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

The cytotoxic action of BCI is not dependent on its stated DUSP1 or DUSP6 targets in neuroblastoma cells Thompson EM, Patel V, Rajeeve V et al. FEBS Open Bio (2022) 12(7) 1388-1405

CKS1 inhibition depletes leukemic stem cells and protects healthy hematopoietic stem cells in acute myeloid leukemia Grey W, Rio-Machin A, Casado P et al. Science Translational Medicine (2022) 14(7)

LGG-44. Multi-omic analysis reveals integrated signalling networks in paediatric low-grade glioma Woodward L, Jones TA, Patel A et al. Neuro-Oncology (2022) 24(10) i98-i98

P405: INHIBITION OF CKS1-DEPENDENT PROTEOSTASIS REVEALS VULNERABILITIES IN LEUKAEMIC STEM CELLS WITH CONCOMITANT PROTECTION OF HEALTHY HAEMATOPOIETIC STEM CELLS Grey W, Rio-Machin A, Casado-Izquierdo P et al. HemaSphere (2022) 6(10) 305-306

eEF2K Activity Determines Synergy to Cotreatment of Cancer Cells With PI3K and MEK Inhibitors. Hijazi M, Casado P, Akhtar N et al. Mol Cell Proteomics (2022) 21(2) 100240
https://www.ncbi.nlm.nih.gov/pubmed/35513296

Suppression of Endothelial Cell FAK Expression Reduces Pancreatic Ductal Adenocarcinoma Metastasis after Gemcitabine Treatment Roy-Luzarraga M, Reynolds LE, de Luxán-Delgado B et al. Cancer Research (2022) 82(7) 1909-1925

Targeting the lysine-specific demethylase 1 rewires kinase networks and primes leukemia cells for kinase inhibitor treatment Pedicona F, Casado P, Hijazi M et al. Science Signaling (2022) 15(7)

BLOCKING ROR2 IMPROVES CARTILAGE INTEGRITY AND PROVIDES PAIN RELIEF IN OSTEOARTHRITIS, IN PART BY MODULATING YAP SIGNALLING Thorup A-S, Wilson J, Strachan D et al. Osteoarthritis and Cartilage (2022) 30(10) s159

Elucidating the role of the kinase activity of endothelial cell focal adhesion kinase in angiocrine signalling and tumour growth Newport E, Pedrosa AR, Lees D et al. Journal of Pathology (2022) 256(7) 235-247

Disruption of pancreatic stellate cell myofibroblast phenotype promotes pancreatic tumor invasion Murray ER, Menezes S, Henry JC et al. Cell Reports (2022) 38(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.