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Group Leader: Professor Bart Vanhaesebroeck, PhD FMedSci FRSB FRS
We study signal transduction in cells. We focus on the PI3K signalling molecules which are overactive in cancer, some immune contexts and in overgrowth syndromes. We aim to understand PI3K action and exploit this knowledge for therapy. Over the years, our studies have contributed to PI3K drug development, clinical trials and drug approval.
A highlight of our work to date is the discovery of PI3Kdelta, a PI3K family member that is highly expressed in white blood cells. PI3Kdelta inhibitors are now approved for some B-cell malignancies and are being tested in cancer immunotherapy, including in melanoma and lung cancer (see section on PI3Kdelta on this site).
After a long focus of inhibiting PI3Ks, we are now developing compounds to activate PI3K, the first study on which was published recently (rdcu.be/dcUpi). This work is in collaboration with Roger Williams at the MRC-LMB in Cambridge and AstraZeneca Open Innovation. In preclinical studies, these compounds can protect cardiac and neural tissue from the sort of damage seen in heart attack and stroke, and also stimulate nerve regeneration after injury. Paradoxically, such compounds may also be useful in cancer, by over-activating cell signalling (‘too much of a good thing’).
Publications: View full list of publications on PubMed.
Talks: For a general introduction to PI 3-kinase and lipid messengers: https://hstalks.com/bs/461/
Videos of the lab & staff:
- Life as PhD student in the CellSig lab - http://youtu.be/iXeUxp_h3Bw
- 30 years in research - https://www.medchemexpress.com/webinar-Bart.html
- An example of an EU-funded PhD Training Network - https://www.youtube.com/watch?v=02Kdk9D5Y3g
- On our successful collaboration with AstraZeneca Open Innovation - https://openinnovation.astrazeneca.com/success_stories.html
- Royal Society election June 2024 (Dutch/English) - https://shorturl.at/0r6hH
Get in touch: We welcome informal enquiries - if you would like to work with us, please contact Bart Vanhaesebroeck bart.vanh@ucl.ac.uk
The main funders of our research (past & current) are the Ludwig Institute for Cancer Research, Cancer Research UK, UKRI (BBSRC, MRC), EU and the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre.
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 UKRI.
2. PTEN Hamartoma Tumour Syndrome (PHTS): this is a human condition in which the PTEN tumour suppressor 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. Development of PI3K activators: Situations exist in which it would be useful to have PI3K activators. Examples are wound healing, nerve regeneration, stroke and cardioprotection, conditions in which PI3K is known to transmit regenerative and protective signals into the cells. PI3K activators could also be used to boost the immune response, and to stimulate cells in the brain to repair neuro-degenerative damage. Paradoxically, cells with too much PI3K, such as cancer cells, can also be destroyed by PI3K overactivation (‘too much of a good thing’).
