Featured Publications
Titration of RAS alters senescent state and influences tumour initiation
Chan A, Zhu H, Narita M, Cassidy L, Young A, Bermejo-Rodriguez C, Janowska A, Chen H, Gough S, Oshimori N, Zender L, Aitken S, Hoare M, Narita M. Titration of RAS alters senescent state and influences tumour initiation. Nature 2024, 633: 678-685. PMID: 39112713, PMCID: PMC11410659, DOI: 10.1038/s41586-024-07797-z.Peer-Reviewed Original ResearchConceptsTumor typesOncogenic RAS-induced senescenceInfluence tumor initiationProgenitor-like featuresTumor-initiating phenotypeSingle-cell RNA sequencing analysisModel in vivoHCC subclassesModel in vitroHepatocellular carcinomaTumor suppressor mechanismEarly tumorigenesisTumor initiationEarly-onsetProgenitor featuresInduce tumorsSuppressor mechanismTumorLate-onsetRNA sequencing analysisOncogenic stressRas-induced senescenceIn vivoMolecular signaturesOncogene dosageConvergent somatic mutations in metabolism genes in chronic liver disease
Ng S, Rouhani F, Brunner S, Brzozowska N, Aitken S, Yang M, Abascal F, Moore L, Nikitopoulou E, Chappell L, Leongamornlert D, Ivovic A, Robinson P, Butler T, Sanders M, Williams N, Coorens T, Teague J, Raine K, Butler A, Hooks Y, Wilson B, Birtchnell N, Naylor H, Davies S, Stratton M, Martincorena I, Rahbari R, Frezza C, Hoare M, Campbell P. Convergent somatic mutations in metabolism genes in chronic liver disease. Nature 2021, 598: 473-478. PMID: 34646017, DOI: 10.1038/s41586-021-03974-6.Peer-Reviewed Original ResearchConceptsSomatic mutationsConvergent evolutionNon-alcoholic fatty liver diseaseMetabolic genesAlcohol-related liver diseaseFatty liver diseaseFrequent convergent evolutionRegulation of metabolic pathwaysLiver diseaseExcess of mutationsLipid droplet metabolismHepatocellular carcinomaBurden of somatic mutationsStorage triacylglycerolsAcquisition of somatic mutationsNuclear exportIndependent clonesChronic liver diseases to hepatocellular carcinomaIncreased clone sizePositive selectionMaster regulatorsTranscription factorsInsulin signalingChronic liver diseaseMetabolic pathwaysSomatic mutations and clonal dynamics in healthy and cirrhotic human liver
Brunner S, Roberts N, Wylie L, Moore L, Aitken S, Davies S, Sanders M, Ellis P, Alder C, Hooks Y, Abascal F, Stratton M, Martincorena I, Hoare M, Campbell P. Somatic mutations and clonal dynamics in healthy and cirrhotic human liver. Nature 2019, 574: 538-542. PMID: 31645727, PMCID: PMC6837891, DOI: 10.1038/s41586-019-1670-9.Peer-Reviewed Original ResearchConceptsChronic liver diseaseHepatocellular carcinomaLiver diseaseCirrhotic liverMutational burdenSomatic mutationsMutational signaturesProgression to chronic liver diseaseSynchronous hepatocellular carcinomaNon-malignant hepatocytesExcessive alcohol intakeComplexity of hepatocellular carcinomaBands of fibrosisNon-alcoholic fatty liver diseaseStructural variantsFatty liver diseaseGenome of hepatocellular carcinomaClinical spectrumAlcohol intakeLiver failureViral hepatitisClonal expansionMalignant transformationHealth to diseaseRegenerative nodulesMutational landscape of a chemically-induced mouse model of liver cancer
Connor F, Rayner T, Aitken S, Feig C, Lukk M, Santoyo-Lopez J, Odom D. Mutational landscape of a chemically-induced mouse model of liver cancer. Journal Of Hepatology 2018, 69: 840-850. PMID: 29958939, PMCID: PMC6142872, DOI: 10.1016/j.jhep.2018.06.009.Peer-Reviewed Original ResearchConceptsSomatic single nucleotide variantsCarcinogen-induced mouse modelsModel of hepatocellular carcinomaMouse model of liver cancerMutational landscape of tumorsModel of liver cancerLandscape of tumorsHepatocellular carcinomaMouse modelMutational landscapeLiver cancerOncogenic drivers of HCCLiver tumorsNon-synonymous point mutationsGenomic alterationsHuman diseasesTruncating mutations of APCMutational signaturesMouse model of hepatocellular carcinomaSingle nucleotide variantsDrivers of hepatocellular carcinomaChemically-induced mouse modelCopy number alterationsCOSMIC mutational signaturesActivating hotspot mutations
