Dr Ruan Elliott

Associate Dean (Doctoral College); Senior Lecturer in Nutrition
+44 (0)1483 683843
21 AY 03

Academic and research departments

School of Biosciences.



1994-2009: Senior Scientist, Institute of Food Research Norwich

1992-1994: Post-doctoral Research Fellow, University of British Columbia, Canada

1992: PhD in Nutritional Metabolism (University of Surrey)

1988: BA (Hons) Natural Sciences (University of Cambridge)

Research interests

  • Nutritional modulation of DNA damage:repair
  • Application of functional genomic techniques in nutrition: optimising nutrigenomic study designs, developing concepts for risk-benefit analysis and defining optimal nutrition
  • Defining optimal micronutrient intakes and modelling homeostatic mechanisms (with in particular interest in iron, copper, selenium and zinc)

Research collaborations

Inter-faculty collaborations:“Proof of Principle for Resolving Controversies in Mineral Transport” project funded under the Systems and Life Ideas Exchange of the Models programme of the Mathematics in Life and Social Sciences (MILES) project with Drs Matthew Turner and Gianne Derks (Mathematics), Dr Bernadette Moore (Nutritional Sciences) and Dr Theresa Hague (Post Graduate Medical School)

"Mathematical modelling of the repair dynamics of alkylatation damage to DNA in mammalian cells" project funded under the Discipline Hops programme of the Models and Mathematics in Life and Social Sciences (MILES) programme with Dr Philip Aston (Mathematics) and Dr Lisiane Meira (Biochemical Sciences)

National collaborations:“Impact of non-digestible carbohydrates on biomarkers of GI health: a human intervention study” BBSRC Diet and Health Research Industry Club (DRINC) project (BB/H005021/1) with Professor John Mathers (University of Newcastle) and Professor Ian Johnson (Institute of Food Research, Norwich)

International collaborations:Network board member and Work Package Leader for the European Nutrigenomics Organisation (NuGO, www.nugo.org), a Network of Excellence funded under the European Commission's Framework Programme 6.


Louise R Durrant, Giselda Bucca, Andrew Hesketh, Carla Möller-Levet, Laura Tripkovic, Huihai Wu, Kathryn H Hart, John C Mathers, Ruan M Elliott, Susan A Lanham-New, Colin P Smith (2022)Vitamins D 2 and D 3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome, In: Frontiers in immunology13790444

Vitamin D is best known for its role in maintaining bone health and calcium homeostasis. However, it also exerts a broad range of extra-skeletal effects on cellular physiology and on the immune system. Vitamins D and D share a high degree of structural similarity. Functional equivalence in their vitamin D-dependent effects on human physiology is usually assumed but has in fact not been well defined experimentally. In this study we seek to redress the gap in knowledge by undertaking an in-depth examination of changes in the human blood transcriptome following supplementation with physiological doses of vitamin D and D . Our work extends a previously published randomized placebo-controlled trial that recruited healthy white European and South Asian women who were given 15 µg of vitamin D or D daily over 12 weeks in wintertime in the UK (Nov-Mar) by additionally determining changes in the blood transcriptome over the intervention period using microarrays. An integrated comparison of the results defines both the effect of vitamin D or D on gene expression, and any influence of ethnic background. An important aspect of this analysis was the focus on the changes in expression from baseline to the 12-week endpoint of treatment each individual, harnessing the longitudinal design of the study. Whilst overlap in the repertoire of differentially expressed genes was present in the D or D -dependent effects identified, most changes were specific to either one vitamin or the other. The data also pointed to the possibility of ethnic differences in the responses. Notably, following vitamin D supplementation, the majority of changes in gene expression reflected a down-regulation in the activity of genes, many encoding pathways of the innate and adaptive immune systems, potentially shifting the immune system to a more tolerogenic status. Surprisingly, gene expression associated with type I and type II interferon activity, critical to the innate response to bacterial and viral infections, differed following supplementation with either vitamin D or vitamin D , with only vitamin D having a stimulatory effect. This study suggests that further investigation of the respective physiological roles of vitamin D and vitamin D is warranted.

