Teams

Glasgow, UK

Prof Owen Sansom

Director
CRUK Scotland Institute
Glasgow
Owen Sansom email: o.sansom@beatson.gla.ac.uk

Website link: Prof Owen Sansom

In a research career spanning more than 20 years, Professor Sansom has published over 300 papers and made major contributions to understanding some of the key molecular drivers of epithelial cancer.

Professor Sansom received his PhD from the University of Edinburgh in 2001 before continuing his postdoctoral research using in vivo models of cancer at the University of Cardiff. In 2005, he established his own laboratory at the Cancer Research UK Beatson Institute in Glasgow. Since then, Professor Sansom has been instrumental in determining the molecular hallmarks of colorectal cancer. This has included defining the roles of the tumour suppressor protein APC and the WNT signalling pathway as well as the involvement of intestinal stem cells in tumourigenesis. His laboratory uses both in vivo and 3D in vitro models to recapitulate colorectal and pancreatic cancers to investigate the molecular mechanisms underpinning tumourigenesis and to identify novel drug targets.

Professor Sansom has also played an important leadership and management role at the CRUK Scotland Institute (formerly the Beatson Institute), particularly in ensuring its researchers are able to access the most sophisticated genetically engineered models of cancer. In 2011, he was appointed Deputy Director of the Institute and has been its Director since August 2017. Professor Sansom is also more broadly involved in driving cancer research strategy in Glasgow – up until April 2021, he was Director of the Institute of Cancer Sciences, University of Glasgow and currently is the Co-Director of the CRUK Scotland Centre, a joint initiative between Edinburgh and Glasgow, which aims to translate findings from the laboratory into the clinic for the benefit of cancer patients. In September 2021, Professor Sansom was appointed Director of the National Mouse Genetics Network, an investment of more than £20 million by the Medical Research Council to accelerate our understanding of human disease, including cancer, and improve diagnosis and treatments.

People involved:

Andrew Campbell	Research Team Leader
Fiona Paulin-Ali	Project coordinator
Tamsin Lannagan	Principal Scientific Officer
Rachel Ridgway	Principal Scientific Officer
Noha Mohammed	Postdoctoral Researcher
Michael Gillespie	PhD student/clinical fellow
Mark White	PhD student/clinical fellow
Megan Mills	Senior Scientific Officer
Abdullah Alyamani	Research Fellow
Richard Wilson	Consultant Medical Oncologist
Janet Graham	Consultant Medical Oncologist

Edinburgh, UK

Prof Ian Tomlinson

Charles and Ethel Barr Chair of Cancer Research
Edinburgh Cancer Research
Institute of Genetics and Cancer
The University of Edinburgh
Ian Tomlinson email: Ian.Tomlinson@ed.ac.uk

Website link: Ian Tomlinson | The University of Edinburgh

 

Prof Malcolm Dunlop

Colon Cancer Genetics Group and Academic Coloproctology
Edinburgh Cancer Research
Institute of Genetics and Cancer
The University of Edinburgh
Malcolm Dunlop email: malcolm.dunlop@ed.ac.uk

Website link: Malcolm Dunlop | The University of Edinburgh

Belfast, UK

Dr Philip Dunne

Senior Lecturer in Molecular Pathology
The Patrick G Johnston Centre for Cancer Research
Queen's University Belfast
Philip Dunne email: p.dunne@qub.ac.uk

Website link: Home - (dunne-lab.com)

Dr Philip Dunne is a Reader in Molecular Pathology, in the Patrick G Johnston Centre for Cancer Research at Queen’s University Belfast. His translational research programme primarily focusses in the identification, mechanistic interrogation and therapeutic targeting of the biology (particularly tumour-immune-stromal interactions) underpinning disease relapse in early-stage colorectal cancer. If we are to maximise patient benefits from the extensive pre-clinical research focussed on CRC in the UK, we must ensure that treatments are delivered to the right patients with tumour types that are fully aligned to the pre-clinical models that have demonstrated the most benefit. The Dunne lab research programme has enabled the development of a number of novel resources to align biomarkers to patient data and the most appropriate model(s), which may help in improving the translation of mechanistic science into clinical trials.

