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  The role of isothiocyanates-derived from natural sources in uveal melanoma chemoprevention (ref: SF18/APP/McDermott)


   Faculty of Health and Life Sciences

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  Prof A McDermott, Prof M Panagiotidis, Dr G Koutsidis  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Uveal melanoma is the most frequent primary intraocular tumor, in Caucasian adults, and one that is very difficult to treat once it becomes metastatic. In fact, there is currently no effective treatment for metastatic uveal melanoma despite the significant progress in the area of cancer therapeutics. Isothiocyanates are phytochemicals derived from cruciferous vegetables and are responsible for exerting a plethora of anticancer (and other biological) effects, thus promoting their utilization in disease prevention and nutritional intervention.
The proposed project will build on current collaboration of the supervisory team with The Watercress Company, UK (provider of 60% of the UK watercress market) and the Northumbria University NUOMICs Centre in order to investigate the role of isothiocyanates in uveal melanoma chemoprevention. Processes for bench-scale characterization and extraction of isothiocyanates derived from natural watercress samples will be developed. The ability of several isothiocyanates (i.e. sulphoraphane, benzyl, phenethyl, allyl and iberin) to induce a chemopreventive role will be demonstrated by utilizing an in vitro experimental model using human uveal melanoma cell lines. Moreover, genomic, proteomic and epigenetic methodologies will be employed in order to identify and characterize key genes, and associated proteins, which become deregulated during the process of the disease development. Such knowledge will not only (i) delineate underlying mechanisms(s) involved in uveal melanoma, and how isothiocyanates may be involved, but also (ii) lead to development of biomarkers descriptive of the disease pathophysiology which could open up the way for “designing” more efficient therapeutic and/or nutritional intervention strategies.
Overall, the proposed project adopts a multidisciplinary approach by bringing together expertise from food, nutritional and biomedical sciences to address an unmet clinically significant need regarding treatment of uveal melanoma, a vision and life threatening cancer.

Eligibility and How to Apply:
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required.

For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/

Please note: Applications should include a covering letter that includes a short summary (500 words max.) of a relevant piece of research that you have previously completed. Applications that do not include the advert reference (e.g. SF18/…) will not be considered.

Deadline for applications: 1st July 2019 for October 2019 start, or 1st December 2018 for March 2019 start
Start Date: October or March

Northumbria University takes pride in, and values, the quality and diversity of our staff. We welcome applications from all members of the community. The University holds an Athena SWAN Bronze award in recognition of our commitment to improving employment practices for the advancement of gender equality and is a member of the Euraxess network, which delivers information and support to professional researchers

Funding Notes

This studentship is only open to self-funding candidates. Self-funding candidates are expected to pay University fees and to provide their own living costs. University fee bands are shown at
https://www.northumbria.ac.uk/study-at-northumbria/fees-funding/pg-fees-funding/postgraduate-research-fees/
This project will incur fees at Band 4.

References

1- Manarang JC, Otteson DC, McDermott AM. Expression of Antimicrobial Peptides by Uveal and Cutaneous Melanoma Cells and Investigation of Their Role in Tumor Cell Migration and Vasculogenic Mimicry. Curr Eye Res. 2017 Nov;42(11):1474-1481
2- Mantso T, Sfakianos A, Atkinson A, Anestopoulos I, Mitsiogianni M, Botaitis S, Perente S, Simopoulos C, Vasileiadis S, Franco R, Pappa A, Panayiotidis MI. Development of a novel experimental in vitro model of isothiocyanate-induced apoptosis in human malignant melanoma cells. Anticancer Res. 2016 Dec;36(12):6303-6309
3. Mitsiogianni M, Amery T, Franco R, Zoumpourlis V, Pappa A, Panayiotisis MI. From chemo-prevention to epigenetic regulation: the role of isothiocyanates in skin cancer prevention. Pharmacol Ther 2018 ePub ahead of print.

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