Laura Tripkovic, LR Wilson, Kathryn Hart, Sigurd Johnsen, Simon de Lusignan, CP Smith, G Bucca, S Penson, G Chope, Ruan Elliott, E Hypponen, J L Berry, Susan Lanham-New (2017)Daily supplementation with 15 mg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial, In: American Journal of Clinical Nutrition106(2)pp. 481-490 American Society for Nutrition

Background: There are conflicting views in the literature as to whether vitamin D2 and vitamin D3 are equally effective in increasing and maintaining serum concentrations of 25-hydroxyvitamin D [25(OH)D], particularly at lower doses of vitamin D. Objective: We aimed to investigate whether vitamin D2 or vitamin D3 fortified in juice or food, at a relatively low dose of 15 μg/d, was effective in increasing serum total 25(OH)D and to compare their respective efficacy in South Asian and white European women over the winter months within the setting of a large randomized controlled trial. Design: A randomized, double-blind, placebo-controlled food-fortification trial was conducted in healthy South Asian and white European women aged 20–64 y (n = 335; Surrey, United Kingdom) who consumed placebo, juice supplemented with 15 μg vitamin D2, biscuit supplemented with 15 μg vitamin D2, juice supplemented with 15 μg vitamin D3, or biscuit supplemented with 15 μg vitamin D3 daily for 12 wk. Serum 25(OH)D was measured by liquid chromatography–tandem mass spectrometry at baseline and at weeks 6 and 12 of the study. Results: Postintervention in the 2 ethnic groups combined, both the vitamin D3 biscuit and the vitamin D3 juice groups showed a significantly greater absolute incremental change (Δ) in total 25(OH)D when compared with the vitamin D2 biscuit group [Δ (95% CI): 15.3 nmol/L (7.4, 23.3 nmol/L) (P < 0.0003) and 16.0 nmol/L (8.0, 23.9 nmol/L) ( P < 0.0001)], the vitamin D2 juice group [Δ (95% CI): 16.3 nmol/L (8.4, 24.2 nmol/L) (P < 0.0001) and 16.9 nmol/L (9.0, 24.8 nmol/L) (P < 0.0001)], and the placebo group [Δ (95% CI): 42.3 nmol/L (34.4, 50.2 nmol/L) (P < 0.0001) and 42.9 nmol/L (35.0, 50.8 nmol/L) (P < 0.0002)]. Conclusions: With the use of a daily dose of vitamin D relevant to public health recommendations (15 μg) and in vehicles relevant to food-fortification strategies, vitamin D3 was more effective than vitamin D2 in increasing serum 25(OH)D in the wintertime. Vitamin D3 may therefore be a preferential form to optimize vitamin D status within the general population. This trial was registered at www.controlled-trials.com as ISRCTN23421591.

RM Elliott, IT Johnson (2007)Nutrigenomic approaches for obesity research, In: OBESITY REVIEWS8pp. 77-81 BLACKWELL PUBLISHING
B de Roos, SJ Duthie, ACJ Polley, F Mulholland, FG Bouwman, C Heim, GJ Rucklidge, IT Johnson, EC Mariman, H Daniel, RM Elliott (2008)Proteomic methodological recommendations for studies involving human plasma, platelets, and peripheral blood mononuclear cells, In: JOURNAL OF PROTEOME RESEARCH7(6)pp. 2280-2290 AMER CHEMICAL SOC
BAV Thompson, PA Sharp, RM Elliott, SJ Fairweather-Tait (2010)The inhibitory effect of calcium on iron absorption may be related to translocation of DMT-1 at the apical membrane of enterocytes, In: J Agric Food Chem58(14)pp. 8414-8417
P Rocca-Serra, RM Elliott (2006)Data storage: bringing us a step closer to data sharing?, In: BRITISH JOURNAL OF NUTRITION95(6)pp. 1237-1239 CABI PUBLISHING
RM Elliott, B de Roos, SJ Duthie, FG Bouwman, I Rubio-Aliaga, LK Crosley, C Mayer, AC Polley, C Heim, SL Coort, CT Evelo, F Mulholland, H Daniel, EC Mariman, IT Johnson (2014)Transcriptome analysis of peripheral blood mononuclear cells in human subjects following a 36 h fast provides evidence of effects on genes regulating inflammation, apoptosis and energy metabolism, In: GENES AND NUTRITION9(6)ARTN 4 SPRINGER

