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Prof Bart Vanhaesebroeck
Cell Signalling - UCL Cancer Institute
Paul O'Gorman Building
72 Huntley Street
London
WC1E 6BT
Appointment
  • Professor of Cell Signalling
  • Research Department of Oncology
  • Cancer Institute
  • Faculty of Medical Sciences
Biography

Following a PhD (1995) from the Laboratory of Molecular Biology at Ghent University, Belgium (with Johan Grooten and Walter Fiers), BV carried out Postdoctoral studies at the Ludwig Institute for Cancer Research (with Mike Waterfield, FRS) at University College London (UCL), supported by a long-term Career Development Award from the NFWO (Belgian National Science Foundation; now: FWO, Fonds voor Wetenschappelijk Onderzoek, Flanders).

BV became Professor at UCL in 2005, and moved to Barts Cancer Institute, Queen Mary University of London in 2007.  In 2014, BV became Professor of Cell Signalling at the UCL Cancer Institute.


Research Summary

We study PI 3-kinase (PI3K) enzymes, which regulate signal transduction inside cells. PI3K signalling is overactive in cancer, overgrowth syndromes, inflammatory disorders and auto-immunity. Many PI3K inhibitors are in clinical development.


Our laboratory combines basic research with efforts to translate these findings into therapeutic applications. Our overall aim is to understand the roles of the 8 PI3K family members and to explore their potential as new drug targets for disease.


Our team discovered the p110delta family member of PI3K as a new target in immunity, inflammation and haematological malignancies and most recently, in collaboration with the group of Klaus Okkenhaug, as a target for cancer immunotherapy (Nature 2014:509:407).  We have taken the characterization of p110delta ‘all the way’, from gene cloning (PNAS 1997:94:4330), through to the development of the first mouse models (Science 2002:297:1031; Nature 2004:431:1007), allowing to discover the key roles of p110delta in the organism and in cells, followed by the development of p110delta inhibitors (with PIramed UK [acquired by Roche]), Intellikine [acquired by Infinity]) and other pharma) and, more recently, human studies.


In 2014, a p110delta inhibitor (Zydelig - Gilead) was approved for the treatment of specific blood cancers.  Our discovery of the key role for p110delta in B-lymphocyte signalling (Science 2002:297:1031; Blood 2006:107:642) provides a molecular mechanism for the impressive clinical activity of p110delta inhibitors in some B-cell malignancies (Cancer Cell 2014:25:269).  Our work has also generated cell-based assays for p110delta drug development and for monitoring p110delta inhibitor activity in patients. Other than in cancer, p110delta inhibitors are also being trialled in airway inflammation and arthritis.

Together with Klaus Okkenhaug, Andrew J. Smith and Austin Smith, we created the first  kinase-dead 'knock-in' mice (Science 2002:297:1031). In these mice, the active site of the kinase carries a mutation in an ATP-binding amino acid residue, leading to inactivation of the kinase. These provide a more suitable physiological model for the effects of small molecule kinase inhibitors than classical gene knockout approaches. We have used this technology to generate the largest complement of mutant PI3K mice world-wide. These mice have allowed us to discover the physiological roles of individual PI3K family members (Science 2002:297:1031; Nature 2004:431:1007; Nature 2006:441:366; Nature 2008:453:662), and have been extensively licenced to Pharma for preclinical studies to model PI3K inhibitors.

BV is an elected member of EMBO and the UK Academy of Medical Sciences. In 2010, together with Pedro Cutillas, BV set up Activiomics [acquired by hVIVO in 2014], to develop biomarkers in disease. The main funders of our research (past & current) are the Ludwig Institute for Cancer Research, Cancer Research UK, BBSRC, MRC, EU and the UCL Biomedical Research Centre (BRC).

Academic Background
1990 PhD Doctor of Philosophy – Molecular Biology Universiteit Gent
1985 LIC Licentiate – Biology, Physiology and Biochemistry Universiteit Gent
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