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Role of Desmoglein-3 in regulating the YAP-Hippo pathway in cancer

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Project Description:

Applications are invited for a 4-year PhD within a multidisciplinary and integrative research team in The Centre of Immunobiology and Regenerative Medicine, Institute of Dentistry.

Background:

Desmoglein-3 (Dsg3) is a member of the desmosomal cadherins that mediate epithelial cell-cell adhesion in desmosomes (DSMs). The expression of Dsg3 is predominantly located in the basal layer of epidermis in skin but is uniform across the entire stratified epithelium in oral mucosa. Dsg3 is characterized to be associated with two diseases, i.e. cancer and pemphigus. In the former, Dsg3 is upregulated and in the latter, its expression is reduced due to enhanced protein degradation mediated by autoantibody binding.

Perhaps, Dsg3 is best known as Pemphigus Vulgaris Antigen (PVA). Pemphigus Vulgaris is a life-threatening autoimmune blistering disease in which Dsg3 is targeted by circulating autoantibodies, leading to disruption of cell-cell adhesion and blister formation in the skin and mucous membranes. Increasing evidence suggests that the action of Dsg3 is not restricted to DSM adhesion and it also plays a role in cell signal transduction. Various signaling pathways, such as Src, Ezrin and Rho GTPases Rac1/cdc42 and transcription factor c-Jun/AP-1 that are known to be activated in cancer, are found to be regulated by Dsg3 (Tsang et al., PloS One 2010, Exp Cell Res and J Pathol 2012, Brown et al., Oncogene 2014).

Aims:

Recently, we have shown that Dsg3 also plays a role in regulating the YAP-Hippo signaling pathway that is known to control organ growth and tissue homeostasis and its deregulation contributes to cancer development. Thus, the aim of this project is to investigate this pathway in cancer cell lines derived from cutaneous and oral squamous cell carcinoma and to explore whether its inhibition has any impact on cell behaviours, such as cell proliferation and migration/invasion.

The findings from this study will have important implications in the advancement our knowledge of this pathway in tumour cell biology and may uncover potential pharmacological targets that could be exploited for cancer therapy.

Person specification:

• Ideally, prospective students should have a degree in cell and molecular biology (minimum degree of a 2:1)

How to apply:

For more information regarding the project, please contact Dr H. Wan ().

Applications should be submitted through the Queen Mary application system. Please indicate the project title and supervisor in the ‘Research Degree Programmes - Additional Questions’ section of the application.

Alongside the application form, please send the following supporting documents:
• Curriculum Vitae (CV)
• Copies of your degree certificates with transcripts
• Proof of English language ability for overseas applicants from non-English speaking countries
• A one-side A4 statement of purpose. This should set out your previous academic or other experience relevant to the proposed research; why you wish to undertake this research at QMUL; your previous research or professional training and what further training you think you will need to complete a PhD; and what ethical issues you will need to consider in undertaking this research.
• Two references. At least one reference must be from an academic referee who is in a position to comment on the standard of your academic work and suitability for postgraduate level study. Where appropriate, a second referee can provide comment on your professional experience.

Please contact Charlotte Royle () with any queries about the application process.

Funding Notes

We will consider applications from prospective students with a source of funding to cover tuition fees and bench fees for three years full-time or 6 years part-time. Both self-funded and sponsored students will be considered.

UK and EU nationality self-funded students might be eligible for both the cost of tuition fees and a yearly stipend over the course of the PhD programme from the Student Finance England: View Website

References

1. S. M. Tsang, et al., "Desmoglein 3, via an interaction with E-cadherin, is associated with activation of Src," PLoS. One. 5(12), e14211 (2010).
2. S. M. Tsang, et al., "Desmoglein 3 acting as an upstream regulator of Rho GTPases, Rac-1/Cdc42 in the regulation of actin organisation and dynamics," Exp. Cell Res. 318(18), 2269 (2012).
3. S. M. Tsang, et al., "Non-junctional human desmoglein 3 acts as an upstream regulator of Src in E-cadherin adhesion, a pathway possibly involved in the pathogenesis of pemphigus vulgaris," J Pathol. 227(1), 81 (2012).
4. L. Brown, et al., "Desmoglein 3 promotes cancer cell migration and invasion by regulating activator protein 1 and protein kinase C-dependent-Ezrin activation," Oncogene 33(18), 2363 (2014).
5. L. Brown and H. Wan, "Desmoglein 3: a help or a hindrance in cancer progression?," Cancers. (Basel) 7(1), 266 (2015).

How good is research at Queen Mary University of London in Allied Health Professions, Dentistry, Nursing and Pharmacy?

FTE Category A staff submitted: 32.20

Research output data provided by the Research Excellence Framework (REF)

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