Partners

Bart Vanhaesebroeck

Bart Vanhaesebroeck is Professor of Cell Signalling at the UCL Cancer Institute in London.
Following a PhD from Ghent University (Belgium), focusing on cytokine signalling and cell death, BV carried out postdoctoral studies with Mike Waterfield at the Ludwig Institute for Cancer Research, London where he was involved in the isolation of PI 3-kinase (PI3K) genes. These studies led to the realisation that PI3Ks form a family of related enzymes with potentially distinct roles in biology and disease.
In order to gain insight into the organismal roles of PI3K isoforms, we pioneered the use of ‘kinase knockin’ mice, in which a kinase is inactivated by mutation of a conserved ATP-binding residue in the kinase active site. This strategy provides a more adequate physiological model for the effects of small molecule kinase inhibitors than classical gene KO approaches.
These studies led to the discovery of the p110delta isoform of PI3K as a new drug target in inflammation, allergy, haematological malignancies and, most recently, in solid tumours. We have taken the characterization of p110delta ‘all the way’, from gene cloning, through to the development of the first mouse models, followed by the generation of p110delta inhibitors in a drug development programme with PIramed Ltd (purchased by Roche in 2008). Targeting p110delta has been the most successful clinical PI3K inhibitor development effort to date, which culminated in the approval in 2014 of the p110delta inhibitor Zydelig (Gilead Sciences Inc) for the treatment of specific blood cancers. p110delta inhibitors are also being trialled in arthritis and allergy.
Our recent work (Nature 2014:510:407), in collaboration with the laboratory of Klaus Okkenhaug in Cambridge, UK, indicates that p110delta could also be a target for immuno-stimulation in cancer, potentially widening the use of p110delta drugs from inflammation and haematological malignancies to immune-therapy of solid tumours.
BV is a member of EMBO and of the UK Academy of Medical Sciences.