Understanding the biology of brain tumours

Using models in in vitro and in vivo systems to understand the genetics and signalling that drive brain tumour initiation and growth
Fruit fly brain model with orange colouration

Understanding the biology of brain tumours

Using models in in vitro and in vivo systems to understand the genetics and signalling that drive brain tumour initiation and growth
Title: Understanding the biology of brain tumours
Dates: Ongoing
University of Plymouth PI: Professor David Parkinson 
 
This study aims to use models in in vitro and in vivo systems to understand the genetics and signalling that drive initiation and growth in meningioma, schwannoma and glioma brain tumours.
The biology of schwannoma, meningioma and glioma tumours is a main focus of the work at the Plymouth Brain Tumour Centre. The Parkinson lab, together with the labs of Claudia Barros, Sylwia Ammoun, Claire Adams, Leandro Jose De Assis and Juri Na are working to understand the genetics of these. 
Work in this project involves the use of human tumour tissue, using both 2D and 3D culture systems, as well as in vivo Drosophila (fruit fly) genetic models and pre-clinical mouse models.

An important part of the work done by the Brain Tumour Research Centre is to understand the changes in brain tumours that drive the cell de-differentiation from their quiescent state to begin to grow abnormally. Once we understand this, we can design therapies to block growth and eliminate the tumours.

David ParkinsonProfessor David Parkinson
Professor of Neuroscience and Director of BTRC

 
 
 

Examples of work within this project

Dr Leandro Jose de Assis and his team are leading a study to understand how aggressive meningiomas rewire metabolism. A key protein, hexokinase II (HK2), helps fuel this process. 
This work investigates ways to block HK2 and its partners, which could slow tumour growth by cutting off its energy supply specifically in tumour cells, reducing side effects on non-tumour cells.
Dr Sylwia Ammoun and her team, in collaboration with Dr Juri Na, are investigating the mechanisms by which tumour cells develop ways to withstand drug and radiation treatments. Dr Ammoun is also exploring the role of tumour-supporting immune cells in contributing to drug resistance, in collaboration with Dr Leandro Jose De Assis and Dr Claire Adams. 
Targeting multi-drug resistance in schwannoma and meningioma tumours is a novel approach and may improve treatment for patients with both sporadic and hereditary NF2-related tumours.
Professor David Parkinson and Dr Liyam Laraba are using in vitro and in vivo systems to understand the genetics of meningioma and schwannoma tumours. 
They are interested in what events initiate schwannoma formation and how the blood supply to tumour tissue may change and develop during tumour formation.
Dr Claudia Barros and her team, with Dr Jon Gil-Ranedo, explore novel mechanisms by which brain tumour initiating cells lead to and sustain glioma growth, and may also play a role in the transition of low grade to more aggressive glioma tumours. The group also investigates glioma stem cell plasticity, including quiescence, a state when glioma initiation cells can escape conventional therapies. 
Their work aims to better understand and expose novel ways to stop glioma growth.
Dr Mahmoud Labib's team investigates targetable molecules responsible for release of cytokine and chemokines, such as IL-6 in glioblastoma and CSF-1 in meningioma, which can help tumours grow and hide from immune system attack. 
For this, they use a proprietary, innovative, high-throughput microfluidic method called Secretion-Enabled Cell Ranking and Enrichment Technique (SECRET) and combine it with functional CRISPR approaches. By switching off or blocking these molecule regulators, they hope to develop new treatments for glioblastoma and meningioma. They have also developed a microfluidic platform to isolate rare circulating tumour cells from non-small cell lung cancer patients with brain metastases and are working to identify gene signatures associated with brain metastasis.
Dr Ming Li's team focuses on guanylate-binding proteins (GBPs), a family of proteins that normally play a key role in the body's immune defence against infection. 
The team works to uncover molecular mechanisms underlying GBPs' roles in promoting tumour progression by supporting glioma-initiating cells and suppressing anti-tumour immune responses. They aim at developing new therapies targetting GBPs in glioma, including astrocytoma and glioblastoma, and in lower-grade tumours such as meningioma and schwannoma.

Brain Tumour Research Centre

The internationally renowned Brain Tumour Research Centre (BTRC) focuses on low-grade tumours and investigates new mechanisms underlying brain tumourigenesis, including tumour initiation. 
We work truly from bedside to bench and back. We have a large biobank of stratified tumour samples and are using a variety of complementary tumour models. The BTRC encompasses research groups working closely together and complementing each other with both shared approaches and shared in vitro and in vivo models.
 
Glioma stem cells with bright colouration