John Hayes

+44 (0)1382 383182
Professor of Molecular Carcinogenesis

Bio

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.

Publications

Mc Mahon, M, Swift, SR & Hayes, JD 2018,

'Zinc-binding triggers a conformational-switch in the cullin-3 substrate adaptor protein KEAP1 that controls transcription factor NRF2' Toxicology and Applied Pharmacology, vol. 360, pp. 45-47.
https://doi.org/10.1016/j.taap.2018.09.033

Research output: Contribution To Journal



Sharma, RS, Harrison, DJ, Kisielewski, D, Cassidy, DM, Mc Neilly, AD, Gallagher, JR, Walsh, SV, Honda, T, Mc Crimmon, RJ, Dinkova-Kostova, AT, Ashford, MLJ, Dillon, JF & Hayes, JD 2018,

'Experimental Nonalcoholic Steatohepatitis and Liver Fibrosis Are Ameliorated by Pharmacologic Activation of Nrf2 (NF-E2 p45-Related Factor 2)' CMGH: Cellular and Molecular Gastroenterology and Hepatology, vol. 5, no. 3, pp. 367-398.
https://doi.org/10.1016/j.jcmgh.2017.11.016

Research output: Contribution To Journal



Robertson, H, Hayes, JD & Sutherland, C 2018,

'A partnership with the proteasome: the destructive nature of GSK3' Biochemical Pharmacology, vol. 147, pp. 77-92.
https://doi.org/10.1016/j.bcp.2017.10.016

Research output: Contribution To Journal



Torrente, L, Sanchez, C, Moreno Dorta, R, Chowdhry, S, Cabello, P, Isono, K, Koseki, H, Honda, T, Hayes, J, Dinkova-Kostova, A & de la Vega, L 2017,

'Crosstalk between NRF2 and HIPK2 shapes cytoprotective responses' Oncogene, vol. 36, no. 44, pp. 6204-6212.
https://doi.org/10.1038/onc.2017.221

Research output: Contribution To Journal



Hayes, JD & Dinkova-Kostova, AT 2017,

'Oncogene-Stimulated Congestion at the KEAP1 Stress Signaling Hub Allows Bypass of NRF2 and Induction of NRF2-Target Genes that Promote Tumor Survival' Cancer Cell, vol. 32, no. 5, pp. 539-541.
https://doi.org/10.1016/j.ccell.2017.10.009

Research output: Contribution To Journal



Hayes, JD & Dinkova-Kostova, AT 2017,

'Epigenetic Control of NRF2-Directed Cellular Antioxidant Status in Dictating Life-Death Decisions' Molecular Cell, vol. 68, no. 1, pp. 5-7.
https://doi.org/10.1016/j.molcel.2017.09.023

Research output: Contribution To Journal



Mac Leod, AK, Acosta-Jimenez, L, Coates, PJ, Mc Mahon, M, Carey, FA, Honda, T, Hayes, JD, Henderson, CJ & Wolf, CR 2017,

'Corrigendum to "Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer"' British Journal of Cancer, vol. 117, e1.
https://doi.org/10.1038/bjc.2017.80

Research output: Contribution To Journal



Crawford, DR, Ilic, Z, Guest, I, Milne, GL, Hayes, JD & Sell, S 2017,

'Characterization of liver injury, oval cell proliferation and cholangiocarcinogenesis in glutathione S-transferase A3 knockout mice' Carcinogenesis, vol. 38, no. 7, pp. 717-727.
https://doi.org/10.1093/carcin/bgx048

Research output: Contribution To Journal



Hayes, JD, Ebisine, K, Sharma, RS, Chowdhry, S, Dinkova-Kostova, AT & Sutherland, C 2016,

'Regulation of the CNC-b ZIP transcription factor Nrf2 by Keap1 and the axis between GSK-3 and β-Tr CP' Current Opinion in Toxicology, vol. 1, pp. 92-103.
https://doi.org/10.1016/j.cotox.2016.10.003

Research output: Contribution To Journal



Mc Neilly, AD, Gallagher, JR, Dinkova-Kostova, AT, Hayes, JD, Sharkey, J, Ashford, MLJ & Mc Crimmon, RJ 2016,

'Nrf2-mediated neuroprotection response to recurrent hypoglycemia is insufficient to prevent cognitive impairment in a rodent model of type 1 diabetes' Diabetes, vol. 65, no. 10, pp. 3151-3160.
https://doi.org/10.2337/DB15-1653

Research output: Contribution To Journal



Tebay, LE, Robertson, H, Durant, ST, Vitale, SR, Penning, TM, Dinkova-Kostova, AT & Hayes, JD 2015,

'Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease' Free Radical Biology and Medicine, vol. 88, no. Part B, pp. 108-146.
https://doi.org/10.1016/j.freeradbiomed.2015.06.021

Research output: Contribution To Journal



Zhang, Y, Li, S, Xiang, Y, Qiu, L, Zhao, H & Hayes, JD 2015,

'The selective post-translational processing of transcription factor Nrf1 yields distinct isoforms that dictate its ability to differentially regulate gene expression' Scientific Reports, vol. 5, 12983.
https://doi.org/10.1038/srep12983

