Section of Molecular Oncology
Led by Professor Maggie Knowles
We aim to translate knowledge of cancer biology into clinical practice with the goal of improving patient management and outcomes. Our studies use a range of technologies including genomics, structural and computational biology, in vitro and in vivo functional models and microfluidics technology, to identify and validate clinically informative biomarkers and therapeutic targets and develop novel therapeutic approaches.
Maggie Knowless group uses genomics technologies to study bladder cancer. This work is underpinned by an extensive collection of clinical samples. Specific aims are to improve tumour sub-classification at diagnosis and to identify prognostic and predictive biomarkers and therapeutic targets. The group carries out functional studies on genes of critical importance in bladder cancer development, including FGF receptors and chromatin modifier genes using normal human urothelial cells and a panel of extensively characterised bladder tumour cell lines.
Richard Bayliss studies the molecular structures and interactions of proteins using structural, cell, chemical and computational biology approaches. He works towards understanding the molecular mechanisms that underpin cell division and cancer signalling pathways to develop precision drugs that are tailored to individual proteins. Recent studies have examined the allosteric mechanism by which the non-catalytic, C-terminal domain of NEK9 activates NEK7 and showed that IRE1 is regulated through a similar mechanism. Lung cancer patients who harbor EML4-ALK fusions initially respond to ALK inhibitors such as crizotinib, but inevitably relapse. The contribution of the EML4 part of the fusion is under investigation as a target for therapeutics. The structure of the TAPE domain of the related protein EML has been determined, providing a molecular basis for the sensitivity of EML4-ALK fusions to Hsp90 inhibition.
Sue Burchills group studies metastatic drug resistant disease responsible for progression and relapse in children and young people with neuroblastoma and bone cancer. Through studying tumour and tumour-derived tissues and cells the group has developed novel preclinical models, to identify more personalised responsive methods to manage and treat patients to improve outcomes. The group are leading circulating biomarker research in current international clinical trials for neuroblastoma (HR-NBL-1.5/SIOPEN, BEACON) and Ewings sarcoma (Euro Ewing 2012, rEECur).
Mihaela Lorgers group focuses on the tumour microenvironment in brain metastases. In addition to investigating the cross-talk between cancer and inflammatory cells in the brain, they are exploiting strategies for the inhibition of brain metastases through immunomodulatory approaches, foremost the delivery of immunomodulatory factors within the progeny of hematopoietic stem cells that naturally home to brain metastases and immune checkpoint inhibition.
Natalia Riobo del Galdo studies the molecular mechanisms that mediate and regulate the Hedgehog signalling pathway in normal and cancer cells. One aspect is aimed at learning how Hedgehog binding to its receptor in the primary cilium sets in motion the entire signalling cascade and to develop novel therapeutic interventions that will inhibit that step. Another aspect is the study of the effect of non-transcriptional effects of Hedgehog, collectively called non-canonical, in epithelial cancer progression and maintenance and their crosstalk with other oncogenic signals.
All academic staff in the Section contribute to teaching in their specialist areas, including the teaching of medical students and undergraduate and postgraduate life sciences students.
Dr Natalia Riobo del Galdo
Hedgehog Research Group
Dr Sally Peyman
Microfluidics and Oncology-on-chip Group