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New therapeutic targets in inflammation and cancer (O’CONNELLU16SF)

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  • Full or part time
    Dr O'Connell
  • Application Deadline
    No more applications being accepted
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Nrf2 is a transcription factor that regulates the expression of a major cellular defence system, consisting of about 250 cellular anti-oxidants and other cytoprotective proteins (1). In inflammation, Nrf2 activation is beneficial, dampening the production of pro-inflammatory mediators and resolving inflammation (2,3). In cancer, Nrf2 plays a dual role, preventing the onset of cancer by repairing damage but once a tumour has developed, Nrf2 protects it from anti-tumour agents. Due to these important roles in inflammation and cancer, the Nrf2 pathway is currently a major therapeutic target for pharmaceutical companies (1). We have developed small molecules and identified natural products that activate or inhibit Nrf2 (4).
In this project, we will:
a) Explore components of the Nrf2 pathway in immune and cancer cells to identify suitable therapeutic targets
b) Investigate the mechanism by which Nrf2 inhibits inflammation
c) Examine the effects of small molecule libraries on Nrf2 activation and function to identify new leads for therapy.

Funding Notes

This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at http://bit.ly/1Jf7KCr.

A bench fee is also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. The amount charged annually will vary considerably depending on the nature of the project and applicants should contact the primary supervisor for further information about the fee associated with the project.

References

1) O’Connell MA, Hayes JD (2015). The Keap1/Nrf2 pathway in health and disease: from the bench to the clinic. Biochem Soc Trans (in press).
2) Kim J, Cha YN, Surh YJ (2010). A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders. Mutat Res 690, 12-23.
3) Rushworth SA, MacEwan DJ, O’Connell MA (2008). Lipopolysaccharide-induced expression of NAD(P)H:quinone oxidoreductase 1 and heme oxygenase-1 protects against excessive inflammatory responses in human monocytes. J Immunol 181, 6730-6737.
4) Steel R, Cowan J, Payerne E, O'Connell MA, Searcey M (2012). Anti-inflammatory effect of a cell penetrating peptide targeting the Nrf2/Keap1 interaction. ACS Med Chem Letts 3, 407-410.

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