Research output: Contribution To Journal



Agathanggelou, A, Weston, VJ, Perry, T, Davies, NJ, Skowronska, A, Payne, DT, Fossey, JS, Oldreive, CE, Wei, W, Pratt, G, Parry, H, Oscier, D, Coles, SJ, Hole, PS, Darley, RL, Mc Mahon, M, Hayes, JD, Moss, P, Stewart, G, Taylor, AMR & Stankovic, T 2015,

'Targeting the Ataxia Telangiectasia Mutated-null phenotype in chronic lymphocytic leukemia with pro-oxidants' Haematologica, vol. 100, no. 8, pp. 1076-1085.
https://doi.org/10.3324/haematol.2014.115170

Research output: Contribution To Journal



Hayes, JD, Chowdhry, S, Dinkova-Kostova, AT & Sutherland, C 2015,

'Dual regulation of transcription factor Nrf2 by Keap1 and by the combined actions of β-Tr CP and GSK-3' Biochemical Society Transactions, vol. 43, no. 4, pp. 611-620.
https://doi.org/10.1042/BST20150011

Research output: Contribution To Journal



O'Connell, MA & Hayes, JD 2015,

'The Keap1/Nrf2 pathway in health and disease: from the bench to the clinic' Biochemical Society Transactions, vol. 43, no. 4, pp. 687-689.
https://doi.org/10.1042/BST20150069

Research output: Contribution To Journal



Bell, KFS, Al-Mubarak, B, Martel, MA, Mc Kay, S, Wheelan, N, Hasel, P, Márkus, NM, Baxter, P, Deighton, RF, Serio, A, Bilican, B, Chowdhry, S, Meakin, PJ, Ashford, MLJ, Wyllie, DJA, Scannevin, RH, Chandran, S, Hayes, JD & Hardingham, GE 2015,

'Neuronal development is promoted by weakened intrinsic antioxidant defences due to epigenetic repression of Nrf2' Nature Communications, vol. 6, 7066.
https://doi.org/10.1038/ncomms8066

Research output: Contribution To Journal



Tsujita, T, Peirce, V, Baird, L, Matsuyama, Y, Takaku, M, Walsh, SV, Griffin, JL, Uruno, A, Yamamoto, M & Hayes, JD 2014,

'Transcription factor Nrf1 negatively regulates the cystine/glutamate transporter and lipid-metabolizing enzymes' Molecular and Cellular Biology, vol. 34, no. 20, pp. 3800-3816.
https://doi.org/10.1128/MCB.00110-14

Research output: Contribution To Journal



Meakin, PJ, Chowdhry, S, Sharma, RS, Ashford, FB, Walsh, SV, Mc Crimmon, RJ, Dinkova-Kostova, AT, Dillon, JF, Hayes, JD & Ashford, MLJ 2014,

'Susceptibility of Nrf2-null mice to steatohepatitis and cirrhosis upon consumption of a high-fat diet is associated with oxidative stress, perturbation of the unfolded protein response, and disturbance in the expression of metabolic enzymes, but not with insulin resistance' Molecular and Cellular Biology, vol. 34, no. 17, pp. 3305-3320.
https://doi.org/10.1128/MCB.00677-14

Research output: Contribution To Journal



Lewerenz, J, Baxter, P, Kassubek, R, Albrecht, P, Van Liefferinge, J, Westhoff, M-A, Halatsch, M-E, Karpel-Massler, G, Meakin, PJ, Hayes, JD, Aronica, E, Smolders, I, Ludolph, AC, Methner, A, Conrad, M, Massie, A, Hardingham, GE & Maher, P 2014,

'Phosphoinositide 3-kinases upregulate system xc- via eukaryotic initiation factor 2α and activating transcription factor 4-A pathway active in glioblastomas and epilepsy' Antioxidants & Redox Signaling, vol. 20, no. 18, pp. 2907-2922.
https://doi.org/10.1089/ars.2013.5455

Research output: Contribution To Journal



Hayes, JD & Dinkova-Kostova, AT 2014,

'The Nrf2 regulatory network provides an interface between redox and intermediary metabolism' Trends in Biochemical Sciences, vol. 39, no. 4, pp. 199-218.
https://doi.org/10.1016/j.tibs.2014.02.002

Research output: Contribution To Journal



Zhang, Y, Ren, Y, Li, S & Hayes, JD 2014,

'Transcription factor Nrf1 Is topologically repartitioned across membranes to enable target gene transactivation through Its acidic glucose-responsive domains' PLo S ONE, vol. 9, no. 4, e93458.
https://doi.org/10.1371/journal.pone.0093458

Research output: Contribution To Journal



Nagle, AA, Reddy, SA, Bertrand, H, Tajima, H, Dang, T-M, Wong, S-C, Hayes, JD, Wells, G & Chew, E-H 2014,

'3-(2-oxoethylidene)indolin-2-one derivatives activate Nrf2 and inhibit NF-κB: potential candidates for chemoprevention' Chem Med Chem, vol. 9, no. 8, pp. 1763-1774.
https://doi.org/10.1002/cmdc.201402038

