Research

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.

Other Activities

• Turing Fellow (2018-)
• Founding Director, Activiomics Ltd (2011-2014)
• Member of the Steering Committee of The London Biological Mass Spectrometry Discussion Group (LBMSDG)

Major Funding

• 2020-2023 - Blood Cancer UK, Signalling pathways that determine responses of AML cells to FLT3 inhibitors, £245,281
• 2018-2022- MRC Medical Research Council, Translational Biology iCASE Programme - Grant, £202,131.99
• 2017-2021- CRUK, £350,000
• 2017-2019- Barts Charity, Proteomics mass spectrometry for the Barts Post-Genomic Phenotype Unit, £371,000
• 2015-2018- B.B.S.R.C., Systematic classificiation of phosphorylation sites for an integrative analysis of kinase signalling, £374,677
• 2015-2017- Barts Charity, Personalizing cancer treatments, £475,828
  
  

Recent Publications

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
https://www.ncbi.nlm.nih.gov/pubmed/34319293

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
https://www.ncbi.nlm.nih.gov/pubmed/34316702

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
https://www.ncbi.nlm.nih.gov/pubmed/33539816

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
https://www.ncbi.nlm.nih.gov/pubmed/33440154

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
https://www.ncbi.nlm.nih.gov/pubmed/33146386

Team

Postdoctoral Researchers

Biography

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.