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-)
• Co-founder and Director, Kinomica Ltd (2016-)
• Member of the Steering Committee of The London Biological Mass Spectrometry Discussion Group (LBMSDG)
• Co-founder and Director, Activiomics Ltd (2011-2014)

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

Extracellular matrix educates an immunoregulatory tumor macrophage phenotype found in ovarian cancer metastasis Puttock EH, Tyler EJ, Manni M et al. Nature Communications (2023) 14(7)

Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes Casado P, Rio-Machin A, Miettinen JJ et al. Signal Transduction and Targeted Therapy (2023) 8(7)

S124: PHOSPHOPROTEOMICS ACCURATELY PREDICTS RESPONSES TO MIDOSTAURIN PLUS CHEMOTHERAPY IN TWO INDEPENDENT COHORTS OF FLT3 MUTANT-POSITIVE ACUTE MYELOID LEUKAEMIA Dokal A, Borek WE, Nobre L et al. HemaSphere 7(10) e3920765

Community detection in empirical kinase networks identifies new potential members of signalling pathways De Los Angeles Colomina Basanta C, Bazzi M, Hijazi M et al. PLoS Computational Biology (2023) 19(7)

Identification of novel phosphoproteomic biomarkers in patients with advanced hepatocellular carcinoma (HCC). Sarker D, Pedicona F, Zen Y et al. Journal of Clinical Oncology (2023) 41(10) e15155-e15155

In Silico Analysis Predicts Nuclear Factors NR2F6 and YAP1 as Mesenchymal Subtype-Specific Therapeutic Targets for Ovarian Cancer Patients Kassuhn W, Cutillas PR, Kessler M et al. Cancers (2023) 15(7)

Phosphoproteomics analysis of aryl hydrocarbon receptor interacting protein (AIP) knockout cells reveals AIP-mediated kinase signalling cascades Barry S, Haworth O, Rajeeve V et al. Endocrine Abstracts (10)

Abstract 5841: Exploring the role of versican in immune exclusion within triple negative breast cancer Hirani P, Alonge KM, Pennington DJ et al. Cancer Research (2023) 83(10) 5841-5841

HDAC Inhibition Restores Response to HER2-Targeted Therapy in Breast Cancer via PHLDA1 Induction Clayton NS, Carter EP, Fearon AE et al. International Journal of Molecular Sciences (2023) 24(7)

Proteomic Characterization of Acute Myeloid Leukemia for Precision Medicine Casado P, Cutillas PR Molecular and Cellular Proteomics (2023) 22(7)

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.

I am part of the Programme Team for the Cancer Genomics & Data Sciences MSc Programme at BCI, Queen Mary University of London.