Characterization of molecular and cellular mechanisms implicated in evasion of anti-VEGF therapies by human brain tumours

Angiogenesis is a biological process by which new capillaries are formed from pre-existing vessels. It is well established that brain tumour growth depends on angiogenesis. Anti-angiogenic therapies directed against the tumour vasculature should deprive the tumour of oxygen and nutrients and therefore represent a powerful adjuvant to traditional therapy. Therapeutic approaches aimed to avoid the binding of pro-angiogenic factor VEGF to its receptor have therefore attracted considerable attention. However, although current anti-VEGF therapies lead to an initial reduction in the size of the tumour, this progression free period is transient and inevitably followed by a second phase of massive regrowth. Recent findings indicate that anti-VEGF evasion is associated to revascularisation of the tumour and to a strong increase in the invasiveness of the tumoral cells, but the molecules implicated in this process are not known yet.

This project aims to identify molecular targets implicated in anti-VEGF evasion in glioblastoma patients.

The PhD project will involve in vitro culture of glioblastoma cells derived from patients. These cultures will be characterised using molecular and cellular biology techniques including qPCR, western blot and immunofluorescence confocal microscopy. The response of patient-derived cells to anti-VEGF treatments will be analysed using cutting-edge -omics approaches, such as RNA-seq and proteomics.

The successful candidate will be extensively trained in these techniques as well as in improving presentation skills by participating in weekly laboratory meetings, internal student seminar series and presenting data in relevant conferences in the field. 

For further information regarding the project or an informal discussion please contact Director of Studies, Prof Angel Armesilla   a.armesilla@wlv.ac.uk