We have seen a revolution in the development of cell- and animal-based models, coupled with rapid advances in the technologies being used for molecular, proteomic and histological profiling of tumour samples. The Dunne group utilises cross-disciplinary methodologies for biological discovery and identification of molecular signalling and/or phenotypes that will enable improved understanding of disease and translation of potential therapeutic options. The expertise required to perform, analyse and interpreted these new data now extends well beyond the field of biology and medicine, into new disciplines that will require translational and clinical research teams to establishment new collaborations.

This includes the development of a number of novel resources to align biomarkers to patient data and the most appropriate model(s). These research developments has enabled basic and mechanistic biologists to utilise the clinical and pre-clinical samples for downstream interrogation of the biology underpinning specific disease subtypes. A major barrier to more widespread alignment of human and mouse is inconsistencies in data analysis. To ensure that the wider research field can benefit from state-of-the-art disease-positioning developments from my research programmes, we have developed a freely-available human-mouse computational conversion application (MouS^R: https://mousr.qub.ac.uk/) that streamlines transcriptional characterization between species for non-computational users. Furthermore, we continue to develop easy-to-use tool that enable users to interrogate the cellular source of their gene/signatures of interest, using an array of tissue processing methodologies (ConfoundR: https://confoundr.qub.ac.uk/).

Link to MouS^R - human-mouse computational conversion application: https://mousr.qub.ac.uk/

Link to ConfoundR - interrogation of the cellular source of gene/signatures of interest: https://confoundr.qub.ac.uk/

People involved:

Raheleh Amirkhah	Research Fellow
Baharak Ahmaderaghi	Lecturer
Sudhir Malla	Post-doc
Shania Corry	PhD student

Manchester, UK

Prof Caroline Dive

Interim Director
Cancer Research UK Manchester Centre
The University of Manchester
Caroline Dive email: caroline.dive@cruk.manchester.ac.uk

Website link: Professor Caroline Dive | Cancer Research UK 

Upon completing her PhD studies in Cambridge, Professor Caroline Dive moved to Aston University’s School of Pharmaceutical Sciences in Birmingham where she established her own group studying mechanisms of drug induced tumour cell death, before moving to The University of Manchester to continue this research. Currently, she is Interim Director of the Institute and Director of its Cancer Biomarker Centre, with research spanning tumour biology, biomarker discovery and preclinical pharmacology alongside regulated laboratories for biomarker assay validation and qualification within clinical trials to Good Clinical Practice standards supporting clinical decision-making. 

Dr Natalie Cook

Clinical Snr Lecturer in Exp Cancer Med
Cancer Research UK Manchester Centre
The University of Manchester
Natalie Cook email: natalie.cook17@nhs.net

Website link: Dr Natalie Cook

Dr Natalie Cook is a Senior Clinical Lecturer in Experimental Cancer Medicine at The Christie NHS Foundation Trust/Division of Cancer Sciences, University of Manchester. She is also the clinical lead for Manchester Experimental Cancer Medicine Centre. She previously trained in Medical Oncology in Cambridge, UK, where she completed a PhD, funded by a CRUK Clinical Training fellowship.

Oxford, UK

Prof Tim Maughan

Professor of Clinical Oncology
University of Oxford
Tim Maughan email: tim.maughan@oncology.ox.ac.uk

Website link: https://www.oncology.ox.ac.uk/team/tim-maughan

Tim Maughan is Professor of Clinical Oncology at the University of Oxford. He has led large scale clinical trials in colorectal cancer in the UK (CR06, COIN, FOCUS3, FOCUS4).  His research interests are in applying the deepening understanding of colorectal cancer biology to clinical trials and exploitation of targeting the tumour microenvironment, notably the stromal cell compartment for therapeutic gain in high stromal colorectal cancer. As CI of the MRC stratified medicine consortium in colorectal cancer (S:CORT). Tim brings this dataset of clinical, molecular and imaging data from 2000 colorectal cancer patients for collaborative academic access to the ACRCelerate consortium. This resource is also available for commercial access via Cancer Research-UK on application.

