Since 2014: Professor of Cell Signalling at the UCL Cancer Institute.
- PhD: Laboratory of Molecular Biology, Ghent University, Belgium – Prof Johan Grooten and Prof. Walter Fiers
- Postdoc: Ludwig Institute for Cancer Research, London – Prof Michael Waterfield, FRS
- First Group Leader position: Ludwig Institute for Cancer Research, London (1998)
- Professor at UCL (2005-2007) and Barts Cancer Institute, Queen Mary University of London (2007-2013)
- Elected member of EMBO and the UK Academy of Medical Sciences
I received my PhD training when molecular biology technology, for the first time, allowed the isolation of human genes. This was a fascinating era, with my PhD Laboratory being at the forefront of cloning genes that regulate the immune system and cell survival (such as interleukins, tumour necrosis factor and others). Some of these gene products were very quickly progressed to clinical trials, especially in cancer. This time was also the start of the biotech industry, with many of my lab colleagues becoming involved in spin-out companies in the biomedical sector. This all meant that, very early during my training, I was exposed to what is now called ‘translational research’. This has been very formative for my subsequent research career, in which I have always tried to translate basic science findings into diagnostic and therapeutic applications.
After my PhD, I joined the laboratory of Mike Waterfield, FRS at the Ludwig Institute for Cancer Research in London. The groups of Mike and Peter Parker (now at the Crick Institute) had just isolated the gene for PI3Kalpha, a signal transduction protein implicated in cancer. PI3Kalpha turned out to be a member of a larger family of enzymes, called PI3Ks, the genes of many of which we cloned and characterised while in Mike’s group. This also allowed Mike’s group to suggest a general classification of the PI3K family members, which is now generally accepted. Over the last decade, the PI3K pathway has become a hot target in drug development, with PI3K inhibitors in clinical development in cancer, inflammatory disorders, auto-immunity and allergy.
I gambled my career on PI3Kdelta, a PI3K family member that I found to be highly expressed in leukocytes. My team has been involved in the characterization of PI3Kdelta ‘all the way’, from gene cloning, through to the generation of the first mouse models that allowed us to discover the roles of PI3Kdelta in the organism and in cells, and the development of PI3Kdelta inhibitors by PIramed UK (acquired by Roche in 2008), Intellikine (acquired by Infinity) and other Pharma. Over the years, we have uncovered PI3Kdelta as a drug target in immunity, inflammation and haematological malignancies and, most recently, in an effort led by Khaled Ali in the lab (now at Amgen), in collaboration with Klaus Okkenhaug (Cambridge) and Genentech (San Francisco, US), as a target for cancer immunotherapy in solid tumours.
In 2014, a PI3Kdelta inhibitor (Zydelig from Gilead Sciences) was the first PI3K inhibitor to be approved, namely for the treatment of specific blood cancers. PI3Kdelta inhibitors are also being trialled in airway inflammation, in the latter condition as an inhaled PI3Kdelta inhibitor. Our most recent finding that PI3Kdelta inhibition leads to immunostimulation in cancer has now also led to clinical trials, the first one of which will be in head and neck cancer (in a collaboration between CRUK, Amgen (San Francisco) and Christian Ottensmeier and his team at the Southampton CRUK Centre). Incyte has also initiated trials with PI3Kdelta inhibitors in combination with anti-PD1 checkpoint antibody (Pembrolizumab) in a range of advanced solid tumour indications.
Alongside my basic research, in 2010, I set up (together with Pedro Cutillas at Queen Mary University London) the mass-spectrometry-based spin-out company Activiomics to develop biomarkers in disease. Activiomics was acquired by Retroscreen (now hVIVO) in 2014.
The main funders of our research (past & current) are the Ludwig Institute for Cancer Research, Cancer Research UK, BBSRC, MRC, EU and the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre.