Targeting Wnt Signalling in Skin Cancer

Wnt signalling was first discovered in tumour models and has been recognized as a key regulator in cancer for several decades. This has prompted a number of researchers and pharmaceutical companies to develop Wnt-modulating drugs for cancer treatment. However, we are still learning about the complex and often context-dependent effects of WNT signalling in differing tumour types, so it is important to understand the role of Wnt signalling in individual cancers before Wnt-modulating therapeutics can be used to treat patients. Skin cancer is more common than the combined incidence of breast, lung, prostate and colon cancer, where the annual incidence rates of skin cancer have been increasing for the past 3 decades, and highlights the need for urgent new treatments. Skin cancer can be broadly divided into two types; malignant melanoma (MM) derived from the pigment producing cells of the skin and non-melanoma skin cancer derived from keratinocytes (the predominant cell type of the epidermis), where non-melanoma skin cancers also comprise of two types; basal cell carcinoma and cutaneous squamous cell carcinoma (cSCC).

We and others have been studying the role of Wnt signalling in MM for a number of years now [1-4], which has led to a better understanding of how these signalling pathways control the progression of melanoma. However for other skin cancers (in particular cSCC), the understanding of how hyperactive Wnt signalling pathways affect disease progression are currently poorly investigated. Approximately one quarter of all skin-cancer related deaths are due to cSCC, highlighting a need for improved therapies to treat the disease. The aim of this project is to investigate how Wnt signalling regulates the development and progression of cSCC, with an overall objective to understanding how Wnt-modulating therapeutics could be used to treat the condition in the future. Working in the world-leading Cancer Research UK-skin tumour laboratory housed in the Medical Research Institute (MRI) at the University of Dundee, you will use pre-clinical in vitro and in vivo models to study how Wnt signalling regulates cSCC. In addition, you will have access to patient-derived material to investigate the clinical relevance of your findings. 

Applicants should have (or expect to obtain) a first class or upper first class honours degree (or equivalent) in a biological- or medical-related discipline. The MRI is located at the Ninewells Hospital and Medical School in Dundee and is fully equipped with first-rate facilities for medical research, including state-of-the-art bioimaging, transgenic mouse, and viral transduction facilities. Aside from the research-specific training available within the department, you will also be supported by a wide range of tutor-led workshops focusing on generic research skills and career management training to maximise your personal development as a researcher throughout your PhD programme.  We welcome applications all year-round from home/EU/overseas self-funded applicants who can secure funding to cover all costs associated with PhD study (living costs, tuition fess and bench fees). For application queries please contact Dr Victoria Sherwood (v.sherwood@dundee.ac.uk).

References

1. Jenei, V.*, Sherwood, V.* et al., A t-butyloxycarbonyl-modified Wnt5a-derived hexapeptide functions as a potent antagonist of Wnt5a-dependent melanoma cell invasion. Proceedings of the National     Academy of Sciences of the United States of America, 2009. 106(46): p. 19473-8. (*Equal contribution).

2. Ekstrom, E.J., V. Sherwood, and T. Andersson, Methylation and loss of Secreted Frizzled-Related Protein 3 enhances melanoma cell migration and invasion. PloS one, 2011. 6(4): p. e18674.

3. Sherwood, V., et al., WNT5A-mediated beta-catenin-independent signalling is a novel regulator of cancer cell metabolism. Carcinogenesis, 2014. 35(4): p. 784-94.

4. Sherwood, V., WNT signaling: An emerging mediator of cancer cell metabolism? Mol Cell Biol, 2014.

Supervisor: 
Dr Vicky Sherwood
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