Research output: Contribution To Journal



Deighton, RF, Márkus, NM, Al-Mubarak, B, Bell, KFS, Papadia, S, Meakin, PJ, Chowdhry, S, Hayes, J & Hardingham, GE 2014,

'Nrf2 target genes can be controlled by neuronal activity in the absence of Nrf2 in astrocytes' Proceedings of the National Academy of Sciences USA, vol. 111, no. 18, 24753562, pp. E1818-1820.
https://doi.org/10.1073/pnas.1402097111

Research output: Contribution To Journal



Gan, F-F, Leng, H, Ang, X, Reddy, SA, Lee, SS-H, Yang, H, Tan, S-H, Hayes, JD, Chui, W-K & Chew, E-H 2013,

'A novel shogaol analog suppresses cancer cell invasion and inflammation, and displays cytoprotective effects through modulation of NF-κB and Nrf2-Keap1 signaling pathways' Toxicology and Applied Pharmacology, vol. 272, no. 3, pp. 852-862.
https://doi.org/10.1016/j.taap.2013.07.011

Research output: Contribution To Journal



Hourihan, JM, Kenna, JG & Hayes, JD 2013,

'The Gasotransmitter Hydrogen Sulfide Induces Nrf2-Target Genes by Inactivating the Keap1 Ubiquitin Ligase Substrate Adaptor Through Formation of a Disulfide Bond Between Cys-226 and Cys-613.' Antioxidants & Redox Signaling, vol. 19, no. 5, pp. 465-481.
https://doi.org/10.1089/ars.2012.4944

Research output: Contribution To Journal



Zhang, Y & Hayes, JD 2013,

'The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity' Scientific Reports, vol. 3, 2006.
https://doi.org/10.1038/srep02006

Research output: Contribution To Journal



Wang, H, Liu, K, Geng, M, Gao, P, Wu, X, Hai, Y, Li, Y, Li, Y, Luo, L, Hayes, JD, Wang, XJ & Tang, X 2013,

'RXRα Inhibits the NRF2-ARE Signaling Pathway through a Direct Interaction with the Neh7 Domain of NRF2' Cancer Research, vol. 73, no. 10, pp. 3097-3108.
https://doi.org/10.1158/0008-5472.CAN-12-3386

Research output: Contribution To Journal



Gupta, K, Patani, R, Baxter, P, Serio, A, Story, D, Tsujita, T, Hayes, JD, Pedersen, RA, Hardingham, GE & Chandran, S 2012,

'Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms' Cell Death & Differentiation, vol. 19, no. 5, pp. 779-787.
https://doi.org/10.1038/cdd.2011.154

Research output: Contribution To Journal



Hancock, R, Bertrand, HC, Tsujita, T, Naz, S, El-Bakry, A, Laoruchupong, J, Hayes, JD & Wells, G 2012,

'Peptide inhibitors of the Keap1-Nrf2 protein-protein interaction' Free Radical Biology and Medicine, vol. 52, no. 2, pp. 444-451.
https://doi.org/10.1016/j.freeradbiomed.2011.10.486

Research output: Contribution To Journal



Hayes, JD & Ashford, MLJ 2012,

'Nrf2 orchestrates fuel partitioning for cell proliferation' Cell Metabolism, vol. 16, no. 2, pp. 139-141.
https://doi.org/10.1016/j.cmet.2012.07.009

Research output: Contribution To Journal



Chowdhry, S, Zhang, Y, Mc Mahon, M, Sutherland, C, Cuadrado, A & Hayes, JD 2012,

'Nrf2 is controlled by two distinct β-Tr CP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity' Oncogene, vol. 32, pp. 3765-3781.
https://doi.org/10.1038/onc.2012.388

Research output: Contribution To Journal



Rada, P, Rojo, AI, Evrard-Todeschi, N, Innamorato, NG, Cotte, A, Jaworski, T, Tobón-Velasco, JC, Devijver, H, García-Mayoral, MF, Van Leuven, F, Hayes, JD, Bertho, G & Cuadrado, A 2012,

'Structural and functional characterization of Nrf2 degradation by the glycogen synthase kinase 3/β-Tr CP Axis' Molecular and Cellular Biology, vol. 32, no. 17, pp. 3486-99.
https://doi.org/10.1128/MCB.00180-12

Research output: Contribution To Journal



Abdullah, A, Kitteringham, NR, Jenkins, RE, Goldring, C, Higgins, L, Yamamoto, M, Hayes, J & Park, BK 2012,

'Analysis of the role of Nrf2 in the expression of liver proteins in mice using two-dimensional gel-based proteomics' Pharmacological Reports, vol. 64, no. 3, pp. 680-697.

