Contact: bart.vanh@qmul.ac.uk

Professional interests

Bart Vanhaesebroeck joined the Institute of Cancer from the Ludwig Institute for Cancer Research (University College London), to set up the Centre for Cell Signalling in June 2007.

Our key interest lies in understanding signalling through PI 3-kinases (PI3Ks), combining fundamental research with efforts to translate our findings into diagnostic and therapeutic applications.

In previous work, we proposed the now universally accepted classification and nomenclature of the PI3Ks (Philos Trans R Soc Lond 1996:351:217, TiBS 1997:22:267). We cloned the p110δ isoform of PI3K (PNAS 1997:94:4330), revealed p110d-selective functions in cells (Nat Cell Biol 1999:1:69; Cancer Res 2003:63:1667) and generated mouse models to investigate the in vivo function of this enzyme. We have pioneered the use of so-called 'kinase knockin' mice in which the active site carries a mutation in an ATP-binding amino acid residue, leading to inactivation of the kinase. These provide a more adequate physiological model for the effects of small molecule kinase inhibitors than classical gene knockout approaches (Cell 2004:118:274; TiBS 2005:30:194). Our recent studies have revealed key functions for p110d PI3K in adaptive immunity (Science 2002:297:1031), allergy (Nature 2004:431:1007) and leukaemia (Oncogene 2006:25:6648). Partly through these research efforts, p110d has become a drug target in cancer, inflammation and auto-immunity. Application of the mouse knockin strategy has allowed us to uncover the first physiological roles of the p110α isoform of PI3K (Nature 2006:441:366, Nature 2008;29:453) and p110β (PNAS 2008;105:8292) isoforms of PI3K. We are also developing novel methodologies to monitor the amount and activation of signal transduction enzymes, with focus on the PI3K pathway (PNAS 2006:103:8959, PNAS 2007:104:7809).

BV studied at the University of Ghent, Belgium, gaining a Masters degree (1985) in Biology (Physiology and Biochemistry) and a PhD (1990) in Molecular Biology. My PhD work, supervised by Drs. Walter Fiers and Johan Grooten, focused on immunology and signal transduction by cytokines. I then had to fulfill my military service which I carried out while working at University Hospital in Ghent in the Laboratories of Toxicology and Immunology. Following postdoctoral studies on signal transduction by Tumor Necrosis Factor, in the Laboratory of Molecular Biology in Ghent, and a brief stay at the University of Padova, Italy (with Professor Tulio Pozzan), I joined Mike Waterfield's group at the Ludwig Institute for Cancer Research in 1993 to work on PI 3-kinases. Since 1998, I have headed the Cell Signalling Group at the Ludwig Institute for Cancer Research, and in 2000, I was appointed as a Lecturer and in 2005 as a Professor at the Department of Biochemistry and Molecular Biology at University College London.

Research Team:

Dr Siemon Abraham	Technician
Dr Ezra Aksoy	Postdoctoral Research Assistant
Dr Pilar Alcolea	Postdoctoral Research Assistant
Dr Khaled Ali	Postdoctoral Research Assistant
Dr Samira Alliouachene	Postdoctoral Research Assistant
Miss Luisa Beltran	PhD Student
Dr Benoit Bilanges	Postdoctoral Research Assistan
Miss Ellie Burns	PhD Student
Dr Claire Chaussade	Postdoctoral Research Fellow
Dr Pedro Cutillas	Lecturer
Veronica Dominguez	Centre Administrator/PA
Dr Lazaros Foukas	Postdoctoral Research Fellow
Mr Cristiano Gonella	PhD Student
Dr Mariona Graupera	Postdoctoral Research Fellow
Dr Julie Guillermet-Guibert	Postdoctoral Research Fellow
Dr Inma Martin-Berenjeno	Postdoctoral Research Fellow
Mr Alexander Montoya	Technician
Mr Wayne Pearce	Biological Services Support Manager
Dr Vinothini Sivarajah	Postdoctoral Research Assistant
Dr Alex Sullivan	Lab Manager
Dr Salma Taboubi	Postdoctoral Research Assistant
Dr Neil Torbett	Postdoctoral Research Assistant
Prof Bart Vanhaesebroeck	Centre Lead
Miss Maria Whitehead	PhD Student

