My research program aims to understand the role of cellular senescence in paediatric brain and pituitary tumours and reveal novel therapies against these neoplasias. Paediatric cancers are embryonic defects and as such, we believe that they need to be studied within the context of a developing embryo. My lab combines developmental, molecular and cellular approaches to study high- and low-grade gliomas in children as well as craniopharyngioma, the most common childhood pituitary tumour. We have developed mouse models of paediatric tumours and performed detailed ‘omics ‘ studies in human and mouse tumours. These approaches have provided important insights into normal brain and pituitary development in the last years (e.g. Haston et al., Development 2017; Carreno et al., Development 2017). In addition, we have contributed significantly to the understanding of the aetiology and pathogenesis of human congenital hypopituitarism and paediatric craniopharyngioma (Gaston et al., PNAS 2011; Andoniadou et al., Acta Neuropathol. 2012; Andoniadou et al., Cell Stem Cell 2013). We have revealed that cellular senescence through its secretome drives cell transformation and tumour initiation in the context of craniopharyngioma and that the senescent cells are sensitive to senolytics (Gonzalez-Meljem et al., Nat. Commun. 2017; Guerrero et al., Nat. Metabolism 2019).  We have performed transcriptomic analysis in human samples to identify targetable pathways, and propelled these findings into a clinical trial (Apps et al., Acta Neuropathol. 2018).

More recently, we have expanded our research to other paediatric brain tumours. For instance, using an in vitro model, we have shown that pilocytic astrocytoma, the most frequent brain tumour in children, is sensitive to senolytics (i.e. compounds that selectively kill senescent cells) (Buhl et al., Clinical Cancer Research 2019). Likewise, we are studying models of high-grade glioma to reveal novel vulnerabilities and assess the potential use of senolytics in combination with standard therapies.