Dr Paul Timpson

Lab Head - Invasion and Metastasis

Conjoint/Adjunct Role(s)

Conjoint Senior Lecturer, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney

Paul completed his PhD with Prof Margaret Frame at the Beatson Institute for Cancer Research, UK in 2002 where he assessed the interplay between Src family kinases and the actin cytoskeleton during cancer cell invasion, focusing on the role of Rho family GTPases. He then moved to the Garvan Institute in 2003 to work with Professor Roger Daly investigating the role of the actin-binding protein cortactin in growth factor receptor trafficking in breast cancer and head and neck cancers.

Paul was awarded an AstraZeneca Postdoctoral Research Fellowship allowing him to return to the Beatson Institute in 2007, to work with Professor Kurt Anderson in collaboration with AstraZeneca Advanced Technology Laboratories. This ongoing work has focused upon the development of novel multi-disciplinary live imaging techniques to investigate molecular dynamics of cancer cells in vivo.

Returning to Australia to establish a research group in November 2012 within the Cancer Program, Paul aims to understand disease in the context of the surrounding environment using cutting edge in vitro and in vivo imaging technology. Pinpointing the molecular drivers of cancer progression and the environmental cues that cause resistance to current systemic therapy are the focus of his research.

Research Interests

Intravital imaging
Invasion & metastasis
tumour associated microenvironment
Pre-clinical imaging
Biosensors & drug discovery
RhoGTPases
E-cadherin cell-cell junctions
Src family kinases
Signal transduction
3D-modelling of disease

Awards and Honours

2012-2016 - Australian Research Council (ARC) Future Fellowship, Australia
2013-2016 - CINSW Fellowship, NSW, Sydney, Australia
2010-2012 - Cancer Research UK, CRUK posdoctoralResearch Award, UK
2011 - European Association for Cancer Research Award (EACR) Australia
2010 - Actin Prize 2010, Bristol, UK
2007-2010 - AstraZeneca Research Fellowship, UK
2004 - AMGEN Postdoctoral Early Career Research prize, Australia
2001 - Cancer Research Campaign, PhD Award, London, UK
2001 - Beatson Institute PhD Career Development award, Glasgow, UK
1998 - GlaxoWellcome, University (Hons) award, Pharmacology, UK

Education

2002 - PhD, The University of Glasgow - UK
1998 - BSc joint (Hons) Class I, Immunology & Pharmacology, The University of Strathclyde - UK

Selected Publications

Claire Vennin, Venessa T. Chin, Sean C. Warren, Morghan C. Lucas, David Herrmann, Astrid Magenau, Pauline Melenec, Stacey N. Walters, Gonzalo del Monte-Nieto, James R.W. Conway, Max Nobis, Amr H. Allam, Rachael A. McCloy, Nicola Currey, Mark Pinese, Alice Boulghourjian, Anaiis Zaratzian, Arne S.A. Adam, Celine Heu, Adnan M. Nagrial, Angela Chou, Angela Steinmann, Alison Drury, Danielle Froio, Marc Giry-Laterriere, Nathanial L.E. Harris, Tri Phan, Rohit Jain, Wolfgang Weninger,  Ewan J. McGhee, Renee Whan, Amber L. Johns, Jaswinder S. Samra, Lorraine Chantrill, Anthony J. Gill, Maija Kohonen-Corish, Richard P. Harvey,  Andrew V. Biankin, Australian Pancreatic Cancer Genome Initiative (APGI), T.R. Jeffry Evans, Kurt I. Anderson, Shane T. Grey, Christopher J. Ormandy, David Gallego-Ortega, Yingxiao Wang, Michael S. Samuel, Owen J. Sansom, Andrew Burgess, Thomas R. Cox, Jennifer P. Morton, Marina Pajic# and Paul Timpson(2017) Transient tissue ‘priming’ via ROCK manipulation uncouples pancreatic cancer progression, chemo-resistance and the onset of the metastatic niche. Science Translational Medicine, 9(384). doi: 10.1126/scitranslmed.aai8504. # corresponding authors fulltext

