Network Biology


Many of the current generation of cancer therapeutics target components of signalling pathways, being either small molecule kinase inhibitors or monoclonal antibodies to cell surface receptors. Whilst these individual proteins and pathways represent attractive therapeutic targets, it is fast becoming apparent that the inherent flexibility of signalling pathways mean that targeting a single pathway component can lead to rapid network adaptation and the emergence of a resistant sub-population of tumour cells.

The Network Biology research group focuses on the investigation of network level aberrations induced by oncogenes and oncogenic mutations, ultimately aiming to elucidate how these altered network states lead to therapeutic resistance.

Selected Publications

Kennedy SP, Hastings JF, Han JZR, Croucher DR. (2016) The under-appreciated promiscuity of the epidermal growth factor receptor family. Frontiers in Cell and Developmental Biology, 4:88.

Croucher DR#, Iconomou M, Hastings JF, Kennedy SP, Han JZR, Shearer R, McKenna J, Wan A, Lau J, Aparicio S, Saunders DN#.  (2016) Bimolecular complementation affinity purification (BiCAP) reveals dimer-specific protein interactions for ERBB2 dimers. Science Signaling9(436), ra69.

Rogers S, Fey D, McCloy RA, Parker BL, Mitchell NJ, Payne RJ, Daly RJ, James DE, Watkins DN, Croucher DR, Burgess A. (2016) PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells. Journal of Cell Science, 129(7):1340-1354.

Erami Z*, Herrmann D*, Warren SC, Nobis M, McGhee EJ, Lucas M, Leung W, Reischmann N, Mrowinska A, Schwarz J, Kadir S, Conway JRW, Vennin C, Karim SA,  Campbell AD, Gallego-Ortega D, Magenau A, Murphy KJ, Ridgway RA, Law AM, Walters SN, Grey ST, Croucher DR, Zhang L, Herzog H, Hardeman EC, Gunning PW, Ormandy CJ, Jeffry Evans TR, Strathdee D,  Sansom , Morton JP, Anderson KI*, 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(1), 152-167.

Fey D, Kolch W, Kholodenko BN, Croucher DR. (2016) Cell Systems Call – Principles in Systems Biology, No. 1. ‘Signaling Pathway Models as Biomarkers’. Cell Systems, 2(1), 2-4.

Fey D, Halasz M, Dreidax D, Kennedy SP, Hastings JF, Rauch N, Garcia Munoz A, Pilkington R, Fischer M, Westermann F, Kolch W, Kholodenko BN, Croucher DR. (2015) Signaling pathway models as biomarkers: Patient-specific simulations of JNK activity predict the survival of neuroblastoma patients. Science Signaling, 8(408), ra130.

Duffy FJ, Devocelle M, Croucher DR, Shields DC (2014). Computational Survey of Peptides Derived from Disulphide-Bonded Protein Loops That May Serve as Mediators of Protein-Protein Interactions. BMC Bioinformatics15 (1), 305.

Freeman R, Niego B, Croucher DR, Ostergaard Pedersen L, Medcalf RL. (2014) t-PA, but not desmoteplase, induces plasmin-dependent opening of a blood brain barrier model under normoxic and ischaemic conditionsBrain Research1565:63-73.

Zheng Y, Zhang C, Croucher DR, Soliman MA, Bagshaw R, Pasculescu A, St-Denis N, Taylor L, Tate SA, Hardy RW, Colwill K, Dennis JW, Dai AY, Gingras A, Daly RJ, Pawson T (2013). Temporal regulation of EGF signaling networks by the scaffold protein Shc1. Nature, 499(7457): 166-171.

Croucher DR, Hochgräfe F, Zhang L, Liu L, Lyons RJ, Rickwood D, Tactacan CM, Browne BC, Ali N, Chan H, Shearer RF, Gallego-Ortega D, Saunders DN, Swarbrick A, Daly RJ (2013). Involvement of Lyn and the Atypical Kinase SgK269/PEAK1 in a Basal Breast Cancer Signaling Pathway. Cancer Research, 73(6): 1969-1980.