Research output: Contribution To Journal



Xiao, H, Hourihan, JM, Brown, L, Mc Mahon, M, Stewart, D & Hayes, JD 2011,

'Nrf2-mediated induction of antioxidant response element-driven gene expression by flavonoids is dependent on their chemical structure' Toxicology, vol. 290, no. 2-3, pp. 126-127.
https://doi.org/10.1016/j.tox.2011.09.046

Research output: Contribution To Journal



Higgins, LG & Hayes, JD 2011,

'The cap'n'collar transcription factor Nrf2 mediates both intrinsic resistance to environmental stressors and an adaptive response elicited by chemopreventive agents that determines susceptibility to electrophilic xenobiotics' Chemico-Biological Interactions, vol. 192, no. 1-2, pp. 37-45.
https://doi.org/10.1016/j.cbi.2010.09.025

Research output: Contribution To Journal



Higgins, LG & Hayes, JD 2011,

'Mechanisms of induction of cytosolic and microsomal glutathione transferase (GST) genes by xenobiotics and pro-inflammatory agents' Drug Metabolism Reviews, vol. 43, no. 2, pp. 92-137.
https://doi.org/10.3109/03602532.2011.567391

Research output: Contribution To Journal



Rada, P, Rojo, AI, Chowdhry, S, Mc Mahon, M, Hayes, JD & Cuadrado, A 2011,

'SCF/{beta}-Tr CP promotes glycogen synthase kinase 3-dependent degradation of the Nrf2 transcription factor in a Keap1-independent manner' Molecular and Cellular Biology, vol. 31, no. 6, pp. 1121-1133.
https://doi.org/10.1128/MCB.01204-10

Research output: Contribution To Journal



Bell, KF, Al-Mubarak, B, Fowler, JH, Baxter, PS, Gupta, K, Tsujita, T, Chowdhry, S, Patani, R, Chandran, S, Horsburgh, K, Hayes, JD & Hardingham, GE 2011,

'Mild oxidative stress activates Nrf2 in astrocytes, which contributes to neuroprotective ischemic preconditioning' Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 1, pp. E1-E2.
https://doi.org/10.1073/pnas.1015229108

Research output: Contribution To Journal



Mc Mahon, M, Lamont, DJ, Beattie, KA & Hayes, JD 2010,

'Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals' Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 44, pp. 18838-18843.
https://doi.org/10.1073/pnas.1007387107

Research output: Contribution To Journal



Lewis, KN, Mele, J, Hayes, JD & Buffenstein, R 2010,

'Nrf2, a Guardian of Healthspan and Gatekeeper of Species Longevity' Integrative and Comparative Biology, vol. 50, no. 5, pp. 829-843.
https://doi.org/10.1093/icb/icq034

Research output: Contribution To Journal



Young, R, Wolf, CR, Brown, K, Hayes, JD & Whitelaw, CBA 2010,

'Spatial monitoring of toxicity in HMOX-Lac Z transgenic mice' Transgenic Research, vol. 19, no. 5, pp. 897-902.
https://doi.org/10.1007/s11248-010-9363-z

Research output: Contribution To Journal



Zhang, Y & Hayes, JD 2010,

'Identification of topological determinants in the N-terminal domain of transcription factor Nrf1 that control its orientation in the endoplasmic reticulum membrane' Biochemical Journal, vol. 430, pp. 497-510.
https://doi.org/10.1042/BJ20100471

Research output: Contribution To Journal



Young, R, Hayes, JD, Brown, K, Wolf, CR & Whitelaw, CBA 2010,

'Peroxiredoxin Gene Expression Signatures in Liver Reflect Toxic Insult' ASSAY and Drug Development Technologies, vol. 8, no. 4, pp. 512-517.
https://doi.org/10.1089/adt.2009.0246

Research output: Contribution To Journal



Jain, A, Lamark, T, Sjottem, E, Larsen, KB, Awuh, JA, Overvatn, A, Mc Mahon, M, Hayes, JD & Johansen, T 2010,

'p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription' Journal of Biological Chemistry, vol. 285, no. 29, pp. 22576-22591.
https://doi.org/10.1074/jbc.M110.118976

Research output: Contribution To Journal



Kitteringham, NR, Abdullah, A, Walsh, J, Randle, L, Jenkins, RE, Sison, R, Goldring, CEP, Powell, H, Sanderson, C, Williams, S, Higgins, L, Yamamoto, M, Hayes, J & Park, BK 2010,

'Proteomic analysis of Nrf2 deficient transgenic mice reveals cellular defence and lipid metabolism as primary Nrf2-dependent pathways in the liver' Journal of Proteomics, vol. 73, no. 8, pp. 1612-1631.
https://doi.org/10.1016/j.jprot.2010.03.018

Research output: Contribution To Journal



Weber, JE, Oakley, AJ, Christ, AN, Clark, AG, Hayes, JD, Hall, R, Hume, DA, Board, PG, Smythe, ML & Flanagan, JU 2010,

'Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D-2 synthase' European Journal of Medicinal Chemistry, vol. 45, no. 2, pp. 447-454.
https://doi.org/10.1016/j.ejmech.2009.10.025

Research output: Contribution To Journal



Mac Leod, AK, Kelly, VP, Higgins, LG, Kelleher, MO, Price, SA, Bigley, AL, Betton, GR & Hayes, JD 2010,

'Expression and Localization of Rat Aldo-Keto Reductases and Induction of the 1B13 and 1D2 Isoforms by Phenolic Antioxidants' Drug Metabolism and Disposition, vol. 38, no. 2, pp. 341-346.
https://doi.org/10.1124/dmd.109.030544

