• 24499 Citations
  • 74 h-Index
1977 …2018
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Personal profile

Research

John Hayes received his undergraduate training (1972-1976) in the School of Biological Sciences at the University of Edinburgh, with final year of studies in Molecular Biology. He gained a PhD from the Medical School of the same university in 1980, awarded for investigation into bile acid-binding by glutathione S-transferase (GST) enzymes, which was undertaken in the laboratory of Professor Iain Percy-Robb. Upon completion of his PhD experimental work, he worked for 14 months as a NHS basic-grade Biochemist in the Department of Clinical Chemistry at the Western General Hospital in Edinburgh.

In 1981, Dr Hayes was appointed a Lecturer within the Department of Clinical Chemistry at the University of Edinburgh. Here, he focused research efforts on the biochemistry of the GST superfamily of drug-metabolising enzymes and the induction of certain members by chemoprotective drugs; this led to identification of previously unrecognised inducible GST isoenzymes several of which inactivated the fungal toxin aflatoxin B1. They subsequently demonstrated that upon treatment with chemoprotective agents, induction of these GST could suppress hepatocellular carcinoma caused by exposure to the mycotoxin. In 1991, he took sabbatical leave from the University of Edinburgh to work in the laboratory of Dr Cecil Pickett, Merck Frosst, Montreal, Canada, which was responsible for discovering the antioxidant response element (ARE) in the promoters of genes that can be induced by chemoprotective agents.

In October 1992, Dr Hayes moved as a Reader to the University of Dundee where he undertook research into regulation of drug-metabolising enzymes and identified the aldo-keto reductase 7A family (i.e. AKR7A) of genes, the founding member of which they discovered because it can be induced by chemoprotective drugs and catalyses inactivation of aflatoxin B1. In January 1997, the University of Dundee promoted him to a personal chair. Since then, his interest in the mechanisms by which gene expression is induced by cancer chemoprotective agents via ARE sequences has continued. This line of investigation led to the discovery that the NRF2 transcription factor (i.e. NF-E2 p45-related factor 2) regulates both basal and inducible expression of genes encoding GST, AKR, quinone reductase, glutathione biosynthetic enzymes and components of the thioredoxin antioxidant system, which collectively provide protection against oxidative stressors. Furthermore, his lab was the first to demonstrate that induction of genes regulated via ARE sequences requires stabilisation of NRF2 protein, which is inherently very unstable, through antagonism of the E3 cullin-3 RING ligase substrate adaptor KEAP1 (i.e. Kelch-like ECH-associated protein 1). Collectively, these findings, along with those of other research groups, have led to the recognition that the NRF2-KEAP1 pathway represents the master regulator of cellular antioxidant defences, and is therefore potentially involved in many degenerative diseases in which oxidative stress is implicated in their aetiology or progression. Interestingly, the Hayes laboratory subsequently discovered the existence of three independent stress sensors within KEAP1 that appear to have evolved separately: two of these are triggered by chemoprotective agents, whereas the third is triggered by hydrogen peroxide and various metal ions including Zn2+and Cd2+. Besides KEAP1, the Hayes lab also discovered a separate pathway that regulates NRF2 via ubiquitylation, which involves beta-TrCP (i.e. beta-transducin repeat-containing protein), and is dependent on prior phosphorylation of NRF2 by glycogen synthase kinase-3 GSK-3); this discovery is significant because through GSK-3, it provides a link between NRF2, redox homeostasis and intermediary metabolism.

Ongoing research in the Hayes laboratory has revealed that activation of NRF2 robustly stimulates endogenous antioxidant systems and, in the context of diabetes, non-alcoholic steatohepatitis and cirrhosis, suppresses inflammatory disease and liver fibrosis and blunts gluconeogenesis and lipid biosynthesis whilst promoting catabolism of fatty acids.

Prof Hayes has been a scientific advisor to the Medical Research Council and the Association for International Cancer Research. He has been a scientific advisor and served on the editorial boards of international scientific journals, including the Biochemical Journal, Carcinogenesis, Molecular & Cellular Biology, and the Journal of Pharmacology & Experimental Therapeutics.