There is growing interest in the potential health benefits of diets that involve regular periods of fasting. While animal studies have provided compelling evidence that feeding patterns such as alternate-day fasting can increase longevity and reduce incidence of many chronic diseases, the evidence from human studies is much more limited and equivocal. Additionally, although several candidate processes have been proposed to contribute to the health benefits observed in animals, the precise molecular mechanisms responsible remain to be elucidated. The study described here examined the effects of an extended fast on gene transcript profiles in peripheral blood mononuclear cells from ten apparently healthy subjects, comparing transcript profiles after an overnight fast, sampled on four occasions at weekly intervals, with those observed on a single occasion after a further 24 h of fasting. Analysis of the overnight fasted data revealed marked inter-individual differences, some of which were associated with parameters such as gender and subject body mass. For example, a striking positive association between body mass index and the expression of genes regulated by type 1 interferon was observed. Relatively subtle changes were observed following the extended fast. Nonetheless, the pattern of changes was consistent with stimulation of fatty acid oxidation, alterations in cell cycling and apoptosis and decreased expression of key pro-inflammatory genes. Stimulation of fatty acid oxidation is an expected response, most likely in all tissues, to fasting. The other processes highlighted provide indications of potential mechanisms that could contribute to the putative beneficial effects of intermittent fasting in humans.

B Thompson, P Sharp, RM Elliott, S Al-Mutairi, SJ Fairweather-Tait (2010)Development of a modified Caco-2 cell model system for studying iron availability in eggs, In: J Agric Food Chem58(6)pp. 3833-3839
B van Ommen, A El-Sohemy, J Hesketh, J Kaput, M Fenech, C Evelo, H McArdle, J Bouwman, G Lietz, J Mathers, S Fairweather-Tait, H van Kranen, R Elliott, S Wopereis, LR Ferguson, C Meplan, G Perozzi, L Allen, D Revero, The Micronutrient Genomics Project Working Group (2010)The micronutrient genomics project: creating a community driven knowledge base for micronutrient research, In: Genes Nutr5(4)pp. 285-296
JJ Eady, YM Wormstone, SJ Heaton, B Hilhorst, RM Elliott (2015)Differential effects of basolateral and apical iron supply on iron transport in Caco-2 cells, In: Genes and Nutrition10(3)ARTN 1 SPRINGER

Iron homeostasis in the human body is maintained primarily through regulation of iron absorption in the duodenum. The liver peptide hepcidin plays a central role in this regulation. Additionally, expression and functional control of certain components of the cellular iron transport machinery can be influenced directly by the iron status of enterocytes. The significance of this modulation, relative to the effects of hepcidin, and the comparative effects of iron obtained directly from the diet and/or via the bloodstream are not clear. The studies described here were performed using Caco-2 cell monolayers as a model of intestinal epithelium, to compare the effects of iron supplied in physiologically relevant forms to either the apical or basolateral surfaces of the cells. Both sources of iron provoked increased cellular ferritin content, indicating iron uptake from both sides of the cells. Supply of basolateral transferrin-bound iron did not affect subsequent iron transport across the apical surface, but reduced iron transport across the basolateral membrane. In contrast, the apical iron supply led to subsequent reduction in iron transport across the apical cell membrane without altering iron export across the basolateral membrane. The apical and basolateral iron supplies also elicited distinct effects on the expression and subcellular distribution of iron transporters. These data suggest that, in addition to the effects of cellular iron status on the expression of iron transporter genes, different modes and direction of iron supply to enterocytes can elicit distinct functional effects on iron transport.