Link to SCORT home page: https://www.s-cort.org/

Link to the Oxford SCORT page: https:/www.cancer.ox.ac.uk/research/networks/scort

People involved:

Enric Domingo	Post-doc
Callum Beech	D Phil student
Cristiano Peron	D Phil student
Helen Tyrrell	D Phil student
Ruby Wood	D Phil student

 

Prof Simon Leedham

Wellcome Senior Research Fellow in Clinical Science and Honorary Consultant Gastroenterologist
University of Oxford
Simon Leedham email: simon.leedham@well.ox.ac.uk

Website link: https://www.well.ox.ac.uk/people/simon-leedham

Simon Leedham is a Professor of Molecular and Population Genetics and a Wellcome Senior Research Fellow in Clinical Medicine at the University of Oxford. His research is into the morphogenic signalling pathways that control the intestinal stem cell in homeostasis, regeneration and cancer, and he has published more than 80 peer reviewed papers in journals that include Nature Medicine, Nature Genetics, Gastroenterology and Gut. Simon’s research has been recognised by the United European Gastroenterology Rising Star award in 2010, the British Society of Gastroenterology Francis Avery Jones research prize in 2015 and the CRUK future leaders prize in 2017. In ACRCelerate, Oxford have led on mouse tumour phenotypic, including assessing the stem cell molecular phenotype and developing multiplex immune panels for assessing primary tumour and metastatic lesion cell interactions. We have also a co-led (with Glasgow) on the application of radiation therapy in mouse models.

People involved:

Barcelona, Spain

Prof Josep Tabernero

Head, Medical Oncology Department
Vall d’Hebron University Hospital (HUVH)
Director, Vall d’Hebron Institute of Oncology (VHIO)
Vall d’Hebron Hospital Campus
Barcelona
Josep Tabernero email: jtabernero@vhio.net

Hector Garcia Palmer email: hgpalmer@vhio.net

Elena Élez email: meelez@vhio.net

Website link: VHIO GI and endocrine tumours

Website link: VHIO Stem cells and cancer

Josep Tabernero and Elena Élez, are co-investigators and top-recruiters of the BEACON Trial. The practice-changing phase III BEACON trial evaluated targeted therapy for dual and triple targeted blockade in refractory BRAFV600E mCRC. Patients were randomly assigned (1:1:1) to receive the encorafenib plus cetuximab, encorafenib plus cetuximab plus binimetinib; or an irinotecan-based chemotherapy plus cetuximab as standard of care (SOC). The doublet combination was approved for adults with BRAFV600E mCRC and who have already undergone at least one prior treatment regimen (May 2020).

Hector Palmer’s Lab, in collaboration with clinical investigators are generating numerous PDX from CRC patients with different clinical profiles. A new GEMM has been generated to study hypermutant MSI CRC with Braf^V600E mutation. A biobank of Msh2KO, Braf^V600E and Msh2KO- Braf^V600E organoids and syngeneic models is being created. Multiple rational drug combinations are showing activity controlling the growth of CRC PDXs and now we are testing our organoid and syngeneic mouse models. Finally, a comprehensive project to evaluate resistance to BRAFV600E inhibitors in collaboration with Novartis is currently running using PDX models collection. This is of high relevance since advanced CRC patients treated with anti-BRAFV600E-based therapies are currently progressing to treatments in several active clinical trials (e.g. BEACON trial).

People involved:

Prof Eduard Batlle

Group Leader 
IRB - Institute for Research in Biomedicine
Barcelona, Spain
Eduard Batlle email: eduard.batlle@irbbarcelona.org 

Website link: https://www.irbbarcelona.org/en/research/colorectal-cancer-laboratory

My lab conducts frontier research to understand the role of the tumor microenvironment during colorectal cancer (CRC) progression, as well as the relation between stem cells (SCs) and cancer in the intestine.  We perform fundamental research using innovative model systems and technologies on topics that are often clinically relevant.  Over the past few years, my lab has devoted large efforts to understand the determinants of metastatic dissemination in CRC. We discovered that metastasis in CRC is a cancer cell non-autonomous process that depends on a TGF-beta-driven gene program expressed in stromal cells (Calon et al. Cancer Cell 2012, Calon et al. Nature Genetics 2015).

Moreover, we established a pre-clinical model of metastatic CRC in an immunocompetent background and demonstrated that checkpoint immunotherapies are effective against metastatic CRC in the presence of TGF-beta inhibitors (Tauriello et al. Nature 2018).

This research line holds a great potential to change the clinical management of CRC patients.  We are leveraging our knowledge and expertise in order to:

1. Develop methods to stratifycancer patients based on measuring the expression of stromal genes in patient samples
2. Characterise the changes in the tumour microenvironment of metastatictriggered by inhibition of the TGF-beta pathway and treatment with checkpoint immunotherapies
3. Develop novelbased on organoids to reproduce disease relapse. This model will allow pre-clinical evaluation of adjuvant therapies in a human-like model that mimics disease relapse in CRC after curative therapy.

