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.
Activating mutations in BRAF disrupt the hypothalamo-pituitary axis leading to hypopituitarism in mice and humans Gualtieri A, Kyprianou N, Gregory LC et al. Nature Communications (2021) 12(7)
Drug ranking using machine learning systematically predicts the efficacy of anti-cancer drugs Gerdes H, Casado P, Dokal A et al. Nature Communications (2021) 12(7)
KDM5 inhibition offers a novel therapeutic strategy for the treatment of KMT2D mutant lymphomas Heward J, Konali L, D'Avola A et al. Blood (2021) 138(7) 370-381
Correction to 'Elucidation of the BMI1 interactome identifies novel regulatory roles in glioblastoma'. Freire-Benéitez V, Pomella N, Millner TO et al. NAR Cancer (2021) 3(2) zcab020
Predictive phosphoproteomic signatures for midostaurin plus chemotherapy response in FLT3 mutant positive acute myeloid leukaemia. Dokal AD, Arruda A, Smith R et al. Journal of Clinical Oncology (2021) 39(10) 7019-7019
Elucidation of the BMI1 interactome identifies novel regulatory roles in glioblastoma. Freire-Benéitez V, Pomella N, Millner TO et al. NAR Cancer (2021) 3(2) zcab009
His452Tyr polymorphism in the human 5-HT2A receptor affects clozapine-induced signaling networks revealed by quantitative phosphoproteomics. Martín-Guerrero SM, Alonso P, Iglesias A et al. Biochem Pharmacol (2021) 185(2) 114440
Sequence and Structure-Based Analysis of Specificity Determinants in Eukaryotic Protein Kinases. Bradley D, Viéitez C, Rajeeve V et al. Cell Rep (2021) 34(2) 108602
Rituximab and obinutuzumab differentially hijack the B-cell receptor and NOTCH1 signaling pathways. Edelmann J, Dokal AD, Vilventhraraja E et al. iScience (2021) (1) 102089-102089
PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability. Martín-Guerrero SM, Casado P, Hijazi M et al. Biochem J (2020) 477(2) 4491-4513
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.