Research output: Contribution To Journal



Wang, XJ, Hayes, JD, Higgins, LG, Wolf, CR & Dinkova-Kostova, AT 2010,

'Activation of the NRF2 Signaling Pathway by Copper-Mediated Redox Cycling of Para- and Ortho-Hydroquinones' Chemistry & Biology, vol. 17, no. 1, pp. 75-85.
https://doi.org/10.1016/j.chembiol.2009.12.013

Research output: Contribution To Journal



Hayes, JD, Mc Mahon, M, Chowdhry, S & Dinkova-Kostova, AT 2010,

'Cancer chemoprevention mechanisms mediated through the Keap1-Nrf2 pathway' Antioxidants & Redox Signaling, vol. 13, no. 11, pp. 1713-1748.
https://doi.org/10.1089/ars.2010.3221

Research output: Contribution To Journal



Chowdhry, S, Nazmy, MH, Meakin, PJ, Dinkova-Kostova, AT, Walsh, SV, Tsujita, T, Dillon, JF, Ashford, MLJ & Hayes, JD 2010,

'Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis' Free Radical Biology and Medicine, vol. 48, no. 2, pp. 357-371.
https://doi.org/10.1016/j.freeradbiomed.2009.11.007

Research output: Contribution To Journal



Hayes, JD, Dinkova-Kostova, AT & Mc Mahon, M 2009,

'Cross-talk between Transcription Factors Ah R and Nrf2: Lessons for Cancer Chemoprevention from Dioxin' Toxicological Sciences, vol. 111, no. 2, pp. 199-201.
https://doi.org/10.1093/toxsci/kfp168

Research output: Contribution To Journal



Kelleher, MO, Mc Mahon, M, Eggleston, IM, Dixon, MJ, Taguchi, K, Yamamoto, M & Hayes, JD 2009,

'1-Cyano-2,3-epithiopropane is a novel plant-derived chemopreventive agent which induces cytoprotective genes that afford resistance against the genotoxic alpha,beta-unsaturated aldehyde acrolein' Carcinogenesis, vol. 30, no. 10, pp. 1754-1762.
https://doi.org/10.1093/carcin/bgp182

Research output: Contribution To Journal



Mac Leod, AK, Mc Mahon, M, Plummer, SM, Higgins, LG, Penning, TM, Igarashi, K & Hayes, JD 2009,

'Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds' Carcinogenesis, vol. 30, no. 9, pp. 1571-1580.
https://doi.org/10.1093/carcin/bgp176

Research output: Contribution To Journal



Higgins, LG, Kelleher, MO, Eggleston, IM, Itoh, K, Yamamoto, M & Hayes, JD 2009,

'Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents' Toxicology and Applied Pharmacology, vol. 237, no. 3, pp. 267-280.
https://doi.org/10.1016/j.taap.2009.03.005

Research output: Contribution To Journal



Randle, LE, Goldring, CEP, Jenkins, RE, Denk, D, Antoine, DJ, Sison, RL, Williams, DP, Hayes, JD, Kitteringham, NR & Park, BK 2009,

'A biochemical, toxicological, and proteomic analysis investigating the effect of Nrf2 gene deletion on paracetamol-induced hepatoxicity In Vivo' Drug Metabolism Reviews, vol. 41, pp. 23-24.
https://doi.org/10.1080/03602530902800624

Research output: Contribution To Journal



Hayes, JD & Mc Mahon, M 2009,

'NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer' Trends in Biochemical Sciences, vol. 34, no. 4, pp. 176-188.
https://doi.org/10.1016/j.tibs.2008.12.008

Research output: Contribution To Journal



Zhang, Y, Lucocq, JM & Hayes, JD 2009,

'The Nrf1 CNC/b ZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors' Biochemical Journal, vol. 418, pp. 293-310.
https://doi.org/10.1042/BJ20081575

Research output: Contribution To Journal



Zhang, Y, Kobayashi, A, Yamamoto, M & Hayes, JD 2009,

'The Nrf3 transcription factor is a membrane-bound glycoprotein targeted to the endoplasmic reticulum through Its N-terminal Homology Box 1 Sequence' Journal of Biological Chemistry, vol. 284, no. 5, pp. 3195-3210.
https://doi.org/10.1074/jbc.M805337200

Research output: Contribution To Journal



Zhang, Y & Hayes, JD 2009,

'Molecular and cellular control of the membrane-bound Nrf1 transcription factor' International Journal of Molecular Medicine, vol. 24, pp. S40-S40.

Research output: Contribution To Journal



Ohtsuji, M, Katsuoka, F, Kobayashi, A, Aburatani, H, Hayes, JD & Yamamoto, M 2008,

'Nrf1 and Nrf2 Play Distinct Roles in Activation of Antioxidant Response Element-dependent Genes' Journal of Biological Chemistry, vol. 283, no. 48, pp. 33554-33562.
https://doi.org/10.1074/jbc.M804597200

Research output: Contribution To Journal



Soriano, FX, Leveille, F, Papadia, S, Higgins, LG, Varley, J, Baxter, P, Hayes, JD & Hardingham, GE 2008,

'Induction of sulfiredoxin expression and reduction of peroxiredoxin hyperoxidation by the neuroprotective Nrf2 activator 3H-1,2-dithiole-3-thione' Journal of Neurochemistry, vol. 107, no. 2, pp. 533-543.
https://doi.org/10.1111/j.1471-4159.2008.05648.x

