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Targeting steroid metabolism to block colorectal cancer proliferation


Project Description

Our group is a world leader in targeting specific aspects of steroid metabolism to block cancer growth. Our research has been instrumental in the successful pre-clinical and clinical development of various novel anti-cancer compounds. Currently, we are investigating the importance of steroid metabolism in colorectal cancer, with a particular interest in oestrogenic effects on the development and proliferation of this malignancy.

This PhD would aim to examine how key oestrogenic enzymes (17beta hydroxysteroid dehydrogenases (HSD17Bs)) impact steroid metabolism in colorectal cancer, and whether inhibiting these enzymes is a valid therapy for disease. Further experiments would include investigating how steroids effect HSD17Bs expression and activity in colorectal cancer and colon adenomas. Technical skills gained would include comprehensive cell culturing, flow cytometry, ELISA, LC-MS/MS, quantitative PCR, and immunoblotting. Cellular knockdown of HSD17Bs would also be performed through either siRNA or CRISPR, and the consequences of this on proliferation and oestrogen metabolism will be determined.

The overall aim of this PhD project is to identify novel targets for the treatment of colorectal cancer or colon adenoma development and proliferation. These studies will build on previous data generated by the group which have shown how oestrogens can increase colorectal cancer proliferation through activating the G-protein coupled oestrogen receptor (GPER). Thus, inhibiting pre-receptor oestrogen synthesis is a valid option in identifying new treatments for colorectal cancer.

Person Specification
Applicants should have a strong background in cell biology, and preferably with experience of cancer cell culture and analysis of gene expression. They should have a commitment to endocrinology, oncology, or metabolism research and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in Biosciences, Medical Sciences or Cancer Biology.

Informal enquiries should be directed to Dr Paul Foster, email

To be considered for this studentship, please send the following documents to Viktorija Ziabliceva, email :
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.





Funding Notes

Self-funded applications only.

References

• Gilligan LC, Rahman HP, Hewitt AM, Sitch AJ, Gondal A, Arvaniti A, Taylor AE, Read ML, Morton DG, Foster PA. Estrogen Activation by Steroid Sulfatase Increases Colorectal Cancer Proliferation via GPER. J Clin Endocrinol Metab. 2017 Dec 1;102(12):4435-4447
• Gilligan LC, Gondal A, Tang V, Hussain MT, Arvaniti A, Hewitt AM, Foster PA. Estrone Sulfate Transport and Steroid Sulfatase Activity in Colorectal Cancer: Implications for Hormone Replacement Therapy. Front Pharmacol. 2017 Mar 7;8:103.
• Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA. The Regulation of Steroid Action by Sulfation and Desulfation. Endocr Rev. 2015 Oct;36(5):526-63.
• Foster PA. Oestrogen and colorectal cancer: mechanisms and controversies. Int J Colorectal Dis. 2013 Jun;28(6):737-49.

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