James R.W. Conway, Sean C. Warren and Paul Timpson# (2017) Context-dependent intravital imaging of therapeutic response using intramolecular FRET biosensors. Methods doi: 10.1016/j.ymeth.2017.04.014. # corresponding author

Nathanial L.E. Harris, Claire Vennin, James R.W. Conway, Kara L. Vine, Mark Pinese, Mark J. Cowley, Robert F. Shearer, Morghan C. Lucas, David Herrmann, Amr H. Allam, Marina Pajic, Jennifer P. Morton, Australian Pancreatic Cancer Genome Initiative, Andrew V. Biankin, Marie Ranson#, Paul Timpson# and Darren N. Saunders# (2017) SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer. Oncogene, Mar 27. doi: 10.1038/onc.2017.63. # corresponding authors

Claire Vennin, David Herrmann, Morghan C. Lucas, Paul Timpson# (2016) Intravital imaging reveals new ancillary mechanisms co-opted by cancer cells to drive tumor progressionF1000Research, 5(F1000 Faculty Rev):892. # corresponding author

Zahra Erami, David Herrmann, Sean C. Warren, Max Nobis, Ewan J. McGhee, Morghan C. Lucas, Wilfred Leung, Nadine Reischmann, Agata Mrowinska, Juliane P. Schwarz, Shereen Kadir, James R.W. Conway, Claire Vennin, Saadia A. Karim, Andrew D. Campbell, David Gallego-Ortega, Astrid Magenau, Kendelle J. Murphy, Rachel A. Ridgway, Andrew M. Law, Stacey N. Walters, Shane T. Grey, David R. Croucher, Lei Zhang, Herbert Herzog, Edna C. Hardeman, Peter W. Gunning, Chris J. Ormandy, T.R. Jeffry Evans, Douglas Strathdee, Owen J. Sansom, Jennifer P. Morton, Kurt I. Anderson# and Paul Timpson# (2016) Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue. Cell Reports 14, 152-67. # corresponding authors

Zahra Erami, Paul Timpson, Wu Yao, Ronen Zaidel-Bar, Kurt I. Anderson (2015) There are four dynamically and functionally distinct populations of E-cadherin in cell junctions. Biology Open

Jasreen Kular, Kaitlin G. Scheer, Natasha T. Pyne, Amr H. Allam, Anthony N. Pollard, Astrid Magenau, Rebecca L. Wright, Natasha Kolesnikoff, Paul A. Moretti, Lena Wullkopf, Frank C. Stomski, Allison J. Cowin, Joanna M. Woodcock, Michele A. Grimbaldeston, Stuart M. Pitson, Paul Timpson, Hayley S. Ramshaw, Angel F. Lopez, Michael S. Samuel (2015) A Negative Regulatory Mechanism Involving 14-3-3ζ Limits Signaling Downstream of ROCK to Regulate Tissue Stiffness in Epidermal Homeostasis. Developmental Cell. Dec 21;35(6):759-74. doi: 10.1016/j.devcel.2015.11.026.

Lisa M. Ooms, Lauren C. Binge, Elizabeth M. Davies, Parvin Rahman, James R.W. Conway, Rajendra Gurung, Daniel T. Ferguson, Antonella Papa, Clare G. Fedele, Jessica L. Vieusseux, Ryan C. Chai, Frank Koentgen, John T. Price, Tony Tiganis, Paul Timpson, Catriona A. McLean and Christina A. Mitchell (2015) The Inositol Polyphosphate 5-Phosphatase PIPP Regulates AKT1-Dependent Breast Cancer Growth and Metastasis. Cancer Cell Aug 10;28(2):155-69. doi: 10.1016/j.ccell.2015.07.003.

James R.W. Conway, Neil O. Carragher# and Paul Timpson# (2014) Developments in preclinical cancer imaging: innovating the discovery of therapeuticsNature reviews. Cancer 14, 314-328. # corresponding authors * received a F1000 prime 2-star recommendation.