Research output: Contribution To Journal



Copple, IM, Goldring, CE, Jenkins, RE, Chia, AJL, Randle, LE, Hayes, JD, Kitteringham, NR & Park, BK 2008,

'The hepatotoxic metabolite of acetaminophen directly activates the Keap1-Nrf2 cell defense system' Hepatology, vol. 48, no. 4, pp. 1292-1301.
https://doi.org/10.1002/hep.22472

Research output: Contribution To Journal



Hayes, JD, Kelleher, MO & Eggleston, IM 2008,

'The cancer chemopreventive actions of phytochemicals derived from glucosinolates' European Journal of Nutrition, vol. 47, pp. 73-88.
https://doi.org/10.1007/s00394-008-2009-8

Research output: Contribution To Journal



Higgins, LG, Cavin, C, Toh, K, Yamamoto, M & Hayes, JD 2008,

'Induction of cancer chemopreventive enzymes by coffee is mediated by transcription factor Nrf2. Evidence that the coffee-specific diterpenes cafestol and kahweol confer protection against acrolein' Toxicology and Applied Pharmacology, vol. 226, no. 3, pp. 328-337.
https://doi.org/10.1016/j.taap.2007.09.018

Research output: Contribution To Journal



Wang, XJ, Hayes, JD, Henderson, CJ & Wolf, CR 2007,

'Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha' Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 49, pp. 19589-19594.
https://doi.org/10.1073/pnas.0709483104

Research output: Contribution To Journal



Zhang, Y, Lucocq, JM, Yamamoto, M & Hayes, JD 2007,

'The NHB1 (N-terminal homology box 1) sequence in transcription factor Nrf1 is required to anchor it to the endoplasmic reticulum and also to enable its asparagine-glycosylation' Biochemical Journal, vol. 408, no. 2, pp. 161-172.
https://doi.org/10.1042/BJ20070761

Research output: Contribution To Journal



Cavin, C, Delatour, T, Marin-Kuan, M, Holzhäuser, D, Higgins, L, Bezençon, C, Guignard, G, Junod, S, Richoz-Payot, J, Gremaud, E, Hayes, JD, Nestler, S, Mantle, P & Schilter, B 2007,

'Reduction in antioxidant defenses may contribute to ochratoxin A toxicity and carcinogenicity' Toxicological Sciences, vol. 96, no. 1, pp. 30-9.
https://doi.org/10.1093/toxsci/kfl169

Research output: Contribution To Journal



Zhang, Y, Crouch, DH, Yamamoto, M & Hayes, JD 2006,

'Negative regulation of the Nrf1 transcription factor by its N-terminal domain is independent of Keap1: Nrf1, but not Nrf2, is targeted to the endoplasmic reticulum' Biochemical Journal, vol. 399, no. 3, pp. 373-385.
https://doi.org/10.1042/BJ20060725

Research output: Contribution To Journal



Hayes, JD & Mc Mahon, M 2006,

'The double-edged sword of Nrf2: subversion of redox homeostasis during the evolution of cancer' Molecular Cell, vol. 21, no. 6, pp. 732-4.
https://doi.org/10.1016/j.molcel.2006.03.004

Research output: Contribution To Journal



Mc Mahon, M, Thomas, N, Itoh, K, Yamamoto, M & Hayes, JD 2006,

'Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2-Keap1 complex' Journal of Biological Chemistry, vol. 281, no. 34, pp. 24756-68.
https://doi.org/10.1074/jbc.M601119200

Research output: Contribution To Journal



Wang, XJ, Hayes, JD & Wolf, CR 2006,

'Generation of a stable antioxidant response element-driven reporter gene cell line and its use to show redox-dependent activation of Nrf2 by cancer chemotherapeutic agents' Cancer Research, vol. 66, no. 22, pp. 10983-94.
https://doi.org/10.1158/0008-5472.CAN-06-2298

Research output: Contribution To Journal



Blackburn, AC, Matthaei, KI, Lim, C, Taylor, MC, Cappello, JY, Hayes, JD, Anders, MW & Board, PG 2006,

'Deficiency of glutathione transferase zeta causes oxidative stress and activation of antioxidant response pathways' Molecular Pharmacology, vol. 69, no. 2, pp. 650-7.
https://doi.org/10.1124/mol.105.018911

Research output: Contribution To Journal



Devling, TWP, Lindsay, CD, Mc Lellan, LI, Mc Mahon, M & Hayes, JD 2005,

'Utility of si RNA against Keap1 as a strategy to stimulate a cancer chemopreventive phenotype' Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 20, pp. 7280-7285A.
https://doi.org/10.1073/pnas.0501475102

Research output: Contribution To Journal



Hayes, JD, Flanagan, JU & Jowsey, IR 2005,

'Glutathione transferases' Annual Review of Pharmacology and Toxicology, vol. 45, pp. 51-88.
https://doi.org/10.1146/annurev.pharmtox.45.120403.095857

Research output: Contribution To Journal



Katoh, Y, Iida, K, Kang, M-I, Kobayashi, A, Mizukami, M, Tong, KI, Mc Mahon, M, Hayes, JD, Itoh, K & Yamamoto, M 2005,

