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Cancer Research UK Manchester Institute SCIENTIFIC REPORT 2019

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Cancer Research UK Manchester Institute SCIENTIFIC REPORT 2019 SCIENTIFIC REPORT 2019 cruk.org SCIENTIFIC COVER IMAGE Primary cutaneous melanoma (nests of purple cells) invading the dermis. The specimen is REPORT stained with Masson’s trichrome stain. Cyan blue reveals collagen fibre architecture. Image supplied by Amaya Viros (Skin Cancer 2019 and Ageing) MANCHESTER INSTITUTE CONTENTS DIRECTOR’S INTRODUCTION 04 Tim Somervaille 32 RESEARCH SERVICES RESEARCH PUBLICATIONS 64 RESEARCH HIGHLIGHTS 2019 07 Leukaemia Biology Duncan Smith 52 THESES 69 Richard Marais 34 Biological Mass Spectrometry Facility SEMINAR SERIES 2019 70 CANCER RESEARCH UK Molecular Oncology Jen Hughes and Lisa Doar 53 MANCHESTER INSTITUTE OPERATIONS 72 Esther Baena 36 Biological Resources Unit Prostate Oncobiology Wolfgang Breitwieser 55 POSTGRADUATE EDUCATION 80 RESEARCH GROUPS Molecular Biology Core and CANCER RESEARCH UK’S LOCAL 84 Caroline Dive 14 Amaya Virós 38 Computational Biology Support Facility ENGAGEMENT AND DEVELOPMENT Cancer Biomarker Centre Skin Cancer and Ageing Georges Lacaud 40 Garry Ashton 56 ACKNOWLEDGEMENT FOR FUNDING OF 86 Santiago Zelenay 20 THE CANCER RESEARCH UK Stem Cell Biology Histology Cancer Inflammation and Immunity MANCHESTER INSTITUTE Claus Jørgensen 42 Natalia Moncaut 56 Iain Hagan 22 CAREER OPPORTUNITIES AT THE CANCER 87 Systems Oncology Transgenic Production Facility Cell Division RESEARCH UK MANCHESTER INSTITUTE Marek Dynowski 58 Maximiliano Portal 24 Michela Garofalo 44 Scientific Computing CONTACT DETAILS 88 Cell Plasticity & Epigenetics Transcriptional Networks in Lung Cancer Jeff Barry 59 Angeliki Malliri 26 Robert Bristow 46 Flow Cytometry Cell Signalling Translational Oncogenomics Steve Bagley 60 Caroline Springer 28 Patricia Muller 48 Visualisation, Irradiation & Analysis Drug Discovery Tumour Suppressors Robert Metcalf 30 Head and Neck Cancer Biology The Cancer Research UK Manchester Institute is temporarily located at Alderley Park in Cheshire until we return to our original site in The Oglesby Cancer Research Building. Withington. Some research groups and staff remain in the Oglesby Cancer Research Building. 2 SCIENTIFIC REPORT 2019 CANCER RESEARCH UK MANCHESTER INSTITUTE 3 Sciences at The University of Manchester, prostate cancer progression and treatment together with colleagues in the Leukaemia response. Biology group, uncovered an intriguing DIRECTOR’S relationship between splicing and epigenetic Our early career researchers’ efforts were regulation underpinning a new molecular recognised at several meetings during the INTRODUCTION subtype of Acute Myeloid Leukaemia. summer. Postdoctoral Research Fellow, Lucas Alongside, the Leukaemia Biology group Trucco, from the Molecular Oncology team continue to develop their programme on the received the AACR Scholar-in-Training Award to potential AML target Lsd1 and have identified attend the AACR Annual Meeting, while Brian mTORC1 inhibition as a synergistic therapeutic Lee from Systems Oncology was awarded a approach. poster prize at the BACR Tumour Microenvironment meeting. Several of our PhD During 2019 we continued our recovery from the 2017 Paterson I was delighted that the DETECTION clinical trial students attended the International PhD Student was funded by CRUK and that the CACTUS trial Cancer Conference in Amsterdam, with two of Building fire by consolidating our interim base at Alderley Park. is now up and running. Both applications for our students, Max Schenk and Chris Bromley, The Paterson Building has been demolished and good progress these melanoma trials have been driven by winning prizes for their presentations. Sakis Rebecca Lee, a former clinical fellow in the Paliouras received a University of Manchester is being made on the plans for its replacement. Molecular Oncology group, and rely on the Doctoral Academy Graduate Society ctDNA expertise developed in the CBC. Also, conference award and a BACR-CRUK student many of our Group Leaders contributed to the travel award to attend the AACR annual meeting. The project received a significant boost in the patients following lung cancer surgery with the Professor successful application for an Academic In July, the MCRC and Experimental Cancer summer through a £25m award from the aim of using these “liquid biopsy” approaches to Researcher Clinical Training Innovation in Medicine Centre organised an exciting meeting Richard Marais Research England UK Research Partnership detect relapse at an early stage. The TARGET Cancer programme (ARCTIC) as part of the in Manchester “Phase 1: Where Science Investment Fund and towards the end of 2019, trial has been another exciting development for CRUK Manchester Centre’s Clinical Academic Becomes Medicine” at which Julie Stevenson