David Herrmann, James R.W. Conway, Claire Vennin, Astrid Magenau, Will E. Hughes, Jen P. Morton and Paul Timpson# (2014) Three-dimensional cancer models mimic cell-matrix interactions in the tumour microenvironment. Carcinogenesis. # corresponding author

Iain R. Macpherson, Elena Rainero, Louise E. Mitchell, Peter V.E. van den Berghe, Claire Speirs, Marta A. Dozynkiewicz, Suman Chaudhary, Gabriela Kalna, Joanne Edwards, Paul Timpson and Jim C. Norman (2014) CLIC3 controls recycling of late endosomal MT1-MMP and dictates invasion and metastasis in breast cancer. J Cell Sci 127, 3893-3901.

Anna-Karin E. Johnsson, Yanfeng Dai, Max Nobis, Martin J. Baker, Ewan J. McGhee, Simon Walker, Juliane P. Schwarz, Shereen Kadir, Jennifer P. Morton, Kevin B. Myant, David J. Huels, Anne Segonds-Pichon, Owen J. Sansom, Kurt I. Anderson, Paul Timpson# and Heidi C.E. Welch# (2014) The Rac-FRET Mouse Reveals Tight Spatiotemporal Control of Rac Activity in Primary Cells and Tissues. Cell reports 6, 1153-1164. # corresponding authors

Meritxell Reverter, Carles RenteroAna Garcia-MeleroMonira HoqueSandra Vilà de MugaAnna Álvarez-GuaitaJames R.W. ConwayPeta WoodRose CairnsLilia LykopoulouDaniel GrinbergLluïsa VilageliuMarta BoschJoerg HeerenJuan BlasiPaul Timpson, Albert PolFrancesc TebarRachael Z. MurrayThomas GrewalCarlos Enrich (2014) Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries. Cell reports.

Max Nobis, Neil O. Carragher, Ewan J. McGhee, Jennifer P. Morton, Owen J. Sansom, Kurt I. Anderson and Paul Timpson# (2013) Advanced intravital sub-cellular imaging reveals vital 3D signalling events driving cancer cell behaviour and drug response in live tissueFEBS Journal 280(12):5177-97. # corresponding author

Max Nobis, Ewan J. McGhee, Jennifer P. Morton, Juliane P. Schwarz, Saadia A. Karim, Jean Quinn, Mike Edward, Andrew D. Campbell, Lynn C. McGarry, T.R. Jeffry Evans, Valerie G. Brunton, Margaret C. Frame, Neil O. Carragher, Yingxiao Wang, Owen J. Sansom, Paul Timpson# and Kurt I. Anderson# (2013) Intravital FLIM-FRET imaging reveals dasatinib-induced spatial control of Src in pancreatic cancer.  Cancer Research 73(15):4674-86. # corresponding author

Kevin B. Myant, Patrizia CammareriEwan J. McGheeRachel A. RidgwayDavid J. HuelsJulia B. CorderoSarah SchwitallaGabriela KalnaErinn-Lee OggDimitris AthineosPaul TimpsonMarcos VidalGraeme I. MurrayFlorian R. GretenKurt I. AndersonOwen J. Sansom (2013) ROS production and NF-kappaB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell stem cell 12, 761-773.

Paul Timpson#, Ewan J. McGhee, Jennifer P. Morton, Alex von Kriegsheim, Juliane P. Schwarz, Saadia A. Karim, Brendan Doyle, Jean A. Quinn, Neil O. Carragher, Mike Edward, Michael F. Olson, Margaret C. Frame, Valerie G. Brunton, Owen J. Sansom and Kurt I. Anderson (2011) Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53Cancer Research 71(3):747-57. # corresponding author

Paul Timpson, Ewan J. McGhee and Kurt I. Anderson (2011) Imaging molecular dynamics in vivo--from cell biology to animal models. J Cell Sci 124, 2877-2890.

