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 PI3K family members and to explore their potential as new drug targets for disease.

Our team discovered the PI3Kdelta 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 PI3Kdelta ‘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 PI3Kdelta 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 PI3Kdelta inhibitor (Zydelig - Gilead) was approved for the treatment of specific blood cancers.  Our discovery of the key role for PI3Kdelta in B-lymphocyte signalling (Science 2002:297:1031; Blood 2006:107:642) provides a molecular mechanism for the impressive clinical activity of PI3Kdelta inhibitors in some B-cell malignancies (Cancer Cell 2014:25:269).  Our work has also generated cell-based assays for PI3Kdelta drug development and for monitoring PI3Kdelta inhibitor activity in patients. Other than in cancer, PI3Kdelta 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).