'Evolutionary conserved N-terminal domain of Nrf2 is essential for the Keap1-mediated degradation of the protein by proteasome' Archives of Biochemistry and Biophysics, vol. 433, no. 2, pp. 342-50.
https://doi.org/10.1016/j.abb.2004.10.012

Research output: Contribution To Journal



Mannervik, B, Board, PG, Hayes, JD, Listowsky, I & Pearson, WR 2005,

Nomenclature for mammalian soluble glutathione transferases. in H Sies & L Packer (eds), Gluthione transferases and gamma-glutamyl transpeptidases. Methods in Enzymology, vol. 401, Academic Press, pp. 1-8.
https://doi.org/10.1016/S0076-6879(05)01001-3

Research output: Contribution To Book Anthology



Mc Walter, GK, Higgins, LG, Mc Lellan, LI, Henderson, CJ, Song, L, Thornalley, PJ, Itoh, K, Yamamoto, M & Hayes, JD 2004,

'Transcription factor Nrf2 is essential for induction of NAD(P)H:quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates' Journal of Nutrition, vol. 134, no. 12, pp. 3499S-3506S.

Research output: Contribution To Journal



Thomson, RE, Bigley, AL, Foster, JR, Jowsey, IR, Elcombe, CR, Orton, TC & Hayes, JD 2004,

'Tissue-specific expression and subcellular distribution of murine glutathione S-transferase class kappa' Journal of Histochemistry & Cytochemistry, vol. 52, no. 5, pp. 653-662.
https://doi.org/10.1177/002215540405200509

Research output: Contribution To Journal



Mc Mahon, M, Thomas, N, Itoh, K, Yamamoto, M & Hayes, JD 2004,

'Redox-regulated turnover of Nrf2 is determined by at least two separate protein domains, the redox-sensitive Neh4 degron and the redox-insensitive Neh6 degron' Journal of Biological Chemistry, vol. 279, no. 30, pp. 31556-67.
https://doi.org/10.1074/jbc.M403061200

Research output: Contribution To Journal



Nioi, P & Hayes, JD 2004,

'Contribution of NAD(P)H:quinone oxidoreductase 1 to protection against carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine zipper and the arylhydrocarbon receptor basic helix-loop-helix transcription factors' Mutation Research, vol. 555, no. 1-2, pp. 149-71.
https://doi.org/10.1016/j.mrfmmm.2004.05.023

Research output: Contribution To Journal



Goldring, CEP, Kitteringham, NR, Elsby, R, Randle, LE, Clement, YN, Williams, DP, Mc Mahon, M, Hayes, JD, Itoh, K, Yamamoto, M & Park, BK 2004,

'Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 mice' Hepatology, vol. 39, no. 5, pp. 1267-76.
https://doi.org/10.1002/hep.20183

Research output: Contribution To Journal



Mathers, J, Fraser, JA, Mc Mahon, M, Saunders, RDC, Hayes, JD & Mc Lellan, LI 2004,

'Antioxidant and cytoprotective responses to redox stress' Biochemical Society Symposium, no. 71, pp. 157-76.

Research output: Contribution To Journal



Sherratt, PJ, Mc Lellan, LI & Hayes, JD 2003,

'Positive and negative regulation of prostaglandin E2 biosynthesis in human colorectal carcinoma cells by cancer chemopreventive agents' Biochemical Pharmacology, vol. 66, no. 1, pp. 51-61.
https://doi.org/10.1016/S0006-2952(03)00206-5

Research output: Contribution To Journal



Mc Mahon, M, Itoh, K, Yamamoto, M & Hayes, JD 2003,

'Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression' Journal of Biological Chemistry, vol. 278, no. 24, pp. 21592-21600.
https://doi.org/10.1074/jbc.M300931200

Research output: Contribution To Journal



Nioi, P, Mc Mahon, M, Itoh, K, Yamamoto, M & Hayes, JD 2003,

'Identification of a novel Nrf2-regulated antioxidant response element (ARE) in the mouse NAD(P)H:quinone oxidoreductase 1 gene: reassessment of the ARE consensus sequence' Biochemical Journal, vol. 374, no. Pt 2, pp. 337-48.
https://doi.org/10.1042/BJ20030754

Research output: Contribution To Journal



Jowsey, IR, Jiang, Q, Itoh, K, Yamamoto, M & Hayes, JD 2003,

'Expression of the aflatoxin B1-8,9-epoxide-metabolizing murine glutathione S-transferase A3 subunit is regulated by the Nrf2 transcription factor through an antioxidant response element' Molecular Pharmacology, vol. 64, no. 5, pp. 1018-28.
https://doi.org/10.1124/mol.64.5.1018

Research output: Contribution To Journal



Ellis, EM, Slattery, CM & Hayes, JD 2003,

'Characterization of the rat aflatoxin B1 aldehyde reductase gene, AKR7A1. Structure and chromosomal localization of AKR7A1 as well as identification of antioxidant response elements in the gene promoter' Carcinogenesis, vol. 24, no. 4, pp. 727-37.
https://doi.org/10.1093/carcin/bgg016