Ewan J. McGhee, Jennifer P. Morton, Alex Von Kriegsheim, Juliane P. Schwarz, Saadia A. Karim, Neil O. Carragher, Owen J. Sansom, Kurt I. Anderson and Paul Timpson# (2011) FLIM-FRET Imaging In Vivo Reveals 3D-Environment Spatially Regulates RhoGTPase Activity During Cancer Cell InvasionSmall GTPases, 2(4):239-244. # corresponding author

Paul Timpson, Ewan J. McGhee, Zahra Erami, Jean A. Quinn, Mike Edward, and Kurt I. Anderson (2011) Organotypic collagen Ι assay: A malleable platform to assess cell behaviour in a 3-dimensional contextJ Vis Exp (56):e3089. 

Colin R. Lindsay, Samuel Lawn, Andrew D. Campbell, William J. Faller, Richard L. Mort, Florian Rambow, Paul Timpson, Ang Li, Rachel A. Ridgway, Jennifer P. Morton, Brendan Doyle, Mairin Rafferty, Ian G. Murphy, Enda W. McDermott, Kieran Sheahan, Katherine Pedone, Alexander J. Finn, Pamela A. Groben, Nancy E. Thomas, Honglin Hao, Craig Carson, William M. Gallacher, Ian J. Jackson,  Leon Van Kempen, Channing Der , Friedrich Beermann, Lionel Larue, Heidi C. Welch, Brad W. Ozanne, and Owen J. Sansom (2011) P-Rex1 is required for efficient melanoblast migration and melanoma metastasisNature Communications 2:555.

Michael Samuel, Jose Lopez, Ewan McGhee, Daniel Croft, David Strachan, Paul Timpson, June Munro, Ewald Schröder, Jing Zhou, Valerie Brunton, Nick Barker, Hans Clevers, Owen Sansom, Kurt Anderson, Valerie Weaver and Michael Olson (2011) Actomyosin-mediated cellular tension drives increased tissue stiffness and β-catenin activation to induce interfollicular epidermal hyperplasia and tumor growthCancer Cell 19(6): 776-91.

Jennifer Morton, Paul Timpson, Saadia A. Karim, Rachel A. Ridgway, Dimitris Athineos, Brendan D. Doyle, Nigel B. Jamieson, Karin A. Oien, Andy Lowy, Valerie G. Brunton, Margaret C. Frame, T.R. Jeffry Evans and Owen J. Sansom (2010) Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer.  PNAS USA 107(1): 246-51. * received a F1000 prime 2-star recommendation.

Jennifer Morton, Saadia Karim, Kathryn Graham, Paul Timpson, Nigel Jamieson, Susan Mason, Man-yeung Heung, Karin A. Oien, Margaret C. Frame, T.R. Jeffry Evans, Owen J. Sansom and Valerie G. Brunton (2010) Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinomaGastroenterology 139 (1):292-303.

Alan Serrels*, Paul Timpson*, Marta Canel, Juliane P Schwarz, Neil Carragher, Margaret C. Frame, Valerie G. Brunton and Kurt Anderson (2009) Real-time study of E-cadherin and membrane dynamics in living animals; implications for disease modelling and drug developmentCancer Research 69(7):2714-9. *co-first author. 

Paul Timpson, Ashleigh S. Wilson, Gillian M. Lehrbach, Robert L. Sutherland, Elizabeth A. Musgrove and Roger J. Daly (2007) Aberrant expression of cortactin in head and neck squamous cell carcinoma cells is associated with enhanced cell proliferation and resistance to the epidermal growth factor receptor inhibitor gefitinibCancer Research 67(19): 9304-14.

Paul Timpson, Danielle K. Lynch, Daniel Schramek, Francesca Walker, and Roger J. Daly (2005) Cortactin overexpression inhibits ligand-induced down-regulation of the epidermal growth factor receptor, Cancer Res 65, 3273-3280.

Paul Timpson, Gareth E. Jones, Margaret C. Frame and Valerie G. Brunton (2001) Coordination of cell polarization and migration by the Rho family GTPases requires Src tyrosine kinase activity, Curr Biol 11, 1836-1846.

Dr Paul Timpson