Group Leader: Professor Bart Vanhaesebroeck, PhD FMedSci
Our research focuses on the study of PI 3-kinases (PI3Ks). PI3Ks control signal transduction in cells, and are implicated in cancer, immune dysregulation, overgrowth syndromes and other disease conditions. Drugs that block PI3K action are now approved medicines, and more are in development.
The aims of our laboratory are to understand the mechanism of PI3K action in cells and organisms, and to facilitate PI3K targeting for clinical benefit. Over the years, our fundamental science studies have contributed to the initiation of drug development, clinical trials and drug approval, including with PI3Kdelta inhibitors in immune dysregulation, B-cell lymphoma and immunotherapy of solid tumours.
Publications: View full list of publications on PubMed.
Talks: For a general introduction to PI 3-kinase: see Vanhaesebroeck, B. (2020, August 31). PI 3-kinases and lipid messengers [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved September 3, 2020, from https://hstalks.com/bs/461/
For a PhD student video & pictures of the lab, see http://youtu.be/iXeUxp_h3Bw
Get in touch: We welcome informal enquiries - if you would like to work with us, please contact Bart Vanhaesebroeck email@example.com
Our laboratory covers 3 main lines of research:
1. PI3K isoform function: we aim to uncover the functions of the PI3K family members in normal physiology and in disease, and to understand their molecular mechanism of action. The main sponsors of this work are Cancer Research UK, the EU and the BBSRC.
2. PTEN Hamartoma Tumour Syndrome (PHTS): this is a human condition in which the PTEN gene is faulty, predisposing to overgrowth, autism-like spectrum and cancer. PTEN is an enzyme which keeps PI3K in check. We aim to understand how PTEN works in an organism, and to explore if PI3K inhibitors can be used to alleviate PHTS. The main sponsor of these studies is the PTEN Research Foundation.
3. Exploring alternative ways to interfere with PI3K signalling: this is a drug development programme, under the umbrella of the BRC Therapeutic Innovation Network (TIN). Bart V. is the co-Chair of the Small Molecule Therapeutic Innovation Network (TIN), launched in July 2018. The main sponsors of this work are UCL and the NIHR University College London Hospitals Biomedical Research Centre.
A highlight of our work to date is the discovery of PI3Kdelta, a PI3K family member that is highly expressed in white blood cells, as a drug target in various diseases. Our team has been involved in the characterization of PI3Kdelta ‘all the way’, from gene cloning through to the generation of the first mouse models and the development of PI3Kdelta inhibitors (by PIramed UK, acquired by Roche in 2008). Over the years, we have uncovered PI3Kdelta as a drug target in immunity, inflammation and haematological cancers and, most recently, as a target for cancer immunotherapy.
In 2014, a PI3Kdelta inhibitor (idelalisib from Gilead Sciences) was the first PI3K inhibitor to be approved, namely for the treatment of specific B-cell leukaemias. PI3Kdelta inhibitors also show great promise in the 'Activated PI3Kdelta Syndrome' (APDS), a disease due to germline activating mutations in the PI3Kdelta gene. Based on our finding that PI3Kdelta inhibition leads to the activation of the immune system against cancer (Nature 2016:535:580), PI3Kdelta inhibitors are now also being tested in cancer immunotherapy trials in solid tumours (see for example: Nature 2022:605:741 and ClinicalTrials.gov and iOnctura pipeline).