Dr Nick Leslie


Joining January 2013


Heriot-Watt University


EH14 4AS



Dr Nick Leslie and his laboratory study how the loss of control over cellular signal transduction mechanisms drive the development of many cancers, with a long term interest in the tumour suppressor and lipid phosphatase, PTEN. For some years, his group has studied the post-translational regulation of PTEN activity that is applied by phosphorylation, oxidation and ubiquitination of the enzyme. More recently, several projects are now using this detailed understanding of the PTEN protein to investigate how specific mutations that occur in human tumours drive the development of these cancers and whether this information can be used to improve cancer treatment.

Nick completed his first degree in Genetics at Cambridge University and a PhD at Glasgow University with David Sherratt, FRS. After PostDoctoral research with Paul Harrison at the Beatson Institute for Cancer Research, he moved to Dundee to work with Peter Downes and Philip Cohen at the inception of their pharmaceutical collaboration, the Division of Signal Transduction Therapy. It was in Dundee that Nick began studying the PI 3-kinase signalling pathway and PTEN. Nick was appointed as an Independent Investigator in 2002 and as an RCUK Academic Fellow in 2006. Most recently, Nick was appointed as a Reader at Heriot Watt University, and will move there with his research group at the end of 2012.


Cellular regulation and cancer

The normal regulation of processes including cell growth, survival, metabolism and migration in many cells relies on a control system called the PI 3-kinase/PTEN signalling pathway. Accordingly, loss of control over PI 3-Kinase signalling drives many types of cancer and is a characteristic of many other diseases, such as type 2 diabetes, which has motivated the development of many drugs to target the pathway for the treatment of these conditions. A project is available applying novel technology to develop a more detailed understanding of the activation of PI3K signalling in cancer.

Super-resolution analysis of the PI 3-Kinase pathway: Our recent work implicates localised PI3K signalling in driving many tumours (see eg Tibarewal et al, 2012). In collaboration with the laboratories of Prof Rory Duncan and Dr Colin Rickman, we will investigate these poorly understood tumorigenic mechanisms using super-resolution microscopy and through the development of novel high resolution signalling reporters.

Novel cancer models: investigating mechanism and treatment. We have developed new model systems to study the development and treatment in transgenic mice of cancers that develop due to mutational activation of the PI3K signaling pathway. We will be studying: 1. Mechanisms by which specific mutations in components of the PI3K pathway promote tumour development and 2. To study treatment options using drugs that target components of the PI3K pathway.

References: Tibarewal et al, 2012, Science Signaling, 5, ra18; Davidson et al, 2010, Oncogene, 29, 687; Leslie et al, 2007, Current Biol., 17, 115; Leslie and Foti, 2011, Trends Pharmacol. Sci., 32, 131.