People involved:

Elena Sancho	Project Manager
Xavier Hernando-Momblona	Lab Technician
Ana Henriques	PostDoc
Adrià Cañellas	Student
María Salvany	Student

   

Prof Manel Esteller

Director
IJC - Josep Carreras Leukaemia Research Institute 
Barcelona, Spain
Manel Esteller email: mesteller@carrerasresearch.org 

Website link: https://www.carrerasresearch.org/en/cancer-epigenetics_124284 

Manel Esteller graduated in Medicine from the Universitat de Barcelona (Spain), where he also obtained his PhD in Molecular Genetics. Dr. Esteller was a Postdoctoral Fellow and a Research Associate at the Johns Hopkins University (US) where he studied DNA methylation and human cancer. His work was decisive in establishing promoter hypermethylation of tumor suppressor genes as a common hallmark of cancer.

From October 2001 to September 2008 Manel Esteller was the leader of the Cancer Epigenetics Laboratory at the Spanish National Cancer Center (CNIO), where his principal area of research were the alterations in DNA methylation, histone modifications and chromatin in human cancer. Since October 2008 until May 2019, Dr Esteller was the Director of the Cancer Epigenetics and Biology Program (PEBC) in Barcelona. He is currently the Director of the Josep Carreras Leukaemia Research Institute (IJC) in Barcelona, Chairman of Genetics in the School of Medicine of the University of Barcelona, and an ICREA Research Professor.

His current research is devoted to the establishment of the epigenome maps in health and disease. As a well-recognized expert in the epigenetics field, Dr. Esteller is leading the epigenomic characterization of patient-derived xenograft (PDX) models developed by the ACRCelerate consortium using the latest platform from Illumina, the Human Methylation EPIC Beadchips that allows to interrogate the methylation status of almost a million of genome-wide distributed CpGs. Moreover, Dr. Esteller’s team in currently validating the first comprehensive mouse DNA methylation microarray that will be a key tool to characterize the epigenomic landscape of colorectal cancer mouse models developed under the umbrella of this project. The epigenomic data derived from both approaches, PDXs and murine models, will provide crucial information to improve the molecular stratification of colorectal cancer patients. Moreover, the knowledge generated with this strategy could be useful to identify novel targets for therapeutic intervention.

People involved:

Veronica Davalos	Associate Researcher
Pedro Blecua	Associate Researcher
Margalida Rosello	PhD student
Laila Aledon	Technician
Carles Arribas	Technician
Veronica Padial	Project Manager

 

Dr Ramon Salazar 

General Director Catalan Institute of Oncology (ICO)
Bellvitge Biomedical Research Institute (IDIBELL)
Barcelona
Ramon Salazar Soler email: RamonSalazarSole@iconcologia.net 

Website link: Dr Ramon Salazar IDIBELL

Dr Salazar has served as Head of Medical Oncology Department at the Catalan Institute of Oncology in L'Hospitalet de Llobregat, since 2015 until April 2022 and is a cross-referent of Digestive Pathology in Medical Oncology at ICO. He had previously been in charge of the Phase 1 Unit; Head of Corporate Translational Research and Director of Research at ICO.

Dr Salazar has been the coordinator of the Molecular Mechanisms and Experimenal Therapy in Oncology program in IDIBELL until December 2020. He also served as a member of the Executive Committee of Gastrointestinal Tract Tumors Group at the European Organisation for Research and Treatment of Cancer (EORTC), of the Spanish group for the treatment of tumors of the digestive tract (TTD), the faculty committee of the European Society of Medical Oncology ( ESMO) for digestive tumors and has served at the Advisory Board of the European Society of Neuroendocrine Tumors (ENETS). He also was the founding president of the Spanish Group of Neuroendocrine Tumors (GETNE).

Dr. Salazar has published more than 200 articles in peer reviewed medical journals, 60 of them in the last five years, and has written numerous book chapters and monographs on colorectal cancer and gastrointestinal neuroendocrine tumors.

One of the most important contributions of Dr Salazar’s team has been made in the description of the new colorectal cancer classification, the Consensus Molecular Subtypes, which describes 4 molecular subtypes with an important impact on the future clinical and translational research in this disease. Following this line of research, he participated as an academic researcher in an international project led by Dr. Tabernero and funded by the European Union program Horizon 2020. The project MoTriColor in a very innovative way, intended to develop clinical trials with drugs selected for a population of patients with metastatic CRC molecularly characterized by gene expression signatures based on the new classification of molecular consensus CMS 1‐4 (Mo TriColor.eu).