JJ Eady, GM Wortley, YM Wormstone, JC Hughes, SB Astley, RJ Foxall, JF Doleman, RM Elliott (2005)Variation in gene expression profiles of peripheral blood mononuclear cells from healthy volunteers, In: Physiological Genomics22(3)pp. 402-411
SJ Heaton, JJ Eady, ML Parker, KL Gotts, JR Dainty, SJ Fairweather-Tait, HJ McArdle, KS Srai, RM Elliott (2008)The use of BeWo cells as an in vitro model for placental iron transport, In: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY295(5)pp. C1445-C1453 AMER PHYSIOLOGICAL SOC
RM Elliott (2008)Transcriptomics and micronutrient research., In: Br J Nutr99 Suppp. S59-S65

This review examines the extent to which transcriptomic methods have lived up to their promise in the context of nutrition research, placing particular emphasis on examples from micronutrient research. A case is made that the high quality platform technologies now available, together with established standards and systems for data storage and exchange and powerful new methods of data analysis, mean that microarrays have reached a level of technical maturity at which they can be exploited to their full potential. In the context of nutrition and micronutrient research, transcriptomic methods have already been widely applied, albeit primarily in studies using cell lines and animal models. Using this type of approach, a multitude of genes regulated at the mRNA level by dietary components has been identified and this, in turn, has provided new insights into the biological processes affected by nutritional parameters. Evidence from the very limited number of published transcriptomics-based nutritional studies performed in human volunteers suggests that, with appropriate study design, it is feasible to apply transcriptomic methods successfully in dietary intervention trials. On the other hand, gene expression-based biomarker development still poses a major challenge. Here the use of expression profile 'signatures', rather than single genes, may provide a solution. Approaches designed to identify such 'signatures' are being developed and tested widely, primarily in the context of medical research. The applicability and power of such approaches should also be evaluated in the context of nutrition.

R Hurst, RM Elliott, AJ Goldson, SJ Fairweather-Tait (2008)Se-methylselenocysteine alters collagen gene and protein expression in human prostate cells., In: Cancer Lett269(1)pp. 117-126

The anti-cancer activity of selenium is dose-dependent and species-specific but the mechanism is unclear. Se-methylselenocysteine (MSC), found in selenium-enriched alliums, is one of the most potent forms. We exposed two human prostate cell lines (LNCaP clone FGC and PNT1A) to nutritionally relevant doses of MSC and selenite, ranging from deficient to the equivalent of selenium supplementation in humans. The cells were adapted for one month to attain steady-state selenium status. Two microarray platforms, an in-house printed microarray (14,000 genes) and the Affymetrix U133A array (22,000 genes) were used to probe the molecular effects of selenium dose and form and several selenium-responsive genes were identified, many of which have been ascribed to cancer cell growth and progression. In response to MSC supplementation, the expression of 23 genes changed significantly, including several collagen genes. Quantitative RT-PCR assays were designed and optimized for four of the collagen genes to validate array data. Significant decreases in expression of collagen type I alpha 1 (COL1A1), COL1A2 and COL7A1 genes were observed in cells adapted to MSC supplementation compared to the control and selenite exposed cells. There were significant increases in genes encoding other types of collagen, including significant increases in COL6A1 and COL4A5 in response to MSC dose. Functional changes in collagen type I protein expression in response to MSC were confirmed by ELISA. This study reveals for the first time that MSC can alter the expression of several types of collagen and thus potentially modulate the extracellular matrix and stroma, which may at least partially explain the anti-cancer activity of MSC.

