Metabolic analysis of the tumour suppressor protein p73 in medulloblastoma

12 September 2014
Dr Maria Victoria Niklison-Chirou

Dr Maria Victoria Niklison-Chirou, Blizard Institute, Centre for Neuroscience and Trauma, Queen Mary University of London

Medulloblastoma (MB) is the most common malignant brain tumour in children. Current treatments include surgery and radio/chemotherapy which can cause significant side effects including neurological, intellectual and physical disabilities.  

The main purpose of this research project is to develop a new treatment for children with medulloblastoma, by studying the protein p73.

p73 plays a central role in the development of the central nervous system and in metabolism. Metabolic adaptation has emerged as a hallmark of cancer and as a promising therapeutic target. The main purpose of this project is to study the metabolic adaptation of medulloblastoma tumours with the final goal to understand whether p73 or its downstream targets could be developed as a novel therapeutic target for these tumours.

Amount of grant: £378,965 | Date of award: May 2014

Overview

Brain tumours are the leading cause of childhood cancer death.

Medulloblastoma is the most common malignant paediatric brain tumour with a five-year survival rate of 60-70%. Current treatments include surgery, radio and chemotherapy, which are associated with significant side effects such as neurological, intellectual and physical disabilities. More targeted and less toxic therapies are vitally needed to improve the quality of life of survivors.

Metabolic adaptation has emerged as a hallmark of cancer and as a promising therapeutic target. Rapidly growing cancer cells adapt their metabolism by increasing nutrient uptake and energy production.

The p53 protein is a “tumor suppressor gene” i.e. its activity stops the formation of tumours. A p53-family member, the protein p73 plays a key role in the development of the central nervous system and in the regulation of metabolism by directly influencing various metabolic pathways.

Dr Niklison-Chirou will study the involvement of p73 in medulloblastoma and in particular its role in metabolic adaptation of these tumours. The final goal is to understand whether p73 or its downstream targets could be developed as a novel therapeutic targets for these tumours.

Read more: About medulloblastoma

About the research team

Dr Niklison-Chirou will carry out her research in the Blizard Institute at Barts and The London School of Medicine, Queen Mary University of London, a highly dynamic and international research environment. Dr Niklison-Chirou has expertise in molecular mechanisms of cancer metabolism combined with the unique pre-clinical and translational brain tumour knowledge at the Blizard Institute.

Dr Niklison-Chirou will be interacting with Silvia Marino, a world-renowned expert in epigenetic regulation in brain tumours with expertise in translational neuro-oncology research. She has also established essential collaborations with Dr Marc Remke, Prof. Steve Clifford and Dr Tom Jacques for access to DNA dataset and RNASeq dataset on human MB and MB primary cells respectively.

What difference will this project make?

Brain tumours are the leading cause of childhood cancer death. There is a desperate need for new therapies.
 
p73 plays an important role in the development of the central nervous system, however its involvement in the development of medulloblastoma has not been investigated in detail.

Recent discoveries have highlighted the role of p73 in cell metabolism. Dr Niklison-Chirou will test the hypothesis that p73-regulated cell metabolism is essential for a medulloblastoma cell to survive under stress conditions.

Deciphering the processes underlying p73-driven metabolic adaptation in medulloblastoma cells has the potential to uncover key factors allowing cancer cells to adapt and survive under metabolic stresses, such as low oxygen environment and nutrient starvation. These key factors will lay the basis for the discovery of new biomarkers for drug targeting.

Read more: About childhood brain tumours | Other brain tumour research | Brain tumour initiative

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