The research lines led by Dr. Ramon Salazar are mainly focused on discovery and validation of new molecular diagnostic, prognostic and predictive signatures and identification or optimization of new therapeutic targets and molecular classifications.

People involved:

Cristina Santos Vivas	(MD, PhD), principal investigator
Alberto Villanueva	(PhD) investigator
Antonio Gentilella	(PhD) investigator
Paula Fernández Calotti	Scientific project manager

Turin, Italy

Prof Livio Trusolino

Professor
The Candiolo Cancer Institute (IRCC)
University of Torino Medical School
Livio Trusolino email: livio.trusolino@ircc.it

Website link: https://www.irccs.org/translational-cancer-medicine

Research conducted in Livio Trusolino’s laboratory aims at exploring the mechanisms underlying tumour dependencies on defined oncogenic drivers or pathways and how such dependencies can be translated into therapeutic opportunities, with an emphasis on colorectal cancer. This goes along with the implementation of studies that correlate clonal competition with fitness effects as a means to understand whether variations in fitness landscape are dictated by clonal selection of heritable genomic traits or by non-genetic mechanisms impacting on cell phenotypes. To these objectives, Livio uses integrative multi-omic approaches and functional genomics in patient-derived xenografts and organoids.

People involved:

PDX FINDER - open global cancer research portal to patient derived xenograft models

Patients-derived xenograft (PDX) mouse models are an important oncology research platform to study tumour evolution, drug response and personalised medicine approaches. However, because of the distributed and heterogeneous nature of PDX repositories, finding relevant models of interest to investigators is a challenge. The global success of PDX models will depend on their collective distribution and usage worldwide by academic and private sectors.

To facilitate PDX models discovery, EMBL-EBI and The Jackson Laboratory are co-developing PDX Finder – a comprehensive open global catalogue of PDX models and their associated data across resources. In support of this initiative, we coordinated the community initiative to develop the PDX Models Minimal Information Standard (PDX-MI) that defines the minimal information necessary for describing key elements of a PDX model including the clinical attributes of a patient’s tumour, methods of implantation, host strain, and quality assurance methods used for model validation.

PDX Finder

Milan, Italy

Prof Alberto Bardelli

Scientific Director of IFOM
IFOM ETS - the AIRC Institute of Molecular Oncology
Milan
Alberto Bardelli email: alberto.bardelli@unito.it

Website link: https://www.ifom.eu/en/cancer-research/researchers/alberto-bardelli.php

The ultimate goal of the ACRCelerate Project is to improve the next generation of stratified trials for CRC, through accurate disease subtype positioning. This will be achieved with rapid and robust cross-validation of concepts across a suite of “state of-the art” models, at a rate and scale that would be unachievable by an individual center. These include new model systems with patient-derived xenografts (PDX), patient and PDX derived cell-lines (PDCL and PDXCL) and organoid models.

One aspect of the project is to perform preclinical testing of agents and combination therapies within defined target groups.

Bardelli’s group has developed a large collection of CRC cell lines, drug-resistant cells and tumour (patient or PDX-derived) derived cells. CRC cell lines have specific molecular features and will support the stratification of therapies that target cell intrinsic tumour mechanisms. They have performed a systematic screening with chemotherapeutic agents (5-fluorouracil, oxaliplatin, irinotecan metabolite) in a group of over 100 cell lines recapitulating the genomic landscape of colorectal cancer and plan to investigate on potential correlations between the genomic milieu and the pharmaco-response profiles obtained in different CRC models.

To begin mechanistically dissecting effective combinatorial therapies in CRC, in 2020 they reported how in CRC, KRAS G12C inhibitors needed to be combined with EGFR blocking agents in order to overcome drug resistance to these targeted agents. Most excitingly, the first patients treated with the proposed combination showed tumor regression on scans in January 2021, less than a year after our publication. Overall our preclinical experiments therefore continue to provide the rationale for innovative clinical trials.

People involved:

Dr Elisa Mariella	Post-doc
Dr Martina Miotto	Researcher
Prof Sabrina Arena	Collaborator
Dr Luca Lazzari	Collaborator

Website link: https://www.irccs.org/molecular-oncology