The Hayes lab has published a total of 202 peer-reviewed original scientific papers and 28 solicited reviews/commentaries, most of which can be viewed through ResearchGate (www.researchgate.net/profile/John_Hayes9/).

Prof Hayes was elected a Fellow of the Royal Society of Edinburgh in May 2008, and a Fellow of the Society of Biology in September 2008.

Teaching

Prof Hayes contributes to the medical curriculum by providing a SSC module entitled “Antioxidants and Degenerative disease” for first-year MB ChB students in which evidence that dietary supplements improve redox signalling/oxidative stress and mitigate chronic diseases is evaluated. He also provides 10-week SSC research projects for third-year MB ChB students.

Hayes contributes to the BMSc course run for medical undergraduate students on diabetes by providing lectures/tutorials on “Hepatocyte redox status” and “Endoplasmic reticulum stress in non-alcoholic steatohepatitis”.

Hayes contributes to the science curriculum by running journal clubs and providing research projects for final-year undergraduate BSc students doing the Biological & Biomedical Science, the Cancer Biology, and the Cancer Pharmacology streams.

Hayes contributes to the MRes Cancer Biology course by providing research projects.

Keywords

  • R Medicine (General)
  • cancer research
  • drug metabolism
  • oxidative stress
  • non-alcoholic steatohepatitis
  • Nrf2
  • Keap1

Fingerprint Fingerprint is based on mining the text of the person's scientific documents to create an index of weighted terms, which defines the key subjects of each individual researcher.

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Research Output 1977 2018

3 Citations

A partnership with the proteasome: the destructive nature of GSK3

Robertson, H., Hayes, J. D. & Sutherland, C., Jan 2018, In : Biochemical Pharmacology. 147, p. 77-92 16 p.

Research output: Contribution to journalArticle

Open Access
File
Glycogen Synthase Kinase 3
Proteasome Endopeptidase Complex
beta-Transducin Repeat-Containing Proteins
Phosphorylation
Proteins
9 Citations
Open Access
File
NF-E2-Related Factor 2
Fructose
Liver Cirrhosis
Fats
Endoplasmic Reticulum Stress
Cullin Proteins
NF-E2-Related Factor 2
Zinc
Transcription Factors
Switches
1 Citations

Characterization of liver injury, oval cell proliferation and cholangiocarcinogenesis in glutathione S-transferase A3 knockout mice

Crawford, D. R., Ilic, Z., Guest, I., Milne, G. L., Hayes, J. D. & Sell, S., Jul 2017, In : Carcinogenesis. 38, 7, p. 717-727 11 p.

Research output: Contribution to journalArticle

Open Access
File
Aflatoxin B1
Glutathione Transferase
Knockout Mice
Cell Proliferation
Liver

Corrigendum to "Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer"

MacLeod, A. K., Acosta-Jimenez, L., Coates, P. J., McMahon, M., Carey, F. A., Honda, T., Hayes, J. D., Henderson, C. J. & Wolf, C. R., 22 Aug 2017, In : British Journal of Cancer. 117, 1 p., e1

Research output: Contribution to journalArticle

Thesis

Investigating the role of transcription factor Nrf2 in the pathogenesis of NAFLD

Author: Wood, K. L., 2017

Supervisor: Dillon, J. (Supervisor) & Hayes, J. (Supervisor)

Student thesis: Master's ThesisMaster of Science

Investigating the role of transcription factors Nrf2 and Pparα in hepatic lipid metabolism during fasting

Author: Tebay, L., 2015

Supervisor: Hayes, J. (Supervisor) & Dinkova-Kostova, A. (Supervisor)

Student thesis: Doctoral ThesisDoctor of Philosophy

Mechanisms by which natural polyphenols regulate the expression of cytoprotective genes

Author: Xiao, H., 2010

Supervisor: Hayes, J. (Supervisor) & Stewart, D. (External person) (Supervisor)

Student thesis: Doctoral ThesisDoctor of Philosophy

File

Regulation of transcription factors NRF2 and HSF1 in mediating cellular stress responses

Author: Dayalan Naidu, S., 2016

Supervisor: Dinkova-Kostova, A. (Supervisor) & Hayes, J. (Supervisor)

Student thesis: Doctoral ThesisDoctor of Philosophy

File