Fahad A. Alhumaydhi, Debora de O. Lopes, Diana L. Bordin, Abdullah S. M. Aljohani, Cameron B. Lloyd, Michael D. McNicholas, Larissa Milano, Clara F. Charlier, Izabel Villela, João Antonio P. Henriques, Kathryn E. Plant, Ruan M. Elliott, Lisiane B. Meira (2020)Alkyladenine DNA glycosylase deficiency uncouples alkylation-induced strand break generation from PARP-1 activation and glycolysis inhibition, In: Scientific Reports10(1) Nature Publishing Group

DNA alkylation damage is repaired by base excision repair (BER) initiated by alkyladenine DNA glycosylase (AAG). Despite its role in DNA repair, AAG-initiated BER promotes cytotoxicity in a process dependent on poly (ADP-ribose) polymerase-1 (PARP-1); a NAD+-consuming enzyme activated by strand break intermediates of the AAG-initiated repair process. Importantly, PARP-1 activation has been previously linked to impaired glycolysis and mitochondrial dysfunction. However, whether alkylation affects cellular metabolism in the absence of AAG-mediated BER initiation is unclear. To address this question, we temporally profiled repair and metabolism in wild-type and Aag−I− cells treated with the alkylating agent methyl methanesulfonate (MMS). We show that, although Aag−I− cells display similar levels of alkylation-induced DNA breaks as wild type, PARP-1 activation is undetectable in AAG-deficient cells. Accordingly, Aag−I− cells are protected from MMS-induced NAD+ depletion and glycolysis inhibition. MMS-induced mitochondrial dysfunction, however, is AAG-independent. Furthermore, treatment with FK866, a selective inhibitor of the NAD+ salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT), synergizes with MMS to induce cytotoxicity and Aag−I− cells are resistant to this combination FK866 and MMS treatment. Thus, AAG plays an important role in the metabolic response to alkylation that could be exploited in the treatment of conditions associated with NAD+ dysregulation.

L Wilson, K Hart, R Elliott, CP Smith, G Bucca, S Penson, G Chope, E Hypponen, J Berry, S Lanham-New, L Tripkovic (2015)The D2-D3 Study: comparing the efficacy of 15 mu g/d vitamin D2 vs. D3 in raising vitamin D status in both South Asian and Caucasian women, and the ethical implications of placebo treatment, In: PROCEEDINGS OF THE NUTRITION SOCIETY74(OCE1)pp. E116-E116 CAMBRIDGE UNIV PRESS
RM Elliott, LM Morgan, J Tredger, J Wright (1994)The effects of cereal source and processing on the metabolic responses to commercially available breakfast cereals and breads, In: International Journal of Food Sciences and Nutrition45(3)pp. 217-222
AJ Watson, J Worley, RM Elliott, DJ Jeenes, DB Archer (2000)Cloning stress-induced genes from Aspergillus niger using polymerase chain reaction-augmented subtractive hybridization, In: Analytical Biochemistry277(1)pp. 162-165
Nikunj Shah, Lisiane B. Meira, Ruan M. Elliott, Stephen P. Hoole, Nick E. West, Adam J. Brown, Martin R. Bennett, Hector M. Garcia-Garcia, Kayode O. Kuku, Kazuhiro Dan, Paul Kolm, Mark Mariathas, Nick Curzen, Michael Mahmoudi (2019)DNA damage and repair in patients with coronary artery disease: Correlation with plaque morphology using optical coherence tomography (DECODE study), In: Cardiovascular Revascularization Medicine20(9)pp. 812-818 Elsevier