2024
Novel immunotherapeutics against LGR5 to target multiple cancer types
Chen H, Mueller N, Stott K, Kapeni C, Rivers E, Sauer C, Beke F, Walsh S, Ashman N, O’Brien L, Rafati Fard A, Ghodsinia A, Li C, Joud F, Giger O, Zlobec I, Olan I, Aitken S, Hoare M, Mair R, Serrao E, Brenton J, Garcia-Gimenez A, Richardson S, Huntly B, Spring D, Skjoedt M, Skjødt K, de la Roche M, de la Roche M. Novel immunotherapeutics against LGR5 to target multiple cancer types. EMBO Molecular Medicine 2024, 16: 2233-2261. PMID: 39169164, PMCID: PMC11393416, DOI: 10.1038/s44321-024-00121-2.Peer-Reviewed Original ResearchConceptsHepatocellular carcinomaColorectal cancerTarget multiple cancer typesBispecific T-cell engagerCell killing in vitroChimeric antigen receptorT-cell engagersCancer cells in vitroPre-B-ALLAnti-tumor efficacyCancer cell killing in vitroKilling in vitroCells in vitroAntibody-drug conjugatesMultiple cancer typesLgr5 overexpressionTumor burdenAntigen receptorMurine modelNovel immunotherapeuticsCancer modelsTumor cellsEffective modalityEffective tumorLgr5
2020
P37 Convergent somatic mutations in effectors of insulin signalling in chronic liver disease
Ng S, Brunner S, Brzozowska N, Aitken S, Abascal F, Moore L, Leongamornlert D, Ivovic A, Robinson P, Butler T, Sanders M, Williams N, Coorens T, Teague J, Raine K, Butler A, Hooks Y, Wilson B, Birtchnell N, Naylor H, Davies S, Stratton M, Martincorena I, Hoare M, Campbell P. P37 Convergent somatic mutations in effectors of insulin signalling in chronic liver disease. Gut 2020, 69: a25-a25. DOI: 10.1136/gutjnl-2020-basl.47.Peer-Reviewed Original ResearchChronic liver diseaseLiver diseaseSomatic mutationsAssociated with metabolic dysregulationSystemic metabolic dysfunctionNon-alcoholic fatty liver diseaseFatty liver diseaseInsulin signalingEffectors of insulin signalingLiver failureHepatocellular carcinomaMultiple independent acquisitionsGram of tissueDownstream of insulin signalingMetabolic dysfunctionMetabolic dysregulationNormal controlsPatient samplesLiver samplesExcess of mutationsNormal liverDietary caloriesLiverAlcohol-relatedDisease
2011
Accuracy of hepatocellular carcinoma detection on multidetector CT in a transplant liver population with explant liver correlation
Addley H, Griffin N, Shaw A, Mannelli L, Parker R, Aitken S, Wood H, Davies S, Alexander G, Lomas D. Accuracy of hepatocellular carcinoma detection on multidetector CT in a transplant liver population with explant liver correlation. Clinical Radiology 2011, 66: 349-356. PMID: 21295772, DOI: 10.1016/j.crad.2010.11.012.Peer-Reviewed Original ResearchConceptsDetection of HCC lesionsMultidetector computed tomographyHepatocellular carcinomaMDCT examinationsHCC lesionsLiver transplantationDiagnostic confidenceDiagnostic accuracyDiagnostic accuracy of multidetector computed tomographyAccuracy of multidetector computed tomographySize of hepatocellular carcinomaLesion sizeDetection of hepatocellular carcinomaFive-point confidence scaleHepatocellular carcinoma detectionHelical CT imagesEffect of radiologist experienceLiver populationMultidetector CTCirrhotic patientsHistopathological correlationHistopathological resultsComputed tomographyCarcinoma detectionRadiologist experience