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Paterson Institute for Cancer Research SCIENTIFIC REPORT 2012

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Paterson Institute for Cancer Research SCIENTIFIC REPORT 2012 SCIENTIFIC REPORT 2012 cruk.org Cover image Dr Andrew Porter, a Post-doctoral Research Fellow in the Cell Signalling Group. SCIENTIFIC REPORT 2012 CONTENTS SECTION 1 SECTION 2 DIRECTOR’S INTRODUCTION 04 THE UNIVERSITY OF MANCHESTER, RESEARCH HIGHLIGHTS 07 INSTITUTE OF CANCER SCIENCES THE PATERSON INSTITUTE FOR RESEARCH GROUPS CANCER RESEARCH Vaskar Saha 50 Children’s Cancer RESEARCH GROUPS Robert Hawkins 52 Crispin Miller 14 Medical Oncology: Clinical and Applied Computational Biology Experimental Immunotherapy and Bioinformatics Gordon Jayson 54 Geoff Margison 16 Medical Oncology: Translational Carcinogenesis Anti-Angiogenesis Karim Labib 18 Tim Illidge 56 Cell Cycle Targeted Therapy Iain Hagan 20 Catharine M. L. West 58 Cell Division Translational Radiobiology Nic Jones 22 Cell Regulation SECTION 3 Angeliki Malliri 24 RESEARCH SERVICES Cell Signalling Steve Bagley 62 Caroline Dive 26 Advanced Imaging and Flow Cytometry Clinical and Experimental Duncan Smith 63 Pharmacology Biological Mass Spectrometry Ivan Ahel 30 Biological Resources Unit 64 DNA Damage Response Garry Ashton 65 Donald Ogilvie 32 Histology Drug Discovery Mark Craven 66 Peter L. Stern 34 Laboratory Services Immunology Stuart Pepper 67 Nullin Divecha 36 Molecular Biology Core Facility Inositide Laboratory The Paterson Institute Tim Somervaille 38 RESEARCH PUBLICATIONS 68 Leukaemia Biology THESES 79 Richard Marais 40 Molecular Oncology EXTERNAL SEMINAR SPEAKERS 2012 80 John Brognard 42 POSTGRADUATE EDUCATION 82 Signalling Networks in Cancer OPERATIONS 84 Georges Lacaud 44 CANCER RESEARCH UK’S Stem Cell Biology RESEARCH ENGAGEMENT 88 Valerie Kouskoff 46 ACKNOWLEDGEMENT FOR FUNDING OF Stem Cell and Haematopoiesis THE PATERSON INSTITUTE 90 CAREER OPPORTUNITIES AT THE PATERSON INSTITUTE 91 CONTACT DETAILS 92 2 SCIENTIFIC REPORT 2012 THE PATERSON INSTITUTE FOR CANCER RESEARCH 3 Development of a the winner of the University of Manchester DIRECTOR’S INTRODUCTION pharmacodynamic Institute of Cancer Sciences/PICR postgraduate circulating tumour cell assay: student of the year award. Bill used chemical Spiked tumour cells (green) and white blood cells (blue) inhibitors that had been synthesised by the Drug recovered from a whole blood Discovery Group to down-regulate KDM1A and sample by ‘Isolation by Size of the success of the approach has resulted in this Epithelial Tumour Cells’ (ISET). A potential therapeutic strategy progressing drug target (red) can be towards clinical trials. quantified, providing a potential pharmacodynamic biomarker for novel targeted therapies. The tough financial climate, in which we find CD45: Blue, Cytokeratin: Green, ourselves, presented us with significant Drug Target: Red. Image challenges in 2012 and will continue to do so provided by Robert Sloane from over the next couple of years. A major focus It is a privilege to have taken on the Directorship of the the Clinical and Experimental Pharmacology Group. going forward is to use our core grant from Paterson Institute and my first year in post has been highly Cancer Research UK to leverage additional enjoyable. This report offers a chance to look back at the John Brognard in 2010 and the intense activity funding from external sources in order to carry in this area within the Clinical and Experimental out the full breadth of research that we wish to developments that have taken place and an opportunity to Pharmacology Group. undertake. Gill Campbell joined us during the discuss our ambitions for the future. A major highlight of the year as a Grants Advisor to help facilitate this. An ongoing goal is to promote translational Successful external funding applications year was the successful bid, made with colleagues at the research at the Paterson Institute. A major increased dramatically in 2012 and successful Professor Richard Marais activity in this respect is provided by the Clinical grants included a Wellcome Trust Senior Director of The Paterson University of Manchester and the Manchester Cancer Institute for Cancer Research and Experimental Pharmacology Group led by Investigator Award (Richard Marais) and Research Centre, to the UK Research Partnership Caroline Dive. This year the CEP Biomarker significant funding from Leukaemia and Investment Fund which resulted in an award of £12.8m Portfolio has expanded to include a Nucleic Lymphoma Research (Georges Lacaud, Tim Acids Biomarkers (NAB) team, led by CEP Somervaille, Peter Stern) and the Pancreatic towards our aim of implementing personalised medicine Deputy Ged Brady, which is dedicated to Cancer Research Fund (Caroline Dive and Ged for cancer patients in the North West. developing the current validated CEP blood- Brady). based NAB