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Free Radicals Abroad - University of Dundee, Scotland

1 (HSF1), the master regulator of the heat shock response, using

biochemical and biophysical approaches as well as mammalian cell

culture and mouse models of human disease.

To gain mechanistic understanding of the regulation of NRF2 and HSF1,

we work with the groups of John Hayes, Calum Sutherland, Steve

Keyse, and Michael Ashford. With funding from Cancer Research

UK, we have developed a mouse model of cutaneous squamous cell

carcinogenesis (cSCC) caused by chronic exposure to solar-simulated

UV (SSUV) radiation. Using this model, we found that pharmacologic

or genetic (by KEAP1 knockdown) activation of NRF2 inhibits tumor

development, and that deletion of NRF2 abrogates the protective effect.
Abbena Dinkova-Kostova's lab at the University of Dundee.
Together with our clinical colleagues (Charlotte Proby, Sally Ibbotson,

James Ferguson, and Robert Dawe), we have conducted a double-

blind placebo-controlled clinical trial and shown the protective effect
Dundee is a small city in Scotland situated within the Eastern Central
of pharmacologic NRF2 activation against SSUV-induced erythema, a
Lowlands on the North bank of the river Tay, which lows into the
surrogate for skin cancer risk, in healthy human subjects.
North Sea only a couple of miles away. Dundee is also known as “One

City, Many Discoveries”. Historically, the irst of these discoveries In collaboration with Philip A. Cole (Johns Hopkins University) and

was the RRS “Discovery”, the ship of Robert Falcon Scott's Antarctic Young-Hoon Ahn (Wayne State University), we found that many NRF2

expedition, which was built in Dundee and is now a museum at the activators also activate HSF1, in part by modifying cysteine residues of

city harbor. Captain Scott’s “Discovery” continues to be followed by heat shock protein 90 (HSP90) and inhibiting its function as a negative

many more discoveries, mainly in the areas of biomedical sciences
regulator of HSF1. In the area of drug discovery, we collaborate with

and technological industries. In 2014, Dundee was named by the United Tadashi Honda (Stony Brook University), a medicinal chemist who

Nations as the UK's irst UNESCO City of Design. In the same year, the designs and synthesized new NRF2 activators, and with Ian Copple (the

University of Dundee was ranked top University for Biological Sciences MRC Human Toxicology Unit, University of Liverpool) who evaluates the

and for impact in Clinical Medicine in the UK.
in vitro therapeutic index of the new compounds.

Our laboratory is at the School of Medicine of the University of Dundee, We teach life sciences and medical students, and train local and

where our group works in close collaboration with the groups of basic European (ERASMUS) graduate students. We are most proud of the

scientists as well as clinical academics. The overarching goal of our achievement of our students who have received academic awards

research is to understand the cellular stress responses to oxidative, both locally and nationally, such as the Best Poster Prize (to Macha

electrophilic and inlammatory stress, and to use this knowledge for
Aldighieri), the Best Student Presentation (to Sharadha Dayalan Naidu

developing strategies for disease prevention and treatment. We are and Kevin Roth) at the Medical School Graduate Research Symposium,

working towards understanding the regulation of transcription factors the Biochemical Society Centenary Poster Prize (to Liam Baird) and

nuclear factor-erythroid 2 p45-related factor 2 (NRF2), the master the Sir James Black Award for Outstanding Achievements (to Egle

regulator of the cellular redox homeostasis, and heat shock factor
Gaurilcikaite). 

SfRBM Newsletter // September 2016 // Free Radicals Abroad

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