Of all cancer types, tumours of the nervous system probably represent the most dreadful and difficult-to-treat. The incomplete understanding of tumour biology and the lack of effective diagnostic tools underlie the difficulties in treating these neoplasms. The central theme of his Programme has two major objectives: a) to study tumoursuppressive and metabolic pathways underlying growth control and transformation in neural progenitor/stem cells; b) to uncover ‘druggable’ metabolic pathways controlling invasiveness and resistance to therapy in tumour-initiating cells in brain cancers.

Our work has led to two key discoveries:

i) We revealed an unexpected role of the tumour suppressor Promyelocytic Leukaemia (PML) in suppressing proliferation of neural progenitor/stem cells in conjunction with the Retinoblastoma protein.

ii) We discovered that activation of the stereotypic/stress response pathway autophagy plays a central role in survival of cancer cells and tumour-initiating cells upon targeted

therapies. These findings revealed fundamental mechanisms underlying growth control at the level of both normal and cancerous progenitor/stem cells and also have potentially important translational ramifications. For instance, our work has led to an MRC-funded Phase II clinical trial for the use of autophagy inhibitors in conjunction with the tyrosine kinase inhibitor Imatinib.

My programme has strong collaborative interactions with the intramural programmes of UCL as well as with other leading laboratories, which bring relevant interdisciplinary expertise to this Programme, linking basic and clinical research. My Programme is also linked to the UCL Centre for Stem Cells and Regenerative Medicine and UCL Neuroscience.