assays. To do so, NAB projects have been initiated to examine miRNA and In addition to the major boost provided by the The funds provide £4.1m towards completion of development in his new post at the Juntendo methylation patterns present in circulating free UKRPIF award, there have been further exciting the new Manchester Cancer Research Centre University School of Medicine in Tokyo. DNA, RNA profiling and mutation detection in developments in the core research facilities. A (MCRC) research building which is currently Successful quinquennial reviews were circulating tumour cells. CEP successfully successful bid was made to the MCRC for funds under construction across the road from the undertaken by Crispin Miller (Applied re-negotiated their contract with AstraZeneca, to purchase a multi-modal imaging system Paterson Institute and due for completion in Computational Bioinformatics and Biology) and worth £3.1million over three years, to continue which will include far-field super-resolution 2014, while the remaining £8.7m will go towards Iain Hagan (Cell Division). My own research their alliance covering blood borne serological imaging via gated Stimulation Emission specialised equipment , the majority of which team focuses on signalling through the RAS/RAF biomarker assays. Caroline was awarded the Depletion (STED) and two-photon confocal will be housed in the Paterson Institute core pathway and the role that this plays in the highly prestigious Pasteur-Weizmann/Servier microscopy. We shall be the first site in the UK to facilities and will support research across both development and progression of melanoma. Prize and Tribute. This well-deserved honour is have such a capability which will put us at the buildings. This will help us to progress the basic The group is now established in the Institute in recognition of the fantastic work by Caroline forefront of super-resolution imaging on live and translational research that is pivotal to the with eight new members in addition to five and her group in developing minimally-invasive cells and have a major impact on a range of development of further novel anti-cancer Postdoctoral Fellows who have joined me in biomarker tests for a range of cancers and projects across the Institute. We said farewell to treatments and to accelerate the development moving here from the Institute of Cancer treatments. Morgan Blaylock after five very successful years of approaches that will lead to improved Research in London. building up our Flow Cytometry Facility. Steve outcomes for patients. We have made a start on The Drug Discovery Group continue to make Bagley now oversees this service after its merger acquiring the necessary technologies with the A key objective at the Institute for the coming good progress and have two active phase with Advanced Imaging. Several new members installation of two next generation sequencing year is to recruit four new Junior Group Leaders. projects in collaboration with core Group of staff have been recruited who will work platforms which will greatly expand our These new appointments will help strengthen Leaders (Tim Somervaille and Ivan Ahel) and across Imaging, Flow Cytometry and Histology capabilities in this area. The remaining the Institute’s portfolio in translational research three pre-projects with core Group Leaders to provide an integrated service for users. purchases will be made over a three year period and will focus on our areas of priority, which (John Brognard, Ivan Ahel and Karim Labib). The Significant refurbishment work and updating of which will allow us to take advantage of rapidly include lung cancer, pancreatic cancer, increasing synergy between DDG and CEP was equipment has resulted in improvements to evolving technology across many of the women’s cancers and molecular pathology. enhanced this year by the joint appointment of Laboratory Services while the Biological relevant platforms. These themes are largely aligned with the an in vivo scientist who will be responsible for Research Unit has had a busy year relocating cancer research strategy of our local MCRC progressing the DDG portfolio. The advantages transgenic services to our new facility at the During the summer, Geoff Margison, leader of partners, the University of Manchester and The of embedding Drug Discovery within the University which will allow for much needed the Carcinogenesis group, retired from the Christie NHS Trust, a joint strategy that has been Institute have been clearly illustrated by another expansion of our experimental capability. Institute after an association extending back developed over the past year and has major highlight of the year which was the over forty years. He continues his research with personalised medicine at its core. Critically, the publication by Tim Somervaille’s Leukaemia It is also a pleasure to note some further an
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