Introduction

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Select Research Group Head Prof. Sir Tom Blundell Prof. Kevin Brindle Dr Bill Broadhurst Dr Guy Brown Dr Mark Carrington Prof. Paul Dupree Prof. Gerard Evan - Head of Dept Prof. Richard Farndale Dr Giorgio Favrin Dr Jenny Gallop Dr Nick Gay Dr Andrew Grace Dr Jules Griffin Dr Brian Hendrich Dr Andrew Hesketh Dr Robin Hesketh Dr Matt Higgins Dr Florian Hollfelder Dr Hee-Jeon Hong Prof. Chris Howe Dr Marko Hyvonen Prof. Steve Jackson Dr Tony Jackson Prof. Richard Jackson Prof. Ernest Laue Prof. Peter Leadlay Dr Kathryn Lilley Dr Karen Lipkow Dr Rick Livesey Prof. Ben Luisi Dr Sarah Lummis Dr Juan Mata Dr John McCafferty Prof. Jim Metcalfe Dr Masanori Mishima Dr Eric Miska Dr Tom Monie Dr Helen Mott Dr Natasha Murzina Dr Daniel Nietlispach Dr Darerca Owen Prof. Steve Oliver Dr Luca Pellegrini Dr Markus Ralser Dr Nick Robinson Prof. George Salmond Dr Deirdre Scadden Dr José Silva Prof. Austin Smith Prof. Chris Smith Dr Nancy Standart Prof. Dame Jean Thomas Dr Aviva Tolkovsky Dr Martin Welch Dr Joyce Wong Dr Nianshu Zhang

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Select by Subject or Manager DNA Sequencing Facility . . . . . Mr John Lester _______________________________ Quantitative Proteomics . . . . . Dr Kathryn Lilley _______________________________ Proteomics Core Services . . . . . Dr Mike Deery _______________________________ Protein & Nucleic Acid Chemistry . . . . . Dr Len Packman _______________________________ Metabolomics . . . . . Dr Jules Griffin _______________________________ Baculovirus Facility . . . . . Dr Darerca Owen _______________________________ Biophysics Facility . . . . . Dr Katherine Stott _______________________________ Crystallographic X-ray Facility . . . . . Dr Dima Chirgadze _______________________________ NMR spectroscopy . . . . . Dr Daniel Nietlispach _______________________________ Fermentation Facility . . . . . Dr Nianshu Zhang _______________________________ Bioinformatics & Computational Biology Services . . . . . Dr Jenny Barna _______________________________ Computer & IT Support . . . . . Dr Erik Timmers _______________________________

Past members last known active weblink

Select past member of Department Dr Stephen Bell Prof. Jonathan Blackburn Dr David Brown Dr Pak-Lee Chau Dr Hal Dixon (deceased) Dr Jessica Downs Prof. David Ellar Dr Paul Kemp Dr Simon Lovell Dr Kenji Mizuguchi Dr Massimo Paoli Prof. Richard Perham Dr Peter Reynolds Dr Philip Rubery Dr Gerry Smith Dr Margaret Sunde Prof. Jamie Vandenberg Dr Kira Weissman

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Using Switchable Mouse Genetic Models to Validate Therapeutic Cancer Targets

Research Groupings: Cancer

Cancers are lethal disease in desperate need of new therapeutic approaches: despite dramatic advances in the use of conventional chemo and radiotherapy and the growth of more “targeted” drugs, many cancers are still incurable. The principal problem is that we have no systematic or informed way of predicting which, out of the legion of aberrant processes in pancreatic cancer cells, is the best to target with drugs or where, within that process the most effective molecular targets lie. To address this problem, we employ a novel class of genetically engineered mouse (GEM) in which individual oncogenes and/or tumour suppressor genes may be systemically toggled off and on, reversibly and at will, in vivo. In this way we can identify the most effective therapeutic targets irrespective of contemporary (and ephemeral) prejudices as to their “druggability”.

This approach is well illustrated by two such GEMs: one mouse that models pharmacological inhibition of Myc, a core component of the replicative machinery of all tumour and normal cells and a downstream conduit for many (perhaps all) oncogenic growth signals, and second mouse that models pharmacological restoration of the p53 tumour suppressor that is functionally inactivated in most human cancers. Since it is the endogenous oncogene or tumour suppressor that is toggled in such GEMs, they can be easily applied to any existing or new preclinical mouse cancer model. Using these two GEMs, we have directly ascertained the therapeutic impact, efficacy and side effects of Myc inhibition and p53 restoration - establishing both mechanism of action and therapeutic index.

Lab members
Deborah Burkhart, Adam Guterres, Ivonne Gamper, Stephanie Hall, Peter Kreuzaler, Trevor Littlewood, Dan Lu, Fiona McDuff, Luca Pellegrinet, Alessandra Perfetto, Ana Rebocho, Nick Salisbury, Nicole Sodir, Catherine Wilson

References