Research output: Contribution To Journal



Jowsey, IR, Thomson, RE, Orton, TC, Elcombe, CR & Hayes, JD 2003,

'Biochemical and genetic characterization of a murine class Kappa glutathione S-transferase' Biochemical Journal, vol. 373, no. Pt 2, pp. 559-69.
https://doi.org/10.1042/BJ20030415

Research output: Contribution To Journal



Jowsey, IR, Murdock, PR, Moore, GBT, Murphy, GJ, Smith, SA & Hayes, JD 2003,

'Prostaglandin D2 synthase enzymes and PPARγ are co-expressed in mouse 3T3-L1 adipocytes and human tissues' Prostaglandins & Other Lipid Mediators, vol. 70, no. 3-4, pp. 267-84.
https://doi.org/10.1016/S0090-6980(02)00134-X

Research output: Contribution To Journal



Cobbe, SC, Scobie, GC, Pohler, E, Hayes, JD, Kernohan, NM & Dillon, JF 2003,

'Alteration of glutathione S-transferase levels in Barrett's metaplasia compared to normal oesophageal epithelium' European Journal of Gastroenterology & Hepatology, vol. 15, no. 1, pp. 41-47.

Research output: Contribution To Journal



Jowsey, IR, Smith, SA & Hayes, JD 2003,

'Expression of the murine glutathione S-transferase α3 (GSTA3) subunit is markedly induced during adipocyte differentiation: activation of the GSTA3 gene promoter by the pro-adipogenic eicosanoid 15-deoxy-Δ12,14-prostaglandin J2' Biochemical and Biophysical Research Communications, vol. 312, no. 4, pp. 1226-35.
https://doi.org/10.1016/j.bbrc.2003.11.068

Research output: Contribution To Journal



Chanas, SA, Jiang, Q, Mc Mahon, M, Mc Walter, GK, Mc Lellan, LI, Elcombe, CR, Henderson, CJ, Wolf, CR, Moffat, GJ, Itoh, K, Yamamoto, M & Hayes, JD 2002,

'Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice' Biochemical Journal, vol. 365, no. Pt 2, pp. 405-16.
https://doi.org/10.1042/BJ20020320

Research output: Contribution To Journal



Kelly, VP, Sherratt, PJ, Crouch, DH & Hayes, JD 2002,

'Novel homodimeric and heterodimeric rat g-hydroxybutyrate synthases that associate with the Golgi apparatus define a distinct subclass of aldo-keto reductase 7 family proteins' Biochemical Journal, vol. 366, no. Pt 3, pp. 847-61.
https://doi.org/10.1042/BJ20020342

Research output: Contribution To Journal



Sherratt, PJ, Williams, S, Foster, J, Kernohan, N, Green, T & Hayes, JD 2002,

'Direct comparison of the nature of mouse and human GST T1-1 and the implications on dichloromethane carcinogenicity' Toxicology and Applied Pharmacology, vol. 179, no. 2, pp. 89-97.
https://doi.org/10.1006/taap.2002.9348

Research output: Contribution To Journal



Hayes, J 2001,

'Expression of rat aldehyde reductase AKR7A1: influence of age and sex, and tissue-specific inducibility' Biochemical Pharmacology, vol. 62, no. 11, 11728387, pp. 1511-1519.
https://doi.org/10.1016/S0006-2952(01)00771-7

Research output: Contribution To Journal



Jowsey, IR, Thomson, AM, Flanagan, JU, Murdock, PR, Moore, GBT, Meyer, DJ, Murphy, GJ, Smith, SA & Hayes, JD 2001,

'Mammalian class Sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases' Biochemical Journal, vol. 359, no. 3, pp. 507-516.
https://doi.org/10.1042/bj3590507

Research output: Contribution To Journal



Picklo, MJ, Olson, SJ, Hayes, J, Markesbery, WR & Montine, TJ 2001,

'Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerative disease' Brain Research, vol. 916, no. 1-2, pp. 229-238.
https://doi.org/10.1016/S0006-8993(01)02897-9

Research output: Contribution To Journal



Bonnesen, C, Eggleston, IM & Hayes, JD 2001,

'Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines' Cancer Research, vol. 61, no. 16, pp. 6120-6130.

Research output: Contribution To Journal



Guengerich, FP, Cai, H, Mc Mahon, M, Hayes, JD, Sutter, TR, Groopman, JD, Deng, Z & Harris, TM 2001,

'Reduction of Aflatoxin B1 Dialdehyde by Rat and Human Aldo-keto Reductases' Chemical Research in Toxicology, vol. 14, no. 6, pp. 727-737.
https://doi.org/10.1021/tx010005p

Research output: Contribution To Journal



Mc Mahon, M, Itoh, K, Yamamoto, M, Chanas, SA, Henderson, CJ, Mc Lellan, LI, Wolf, CR, Cavin, C & Hayes, JD 2001,

'The Cap ‘n’ Collar Basic Leucine Zipper Transcription Factor Nrf2 (NF-E2 p45-related Factor 2) Controls Both Constitutive and Inducible Expression of Intestinal Detoxification and Glutathione Biosynthetic Enzymes' Cancer Research, vol. 61, no. 8, pp. 3299-3307.

Research output: Contribution To Journal



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