When: Wednesday, May 11, 2022, 12:00 PM - 1:30 PMWhere: Clark-Kennedy Lecture Theatre, Queen Mary Innovation Centre, Whitechapel
Speaker: Dr Tom Bird, Honorary Consultant Hepatologist and Reader at Edinburgh University
Speaker: Dr Tom Bird, Honorary Consultant Hepatologist and Reader at Edinburgh University and Senior Lecturer at the CRUK Beatson Institute in GlasgowTitle: Towards precision medicine and targeted prevention in Hepatocellular Carcinoma
The first session of our Institute Research Seminar Series will take place on Wednesday 11 May 2022, 12.00–1.30pm, at the Clark-Kennedy Lecture Theatre, Queen Mary Innovation Centre.
Dr Tom Bird, Honorary Consultant Hepatologist and Reader at Edinburgh University and Senior Lecturer at the CRUK Beatson Institute in Glasgow, will present “Towards precision medicine and targeted prevention in Hepatocellular Carcinoma”.
As liver disease and cancer becomes increasingly prevalent we need to accelerate translational research towards improving outcomes for patients and catch up with the step changes established for other cancers. Using a combination of human tissue and advanced preclinical mouse model systems our group has studied aberrant hepatocellular regeneration, malignant transformation and hepatocellular carcinoma (HCC) tumour evolution. Exploring why, despite a large functional mass of potentially regenerative hepatocytes, we described senescence as a key driver in preventing pathophysiological liver regeneration which also drives multisystem organ dysfunction. Senescent responses are also activated following oncogenic transformation of hepatocytes. This phenotype is targetable for specific tumour subtypes during early HCC carcinogenesis, leading to reduced tumour incidence and prolonged survival, through the depletion of early tumour clones. With the development of a range of bespoke genetically engineered mouse models, tailored to human relevant combinations of oncogenes/tumour suppressors, we validate a suite of models against the breadth of human HCC. Using these models coupled to downstream organoid and orthotopic transplantation systems we are able to rapidly identify subtype specific therapeutic combinations through high throughput screening technology. These novel therapeutic combinations are highly effective when validated in vivo showing proof of principle for this immunocompetent model platform to provide a foundation for precision medicine in HCC.
Tom Bird is an Honorary Consultant Hepatologist and Reader at Edinburgh University and Senior Lecturer at the CRUK Beatson Institute in Glasgow. His clinical practice expertise is in HCC and this work is based at Edinburgh’s Royal Infirmary in close collaboration with the Scottish Liver Transplant Unit. He studied physiological sciences and medicine at Oxford working in vaccine immunology and infectious diseases. Having discovered a passion for clinical hepatology he gained a PhD studying liver regeneration in 2011. He has gone on, in collaboration with others, to describe how liver stem cells regenerate the liver and how they could be manipulated therapeutically. This has led to work on the role of senescence in impairing liver regeneration in the acute setting, whilst promoting cancer and multisystem organ dysfunction chronically. His work now focuses on liver cancer subtypes and how genetically engineered mouse models (GEMMs) may be used for precision medicine. Studying these GEMMs, his group wishes to understand early dynamics of tumour clone establishment and identify targets for treating late stage tumours. Through the description of neutrophil reprogramming in related model systems he and others have recently established the CUBIC clinical trial testing combination CXCR2 antagonism with immunotherapy in a phase 1b/2 trial in collaboration with AstraZeneca. His pre-clinical research has been recognised by the award of a number of national and international prizes and Fellowships. He leads a work package for the HUNTER HCC European Consortium, leads the HCC component of the CRUK Scottish Centre and sits on the faculty of the CRUK Beatson Institute.