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

• 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

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) (2)
https://www.ncbi.nlm.nih.gov/pubmed/33146386

Withanolide Metabolites Inhibit PI3K/AKT and MAPK Pro-Survival Pathways and Induce Apoptosis in Acute Myeloid Leukemia Cells. Akhtar N, Baig MW, Haq I-U et al. Biomedicines (2020) 8(2)
https://www.ncbi.nlm.nih.gov/pubmed/32899914

The breast cancer oncogene IKKε coordinates mitochondrial function and serine metabolism Xu R, Jones W, Wilcz-Villega E et al. EMBO Reports (2020) 21(7)

Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer Gadaleta E, Fourgoux P, Pirró S et al. npj Breast Cancer (2020) 6(1)

A systematic molecular and pharmacologic evaluation of AKT inhibitors reveals new insight into their biological activity Kostaras E, Kaserer T, Lazaro G et al. British Journal of Cancer (2020) 123(7) 542-555

Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation. Patani H, Rushton MD, Higham J et al. Nat Commun (2020) 11(2) 3671
https://www.ncbi.nlm.nih.gov/pubmed/32699299

Cancer Burden Is Controlled by Mural Cell-β3-Integrin Regulated Crosstalk with Tumor Cells Wong PP, Muñoz-Félix JM, Hijazi M et al. Cell (2020) 181(7) 1346-1363.e21

Prediction of Signed Protein Kinase Regulatory Circuits. Invergo BM, Petursson B, Akhtar N et al. Cell Syst (2020) 10(2) 384-396.e9
https://www.ncbi.nlm.nih.gov/pubmed/32437683

Cancer associated fibroblast FAK regulates malignant cell metabolism. Demircioglu F, Wang J, Candido J et al. Nature Communications (2020) 11(1) 1290-1290
https://www.ncbi.nlm.nih.gov/pubmed/32157087

Liver Activation of Hepatocellular Nuclear Factor-4α by Small Activating RNA Rescues Dyslipidemia and Improves Metabolic Profile Huang KW, Reebye V, Czysz K et al. Molecular Therapy - Nucleic Acids (2020) 19(7) 361-370

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.