Research Interest

Novel disease models of paediatric high grade glioma

Progress in the evaluation of novel targeted therapies and mechanisms of molecular pathogenesis have been limited in paediatric high grade glioma in part due to the lack of model systems specifically representing the childhood disease. Most data has been extrapolated from a small series of adult glioblastoma cell lines grown as monolayers in vitro, and implanted subcutaneously in vivo, which are poorly predictive of the clinical efficacy of a compound, and do not reflect the specific genomic alterations found in the childhood setting.

We are attempting to address this paucity by developing and characterising novel models of paediatric high grade glioma for preclinical screening and functional assays. As a first step, we have collected a series of immortalised cell lines derived from childhood gliomas, and performed detail molecular and phenotypic profiling prior to incorporation into specific preclinical studies. We have also undertaken to xenograft these lines, generating unique luciferase-labelled sublines capable of tumour formation both subcutaneously and intracranially (collaboration with Dr Suzanne Eccles, Division of Cancer Therapeutics and  Dr Simon Robinson, CRUK/ESPRC Cancer Imaging Centre ICR).

Ongoing work is aimed at producing a diverse collection of primary neurospheres which represent the clinical heterogeneity observed in the paediatric high grade glioma genome. These three-dimension cultures are enriched for tumour progenitor populations, and are thought to better reflect the gene expression patterns present in the human disease. In addition we are working with Dr Lou Chesler, Division of Cancer Studies, to generate novel genetically engineered mouse models of paediatric high grade glioma based upon the specific genetic alterations we have reported to be driving the disease.

Selected recent publications

1. Perryman L, Box G, Boult J, Marshall L, Popov S, Jury SA, Pearson ADJ, Workman P, Hargrave D, Robinson S, Jones C, and Eccles SA (in preparation) “Development and characterisation of in vivo models of paediatric high grade glioma“

2. Bax DA*, Little SE,* Gaspar N, Perryman L, Marshall L, Viana-Pereira M, Jones TA, Williams RD, Vassal G, Workman P, Sheer D,  Reis RM, Pearson ADJ,  Hargrave D and Jones C (2009) “Molecular and phenotypic characterisation of paediatric high grade glioma cell lines as models for preclinical drug development” PLoS ONE 4:e5209