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Personal profile

Research interests

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.

Biography

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.

Research Group Contact Details

Fingerprint Fingerprint is based on mining the text of the person's scientific documents to create an index of weighted terms, which defines the key subjects of each individual researcher.

PTEN Phosphohydrolase Medicine & Life Sciences
Phosphoric Monoester Hydrolases Medicine & Life Sciences
Phosphatidylinositols Medicine & Life Sciences
1-Phosphatidylinositol 4-Kinase Medicine & Life Sciences
Lipids Medicine & Life Sciences
Phosphatidylinositol 3-Kinases Medicine & Life Sciences
Neoplasms Medicine & Life Sciences
Phosphoprotein Phosphatases Medicine & Life Sciences

Co Author Network Recent external collaboration on country level. Dive into details by clicking on the dots.

Research Output 1995 2018

  • 78 Article
  • 2 Chapter
  • 1 Chapter (peer-reviewed)
  • 1 Meeting abstract

A simple and robust real-time qPCR method for the detection of PIK3CA mutations

Alvarez Garcia, V., Bartos, C., Keraite, I., Trivedi, U., Brennan, P. M., Gharbi, K., Kersaudy-Kerhoas, M., Gharbi, K., Oikonomidou, O. & Leslie, N. R., 9 Mar 2018, In : Scientific Reports. 8, 4290

Research output: Contribution to journalArticle

Open Access
File
Mutation
Breast Neoplasms
High-Throughput Nucleotide Sequencing
DNA
Oligonucleotides

Identification of a PTEN mutation with reduced protein stability, phosphatase activity, and nuclear localization in Hong Kong patients with autistic features, neurodevelopmental delays, and macrocephaly

Wong, C. W., Or, P. M. Y., Wang, Y., Li, L., Li, J., Yan, M., Cao, Y., Luk, H. M., Tong, T. M. F., Leslie, N. R., Lo, I. F. M., Choy, K. W. & Chan, A. M. L., 2 Apr 2018, In : Autism Research.

Research output: Contribution to journalArticle

Open Access
File
Multiple Hamartoma Syndrome
Megalencephaly
Protein Stability
Phosphoprotein Phosphatases
Hong Kong

GSK3 and its interactions with the PI3K/AKT/mTOR signalling network

Hermida, M. A., Kumar, J. D. & Leslie, N. R., Aug 2017, In : Advances in Biological Regulation. 65, p. 5-15 11 p.

Research output: Contribution to journalArticle

Open Access
File
Phosphatidylinositol 3-Kinases
Phosphorylation
Glycogen Synthase Kinase 3
beta Catenin
Neurosciences

Importin-11 keeps PTEN safe from harm

Leslie, N. R., Mar 2017, In : Journal of Cell Biology. 216, 3, p. 539-541 3 p.

Research output: Contribution to journalArticle

Open Access
File
Karyopherins
PTEN Phosphohydrolase
Neoplasms
Lung

Prostate cancer, PI3K, PTEN and prognosis

Wise, H. M., Hermida Ayala, M. & Leslie, N. R., Feb 2017, In : Clinical Science. 131, 3, p. 197-210 14 p.

Research output: Contribution to journalArticle

Open Access
File
1-Phosphatidylinositol 4-Kinase
Prostatic Neoplasms
Phosphoric Monoester Hydrolases
Neoplasms
Biomarkers

Press / Media

Prostate cancer researchers receive £350,000 funding

Nicholas R. Leslie

22/05/15

1 media contribution

Press/Media: Research