BV is Professor of Cell Signalling at the UCL Cancer Institute, London.
Following a PhD in the Laboratory of Molecular Biology at Ghent University (Belgium), BV carried out postdoctoral studies at the Ludwig Institute for Cancer Research, London where he was involved in a systematic effort to isolate the genes encoding PI 3-kinases (PI3Ks). This led to the realisation that PI3Ks form a family of enzymes. Together with his colleagues, BV proposed the now universally-accepted classification and nomenclature of PI3K isoforms.
The aim of his laboratory is to uncover the function and mechanism of action of the PI3K isoforms in normal physiology and disease, and to support efforts to therapeutically interfere with this pathway.
To achieve these aims, his laboratory generated the first-ever ‘kinase knockin’ mice, in which a kinase is inactivated by germline mutation of a conserved ATP-binding residue in the kinase-active site. This strategy provides a more adequate physiological model to study the effects of kinase-inhibitors compared to gene knock-out approaches. These mouse models have been highly predictive of PI3K-drug action in humans, including on-target toxicities, and have been extensively licenced to pharma industry for preclinical studies.
BV discovered the PI3Kdelta isoform of PI3K and with his team has taken its characterization ‘all the way’, from gene-cloning, through to the development of the first mouse models, uncovering this PI3K as a new drug target in immunity, haematological malignancies and, most recently, in solid tumours. This was followed by the generation of PI3Kdelta-inhibitors in a drug development programme with PIramed Ltd (acquired by Roche in 2008).
Targeting PI3Kdelta has been the most successful clinical PI3K-inhibitor development effort to date, culminating in the approval in 2014 of the PI3Kdelta-inhibitor idelasib/zydelig (Gilead) for the treatment of specific B-cell malignancies. Several inhibitors which differ in PI3K isoform-selectivity but share the ability to inhibit PI3Kδ are now approved for the treatment of specific B-cell malignancies.
Recent studies in collaboration with Klaus Okkenhaug, indicates that PI3Kdelta-inhibition, through preferential inhibition of immunosuppressive regulatory T-cells, leads to immunostimulation in cancer, potentially widening the use of PI3Kdelta-inhibitors from haematological malignancies to solid tumours. The concept of PI3Kdelta-inhibitor-driven cancer immunotherapy is currently being tested in various clinical trials.
Current research is focused on the biology of the PI3Kalpha and PI3Kdelta isoforms, and on the role of the PTEN tumour suppressor, including novel ways to control the biological activities of these key PI3K pathway regulators.
BV is an elected member of EMBO and of the UK Academy of Medical Sciences.