Ortiz Padilla C, Browne BC, Hochgräfe F, Caldon CE, Lyons RJ, Croucher DR, Rickwood D, Brummer T, Daly RJ (2013). Functional characterization of cancer-associated Gab1 mutations. Oncogene, 32(21): 2696-2702.

Fey D, Croucher DR, Kolch W, Kholodenko BN. (2012) Crosstalk and signalling switches in mitogen-activated protein kinase cascades. Frontiers in Physiology, 3:355.

Nguyen LK*, Matallanas D*, Croucher DR*, von Kriegsheim A*, Kholodenko BN (2012). Signalling by protein phosphatases and drug development: a systems-centred view. FEBS Journal, 280(2):751-65. *These authors all contributed equally

Cochran BJ, Croucher DR, Lobov S, Saunders DN, Ranson M (2011).   Dependence on endocytic receptor binding via a minimal binding motif underlies the differential prognostic profiles of serpinE1 and serpinB2 in cancer. Journal of Biological Chemistry, 286(27):24467-75.

Hochgräfe F, Zhang L, O’Toole S, Browne BC, Pinese M, Porta Cubas A, Lehrbach GM, Croucher DR, Rickwood D, Boulghourjian A, Shearer R, Nair R, Swarbrick A, Faratian D, Mullen P, Harrison DJ, Biankin AV, Sutherland RL, Raftery MJ, Daly RJ (2010). Tyrosine phosphorylation profiling reveals the signaling network characteristics of basal breast cancer cells. Cancer Research, 70(22): 9391-401.

Lee JA, Croucher DR, Ranson M (2010). Differential endocytosis of tissue plasminogen activator by plasminogen activator inhibitors type-1 and 2 on human peripheral blood monocytes. Thrombosis and Haemostasis, 104(6): 1133-42.

Croucher DR, Rickwood D, Tactacan CM, Musgrove EA, Daly RJ (2010). Cortactin modulates RhoA activation and expression of Cip/Kip cyclin dependent kinase inhibitors to promote cell cycle progression in 11q13-amplified head and neck squamous cell carcinoma cells. Molecular and Cellular Biology, 30(21): 5057-70.

Abdipranoto A, Park JS, Croucher DR, Daniel J, Henshall S, Galbraith S, Mervin K, Vissel B. (2009) Activin A Is Essential for Neurogenesis Following Neurodegeneration. Stem Cells. 27(6):1330-1346.

Samson AL, Nevin ST, Croucher D, Niego B, Daniel PB, Weiss TW, Moreno E, Monard D, Lawrence DA, Medcalf RL. (2008) Tissue-type plasminogen activator requires a co-receptor to enhance N-Methyl-D-Aspartate receptor function. Journal of Neurochemistry. 107(4):1091-1101.

Cao XR, Lill NL, Boase N, Shi PP, Croucher DR, Shan H, Qu J, Sweezer EM, Place T, Kirby PA, Daly RJ, Kumar S, Yang B. (2008) Nedd4 controls animal growth by regulating IGF-I signaling. Science Signaling. 1(38):ra5.

Croucher DR, Saunders DN, Lobov S, Ranson M. (2008) Revisiting the Biological Roles of PAI-2 (SerpinB2) in Cancer.  Nature Reviews Cancer. 8(7):535-45.

Croucher DR, Saunders DN, Stillfried GE, Ranson M. (2007) A Structural Basis for Differential Cell Signaling by PAI-1 and PAI-2 in Breast Cancer cells. Biochemical Journal. 408(2):203-10.

Croucher D, Saunders DN, Ranson M. (2006) The PAI-2:uPA Complex: A New Ligand for the Lipoprotein Receptor-Related Protein (LRP). Journal of Biological Chemistry. 281(15):10206-10213.

More Garvan Publications

Staff in the Group

Antonia Cadell

Research Assistant

Jeremy Han

PhD Student

Jordan Hastings

PhD Student

Dr Sharissa Latham

Research Officer

Yolande O'Donnell

Research Assistant

Monica Phimmachanh

Research Assistant

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