hanemann CO, Blakeley JO,  Nunes FP, Robertson K, Stemmer-Rachamimov A, Mautner V, Kurtz A, Ferguson M,  Widemann BC, Plotkin SR, Evans DG, Ferner R, Carroll SL, Korf B, Wolkenstein P, Knight P (2016).  Current status and recommendations for biomarkers in Neurofibromatosis 1, Neurofibromatosis 2 and schwannomatosis, Neurology, 87(7 Suppl 1):S40-8. 

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