Director of the Cancer Research the Rewrite Cancer campaign was launched by the CBC in recent years, together with clinical UK Manchester Institute Training (CAT) initiative and we look forward to and Paul O’Regan from the digital Experimental the project's partners to raise the final £20m colleagues at the Christie Hospital. This ctDNA- welcoming some of the trainees to CRUK MI in Cancer Medicine Team were jointly awarded required for the build. As 2020 proceeds, we driven selection phase I clinical trial is being run due course. Our scientists also played a major prizes for their posters on eTARGET - a digital look forward to finalising the design and across Experimental Cancer Medicine Centres role in the success of several other CRUK solution for the Manchester Molecular Tumour watching the new facility start to emerge and in the North and was also published in a Nature Manchester Centre initiatives such as the ACED Board. PhD students Denys Holovanchuk, Amy take shape. Medicine publication, and the trial will now be early detection alliance and the radiation McCarthy and Jakub Chudziak all received expanded to assess patient survival. It is very research network RADNET, while the Belfast- awards to attend conferences, Amin Ali received Despite the disruption of the move, we have pleasing to see how well the CBC has recovered Manchester Movember Centre of Excellence for The University of Manchester’s Presidential celebrated many scientific highlights that from the fire. Prostate Cancer, which involves three of our Award and Joe Maltas was awarded The illustrate the depth and breadth of research at research groups, was renewed in 2019. Humane Research Trust Margaret Pritchard the Institute. It was a particularly successful year The Institute’s Drug Discovery Unit (DDU) has Moreover, together with partners in Italy and Memorial Prize. Postdoctoral Research Fellow for the Institute’s Deputy Director Caroline Dive also made an excellent recovery, since Spain, the CBC’s digital Experimental Cancer Victoria Pelly received a CRUK Research Travel and her Clinical and Experimental establishing their facilities at Alderley Park in Medicine Team were awarded a CRUK Award, which facilitated a visit to the group of Pharmacology group who continue to be at the early 2018. Their programme of greater Accelerator award to produce digital tools for Ton Schumacher at the NKI. We have continued forefront of the development of biomarkers to integration with the Institute’s scientists is clinical teams across the CRUK Experimental to celebrate our achievements in pursuing aid clinical decision making. In April, they developing well in addition to fostering exciting Cancer Medicine Centres’ network providing developments in the principles of the 3Rs – received an “Outstanding” rating at their new collaborations with the wider CRUK real-time access to patient data to facilitate Replacement, Reduction and Refinement – quinquenniual review, which took place over community including a joint position with faster clinical decision-making. Georges during in vivo procedures and to promote two days at Alderley Park. Later in the year, they Stephen Taylor at The University of Manchester, Lacaud, who leads the Stem Cell Biology group, sharing and dissemination of ideas and best were part of the successful renewal of the CRUK and a second joint position with Richard Bayliss received funding from the charity Bloodwise practice, we held a joint 3Rs’ Poster event with Lung Cancer Centre of Excellence, and towards at The University of Leeds. They published two (now Blood Cancer UK) to investigate MOZ AstraZeneca and Agenda Life Sciences. I am the end of the year, we renamed the group as studies in 2019 that are the first to describe orally histone acetyl transferase activity in leukaemia. delighted that CRUK MI picked up awards in all the Cancer Research UK Manchester Institute available drug-like compounds against lysyl three categories at this event, through the work Cancer Biomarker Centre (CBC) to recognise oxidase (LOX). This enzyme forms cross-links A number of our staff and students received of Lisa Doar, Chris Below, Callum Hall and the scope and extent of their exciting scientific between collagens and elastin in the awards and prizes during the year. Caroline Dive Yannick von Grabowiecki. activities. We also welcomed Dr Alistair Kerr and extracellular matrix and plays a critical role in was one of The University of Manchester’s Dr Carlos Garcia Lopez to the CBC as the new regulating tumour growth and metastasis. Their Researcher of the Year, and she received the Junior Group Leader Santiago Zelenay received Head of the Bioinformatics and Biostatistics work has added to the growing interest in LOX 2019 Heine H. Hansen Lectureship Award for the inaugural BIAL Prize in Biomedicine, along team, and as an Institute Fellow respectively.
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