Recent Publications:

• Kok K, Nock GE, Verrall EA, Mitchell MP, Hommes DW, Peppelenbosch MP, Vanhaesebroeck B. Regulation of p110delta PI 3-kinase gene expression. PLoS ONE 2009;4(4):e5145.
• Kok K, Geering B, Vanhaesebroeck B. Regulation of phosphoinositide 3-kinas expression in health and disease. Trends Biochem Sci 2009;34(3):115-27.
• Billottet C, Banerjee L, Vanhaesebroeck B, Khwaja A. Inhibition of class I phosphoinositide 3-kinase activity impairs proliferation and triggers apoptosis in acute promyelocytic leukemia without affecting atra-induced differentiation. Cancer Res 2009;69(3):1027-36.
• Papakonstanti EA, Zwaenepoel O, Bilancio A, Burns E, Nock GE, Houseman B, Shokat K, Ridley AJ, Vanhaesebroeck B. Distinct roles of class IA PI3K isoforms in primary and immortalised macrophages. J Cell Sci 2008;121(Pt 24):4124-33.
• Bilanges B, Torbett N, Vanhaesebroeck B. Killing two kinase families with one stone. Nat Chem Biol 2008;4(11):648-9.
• Guillermet-Guibert J, Bjorklof K, Salpekar A, Gonella C, Ramadani F, Bilancio A, Meek S, Smith AJH, Okkenhaug K, Vanhaesebroeck B. The p110b isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110;γ. Proc Natl Acad Sci U S A 2008;105(24):8292-7
• Graupera M, Guillermet-Guibert J, Foukas LC, Phng LK, Cain RJ, Salpekar A, Pearce W, Meek S, Millan J, Cutillas PR, Smith AJ, Ridley AJ, Ruhrberg C, Gerhardt H, Vanhaesebroeck B. Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature 2008;453(7195):662-6.
• Ali K, Camps M, Pearce WP, Ji H, Rückle T, Kuehn N, Pasquali C, Chabert C, Rommel C, Vanhaesebroeck B. Isoform-Specific Functions of Phosphoinositide 3-Kinases: p110{delta} but Not p110{gamma} Promotes Optimal Allergic Responses In Vivo. J Immunol 2008;180(4):2538-44.
• Eickholt BJ, Ahmed AI, Davies M, Papakonstanti EA, Pearce W, Starkey ML, Bilancio A, Need AC, Smith AJ, Hall SM, Hamers FP, Giese KP, Bradbury EJ, Vanhaesebroeck B. Control of Axonal Growth and Regeneration of Sensory Neurons by the p110delta PI3-Kinase. PLoS ONE 2007;2(9):e869.
• Ji H, Rintelen F, Waltzinger C, Bertschy Meier D, Bilancio A, Pearce W, Hirsch E, Wymann MP, Rückle T, Camps M, Vanhaesebroeck B, Okkenhaug K, Rommel C. Inactivation of PI3Kgamma and PI3Kdelta distorts T-cell development and causes multiple organ inflammation. Blood 2007;110(8):2940-7.
• Papakonstanti EA, Ridley AJ, Vanhaesebroeck B. The p110delta isoform of PI 3-kinase negatively controls RhoA and PTEN. EMBO J 2007;26(13):3050-61.
• Cutillas PR, Vanhaesebroeck B. Quantitative profile of five murine core proteomes using label-free functional proteomics. Mol Cell Proteomics 2007;6(9):1560-73.
• Geering B, Cutillas PR, Nock G, Gharbi SI, Vanhaesebroeck B. Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimers. Proc Natl Acad Sci 2007;104(19):7809-14.
• Okkenhaug K, Patton DT, Bilancio A, Garcon F, Rowan WC, Vanhaesebroeck B. The p110delta isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cells. J Immunol 2006;177(8):5122-8.
• Cutillas PR, Khwaja A, Graupera M, Pearce W, Gharbi S, Waterfield M, Vanhaesebroeck B. Ultrasensitive and absolute quantification of the phosphoinositide 3-kinase/Akt signal transduction pathway by mass spectrometry. Proc Natl Acad Sci 2006;103(24):8959-64.
• Billottet C, Grandage VL, Gale RE, Quattropani A, Rommel C, Vanhaesebroeck B, Khwaja A. A selective inhibitor of the p110delta isoform of PI 3-kinase inhibits AML cell proliferation and survival and increases the cytotoxic effects of VP16. Oncogene 2006;25(50):6648-59.
• Foukas LC, Claret M, Pearce W, Okkenhaug K, Meek S, Peskett E, Sancho S, Smith AJ, Withers DJ, Vanhaesebroeck B. Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature 2006;441(7091):366-70.
• Bilancio A, Okkenhaug K, Camps M, Emery JL, Ruckle T, Rommel C, Vanhaesebroeck B. Key role of the p110delta isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110delta function in B cells. Blood 2006;107(2):642-50.
• Cutillas PR, Geering B, Waterfield MD, Vanhaesebroeck B. Quantification of gel-separated proteins and their phosphorylation sites by LC-MS using unlabeled internal standards: analysis of phosphoprotein dynamics in a B cell lymphoma cell line. Mol Cell Proteomics 2005;4(8):1038-51.
• Ali K, Bilancio A, Thomas M, Pearce W, Gilfillan AM, Tkaczyk C, Kuehn N, Gray A, Giddings J, Peskett E, Fox R, Bruce I, Walker C, Sawyer C, Okkenhaug K, Finan P, Vanhaesebroeck B. Essential role for the p110delta phosphoinositide 3-kinase in the allergic response. Nature 2004;431(7011):1007-11.
• Sawyer C, Sturge J, Bennett DC, O'Hare MJ, Allen WE, Bain J, Jones GE, Vanhaesebroeck B. Regulation of breast cancer cell chemotaxis by the phosphoinositide 3-kinase p110delta. Cancer Res 2003;63(7):1667-75.
• Okkenhaug K, Bilancio A, Farjot G, Priddle H, Sancho S, Peskett E, Pearce W, Meek SE, Salpekar A, Waterfield MD, Smith AJ, Vanhaesebroeck B. Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice. Science 2002;297(5583):1031-4.

Selected Reviews

• Okkenhaug K, Ali K, Vanhaesebroeck B. Antigen receptor signalling: a distinctive role for the p110delta isoform of PI3K. Trends Immunol 2007;28(2):80-7.
• Vanhaesebroeck B, Ali K, Bilancio A, Geering B, Foukas LC.  Signalling by PI3K isoforms: insights from gene-targeted mice. Trends Biochem Sci 2005;30(4):194-204.
• Okkenhaug K, Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol 2003;3(4):317-30.
• Okkenhaug K, Vanhaesebroeck B. New responsibilities for the PI3K regulatory subunit p85 alpha. Sci STKE 2001;2001(65):PE1.
• Vanhaesebroeck B, Leevers SJ, Ahmadi K, Timms J, Katso R, Driscoll PC, Woscholski R, Parker PJ, Waterfield MD.  Synthesis and function of 3-phosphorylated inositol lipids. Annu Rev Biochem 2001;70:535-602
• Vanhaesebroeck B, Alessi DR. The PI3K-PDK1 connection: more than just a road to PKB. Biochem J 2000;346 Pt 3:561-76.
• Vanhaesebroeck B, Waterfield MD. Signaling by distinct classes of phosphoinositide 3-kinases. Exp Cell Res 1999;253(1):239-54.
• Vanhaesebroeck B, Leevers SJ, Panayotou G, Waterfield MD. Phosphoinositide 3-kinases: a conserved family of signal transducers. Trends Biochem Sci 1997;22(7):267-72. 

<< Return to staff list