Network Biology

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*, Han JZR*, Portmann N, Nobis M, Hastings JF, Murphy KJ, Latham SL, Cadell AL, Miladinovic D, Marriott G, O-Donnell YEI, Shearer RF, Williams J, Garcia Munoz A, Cox TR, Watkins DN, Saunders DN, Timpson P, Lim E, Kolch W, Croucher DR. (2019) Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer. Breast Cancer Research, 21(43).

Hastings JF, Skinhas JN, Fey D, Croucher DR*, Cox TR*. (2019) The extracellular matrix as a key regulator of intracellular signalling networks. British Journal of Pharmacology (Invited Review). * Corresponding Authors, 176(1):82-92.

Marini KD, Croucher DR, McCloy R, Gonzalez-Rajal A, Hastings JF, Jayasekara S, Alamgeer M, Boolell V, Vaghijiani V, Szczepny A, Han JZR, Waugh T, Lee HC, Oakes SR, Beena K, Harrison C, Lorensuhewa N, Kita B, Barrow R, Robinson BW, deKretser DM, Wu J, Ganju V, Burgess AJ, Martelotto LG, Rossello FJ, Cain JE, Watkins DN. (2018) Inhibition of Activin Signaling Increases the Therapeutic Index of Platinum Chemotherapy in Lung Adenocarcinoma. Science Translational Medicine, 10(451):eaat3504

Conway JRW, Warren SC, Herrmann D, Shearer RF, Killen M, Melenec P, Pinese M, Magenau A, Haigh JJ, Wang Y, Croucher DR, Sansom OJ, Pajic M, Morton JP, Timpson P. (2018) Intravital imaging to monitor therapeutic response in moving hypoxic regions resistant to PI3K pathway targeted therapies in pancreatic cancer. Cell Reports, 23(11): 3312-3326.

Rogers S, McCloy RA, Parker BL, Gallego-Ortega D, Law A, Chin VT, Conway J, Fey D, Krcic M, Deng N, Millar EKA, O’Toole S, Swarbrick A, Timpson P, Caldon CE, Croucher DR, James DE, Watkins DN, Burgess A. (2018) MASTL overexpression promotes chromosome instability and metastasis in breast cancer. Oncogene, 37: 4518–4533.

Hastings JF, Han JZR, Shearer RF, Kennedy SP, Iconomou M, Saunders DN, Croucher DR. (2018) Dissecting multi-protein signaling complexes by Bimolecular Complementation Affinity Purification (BiCAP). J. Vis. Exp. (136), e57109, doi:10.3791/57109 (2018).ss.

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, 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.

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.

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

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.

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

Monica Phimmachanh

Research Assistant

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