Tumour Progression

The primary research interests of our Lab are the mechanisms driving inter- and intra-tumoural heterogeneity and the implications for neoplastic progression, metastasis and therapeutic response. We have focused on gene regulation by transcriptional networks and microRNAs, with a disease focus on breast and prostate carcinoma and the childhood cancer neuroblastoma. The Lab combines fundamental discovery techniques including single cell transcriptomics, proteomics and ChIP-Seq with genome-scale functional genomics to deconvolute transcriptional heterogeneity and functionally annotate regulatory networks in malignancy.

We also have a strong track record in the discovery, development and preclinical validation of novel therapeutic targets and molecular biomarkers, using ‘state of the art’ transgenic models and patient-derived xenografts in collaboration with clinical partners. Collectively, the Lab has expertise in cell and molecular biology, bioinformatics and translational and medical oncology. Our lab was the first to discover a microRNA targeting p53 and to demonstrate therapeutic benefit from systemic delivery of a drug-like microRNA inhibitor in vivo. We were also the first to demonstrate paracrine Hedgehog signalling in breast cancer and are now testing the efficacy of hedgehog pathway drugs as novel therapeutics for high-risk breast cancers. We have recently discovered a central role for the transcription factor Id4 in breast stem cell homeostasis and the aetiology of basal breast cancer.

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