My research group uses unique proteomics and computational approaches to understand how cell signalling pathways driven by the activity of protein kinases contribute to the development of cancer. Increasing this knowledge will be invaluable in advancing personalised cancer therapies.
Proteomic and genomic integration identifies kinase and differentiation determinants of kinase inhibitor sensitivity in leukemia cells. Leukemia (2018) 32(8):1818-22. PMID: 29626197
Empirical inference of circuitry and plasticity in a kinase signaling network. PNAS(2015) 112(25):7719-24. PMID: 26060313
Kinase-Substrate Enrichment Analysis provides insights into the heterogeneity of signaling pathway activation in leukemia cells. Science Signaling (2013) 3: rs6 PMID: 23532336
Phosphoproteomic analysis of leukemia cells under basal and drug-treated conditions identifies markers of kinase pathway activation and mechanisms of resistance. Mol Cell Proteomics (2012) 11(8):453-66. PMCID: PMC3412974.
I am interested in understanding how cell signalling pathways driven by the activity of protein kinases contribute to the development of cancer. Signalling pathways do not work in isolation but form a complex network of biochemical reactions that integrate extracellular signals into a coordinated cell biological response.
Essentially all cancers deregulate one or several components of this biochemical network, but unfortunately, cancers are heterogeneous in the way signalling is perturbed. In practice, this means that novel targeted therapies against signalling nodes do not work equally well in all patients. Even those patients that initially respond eventually develop resistance.
To understand the mechanisms underlying this heterogeneity, I developed methodology based on a technique named mass spectrometry and on computational science. These techniques can be used to measure how the signalling network is wired in individual cancer populations in a comprehensive and unbiased manner.
My group is now using these unique resources to investigate the fundamental properties of signalling networks and to understand how signalling heterogeneity in cancer (with particular focus on haematological malignancies) contribute to intrinsic and acquired resistance to compounds that target signalling enzymes.
Perineural invasion in pancreatic cancer: proteomic analysis and in vitro modelling. Alrawashdeh W, Jones R, Dumartin L et al. Mol Oncol (2019) 13(2) 1075-1091
Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion. Arnandis T, Monteiro P, Adams SD et al. Dev Cell (2018) 47(2) 409-424.e9
Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility. Angulo-Urarte A, Casado P, Castillo SD et al. Nat Commun (2018) 9(2) 4826
Shedding of bevacizumab in tumour cells-derived extracellular vesicles as a new therapeutic escape mechanism in glioblastoma. Simon T, Pinioti S, Schellenberger P et al. Mol Cancer (2018) 17(2) 132
Proteomic and genomic integration identifies kinase and differentiation determinants of kinase inhibitor sensitivity in leukemia cells. Casado P, Wilkes EH, Miraki-Moud F et al. Leukemia (2018) 32(2) 1818-1822
Genome instability is a consequence of transcription deficiency in patients with bone marrow failure harboring biallelic ERCC6L2 variants. Tummala H, Dokal AD, Walne A et al. Proc Natl Acad Sci U S A (2018) 115(1) 7777-7782
PHLDA1 Mediates Drug Resistance in Receptor Tyrosine Kinase-Driven Cancer. Fearon AE, Carter EP, Clayton NS et al. Cell Rep (2018) 22(2) 2469-2481
Proteomic and genomic integration identifies kinase and differentiation determinants of kinase inhibitor sensitivity in leukemia cells. Casado P, Wilkes EH, Miraki-Moud F et al. Leukemia (2017) (2)
Deconstruction of a metastatic tumor microenvironment reveals a common matrix response in human cancers. Pearce OMT, Delaine-Smith R, Maniati E et al. Cancer Discov (2017) (1)
Approaches to identify kinase dependencies in cancer signalling networks. Dermit M, Dokal A, Cutillas PR FEBS Lett (2017) 591(2) 2577-2592
I graduated with a PhD in 2004 from UCL. My studies (completed in the laboratories of Prof Mike Waterfield, Prof Rainer Cramer and Prof Al Burlingame) were on a project that investigated kidney physiology and were supervised by Prof Robert Unwin. I then completed postdoctoral training at the Ludwig Institute for Cancer Research (UCL branch).
In 2007, I became lecturer at the Centre for Cell Signalling and in 2010 I was promoted to Senior Lecturer. After a period in the MRC Clinical Sciences Centre (2012-2013), where I was Head of the Mass Spectrometry and Proteomics, I joined the Centre for Haemoto-Oncology in 2013 where I now lead the Integrative Cell Signalling and Proteomics Group.