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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.

The PTEN tumour supperssor : We have been studying the role of the different activities of PTEN, in particular why it can remoive phosphate groups from both lipid and protein substrates. We've also been trying to understyand why specific types of mutations in the tumour suppressor PTEN lead to different symptoms in individuals who inherit these mutations. 

3D Bioprinted cancer models: Having worked with 3D cell culture systems for many years, we have recently begun to develop 3D bioprinting methods to control the positioning of cancer cells, stromal cells and matrix components within tumour constructs. These projects, currently focusing on glioblastoma and pancreatic cancer, aim to provide new experimental models to study the tumour microenvironment and potentially for drug testing. 

References: Tibarewal et al, 2012, Science Signaling, 5, ra18; Leslie and Foti, 2011, Trends Pharmacol. Sci., 32, p131; Spinelli et al, 2015, J. Med Genet, 52, p128; Tabriz et al, 2015, Biofabrication, 7, 045012

Biography

Prof Nick Leslie and his laboratory have two related areas of research. Firstly, 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. Secondly, through collaborations with bioengineers, the group have been applying new technologies to cancer research, specifically using 3D bioprinting to develop new cultured cell models of cancer and also using microfluidics to enrich and detect cell free DNA in the circulation of cancer patients.

 

Nick completed his first degree in Genetics at Cambridge University and a PhD at Glasgow University with David Sherratt, FRS. After PostDoctoral research 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 there in 2002 and moved his lab to Heriot Watt University in  2013.

Research Group Contact Details

Fingerprint Dive into the research topics where Nicholas R. Leslie is active. These topic labels come from the works of this person. Together they form a unique fingerprint.

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
Neoplasms Medicine & Life Sciences
Phosphatidylinositol 3-Kinases 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 2019

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

Mechanisms of PTEN loss in cancer: it’s all about diversity

Álvarez-Garcia, V., Tawil, Y., Wise, H. M. & Leslie, N. R., 7 Feb 2019, In : Seminars in Cancer Biology.

Research output: Contribution to journalArticle

PTEN Phosphohydrolase
Neoplasms
Phosphatidylinositol 3-Kinases
Gene Silencing
Glioblastoma

PTEN Methylation by NSD2 Controls Cellular Sensitivity to DNA Damage

Zhang, J., Lee, Y-R., Dang, F., Gan, W., Menon, A. V., Katon, J. M., Hsu, C-H., Asara, J. M., Tibarewal, P., Leslie, N. R., Shi, Y., Pandolfi, P. P. & Wei, W., Sep 2019, In : Cancer discovery. 9, 9, p. 1306-1323 18 p.

Research output: Contribution to journalArticle

Methylation
DNA Damage
Phosphatidylinositol 3-Kinases
Heterografts
DNA

SWAP70 undergoes dynamic conformational regulation at the leading edge of migrating cells

Kriplani, N., Duncan, R. R. & Leslie, N. R., Feb 2019, In : FEBS Letters. 593, 4, p. 395-405 11 p.

Research output: Contribution to journalArticle

Monomeric GTP-Binding Proteins
Actins
Fluorescence Resonance Energy Transfer
Biosensing Techniques
Chemical activation

Three dimensional in vitro models of cancer: bioprinting multilineage glioblastoma models

Hermida, M. A., Kumar, J. D., Laverty, K. G., Di Bartolo, A., Ardron, M., Bogomolnijs, M., Clavreul, A., Brennan, P. M., Wiegand, U. K., Melchels, F., Shu, W. & Leslie, N. R., 17 Oct 2019, In : Advances in Biological Regulation. 100658.

Research output: Contribution to journalArticle

Bioprinting
Glioblastoma
Neoplasms
Printing
Stromal Cells

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

Press / Media

Prostate cancer researchers receive £350,000 funding

Nicholas R Leslie

22/05/15

1 Media contribution

Press/Media: Research