Objective The aim of this study was to examine DNA ligase activity and expression of DNA damage response pathway (DDR) genes in patients with stable angina (SA) and non-ST elevation myocardial infarction (NSTEMI) and determine whether they correlate with plaque morphology. Background Patients with coronary artery disease (CAD) have evidence of deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear cells (PBMCs). It is unclear whether this represents excess damage or defective DNA repair activity. Methods DNA ligase activity and the expression of 22 DDR genes were measured in PBMCs of patients (both SA (n = 47) and NSTEMI (n = 42)) and in age and gender-matched controls (n = 35). Target lesion anatomical assessment was undertaken with frequency domain optical coherent tomography. Results DNA ligase activity was different across the three groups of patients (control = 119 ± 53, NSTEMI = 115.6 ± 85.1, SA = 81 ± 55.7 units/g of nuclear protein; ANOVA p = 0.023). Pair wise comparison demonstrated that this significance is due to differences between the control and SA patients (p = 0.046). Genes involved in double strand break repair and nucleotide excision repair pathways were differentially expressed in patients with SA and NSTEMI. In SA patients, fibrocalcific plaques were strongly associated with GTSE1, DDB1, MLH3 and ERCC1 expression. By contrast, in NSTEMI patients the strongest association was observed between fibrous plaques and ATM and XPA expression. Conclusion PBMCs from patients with CAD exhibit differences in DNA ligase activity and expression of DDR genes. Expression levels of certain DDR genes are strongly associated with plaque morphology and may play a role in plaque development and progression.

SB Astley, RM Elliott (2007)The European Nutrigenomics Organisation: linking genomics, nutrition and health research, In: JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE87(7)pp. 1180-1184 JOHN WILEY & SONS LTD
LK Crosley, SJ Duthie, AC Polley, FG Bouwman, C Heim, F Mulholland, G Horgan, IT Johnson, EC Mariman, RM Elliott, H Daniel, B de Roos (2009)Variation in protein levels obtained from human blood cells and biofluids for platelet, peripheral blood mononuclear cell, plasma, urine and saliva proteomics, In: GENES AND NUTRITION4(2)pp. 95-102 SPRINGER
I Rubio-Aliaga, B de Roos, SJ Duthie, LK Crosley, C Mayer, G Horgan, IJ Colquhoun, G Le Gall, F Huber, W Kremer, M Rychlik, S Wopereis, B van Ommen, G Schmidt, C Heim, FG Bouwman, EC Mariman, F Mulholland, IT Johnson, AC Polley, RM Elliott, H Daniel (2011)Metabolomics of prolonged fasting in humans reveals new catabolic markers, In: METABOLOMICS7(3)pp. 375-387 SPRINGER
P Garosi, C De Filippo, M van Erk, P Rocca-Serra, SA Sansone, R Elliott (2005)Defining best practice for microarray analyses in nutrigenomic studies, In: BRITISH JOURNAL OF NUTRITION93(4)pp. 425-432 CABI PUBLISHING
M Baccini, EM Bachmaier, A Biggeri, MV Boekschoten, FG Bouwman, L Brennan, R Caesar, S Cinti, SL Coort, K Crosley, H Daniel, CA Drevon, S Duthie, L Eijssen, RM Elliott, M van Erk, C Evelo, M Gibney, C Heim, GW Horgan, IT Johnson, T Kelder, R Kleemann, T Kooistra, MP van Iersel, EC Mariman, C Mayer, G McLoughlin, M Müller, F Mulholland, B van Ommen, AC Polley, E Pujos-Guillot, I Rubio-Aliaga, HM Roche, B de Roos, M Sailer, G Tonini, LM Williams, N de Wit, NuGO PPS Team (2008)The NuGO proof of principle study package: a collaborative research effort of the European Nutrigenomics Organisation., In: Genes Nutr3(3-4)pp. 147-151
R Elliott, C Pico, Y Dommels, I Wybranska, J Hesketh, J Keijer (2007)Nutrigenomic approaches for benefit-risk analysis of foods and food components: defining markers of health, In: BRITISH JOURNAL OF NUTRITION98(6)pp. 1095-1100 CAMBRIDGE UNIV PRESS
Eleanor Healing, Clara. F Charlier, Lisie Meira, Ruan Elliott (2019)A panel of colorimetric assays to measure enzymatic activity in the base excision DNA repair pathway, In: Nucleic Acids Research47(11)e61 Oxford University Press

DNA repair is essential for the maintenance of genomic integrity, and evidence suggest that interindividual variation in DNA repair efficiency maycontribute to disease risk. However, robust assays suitable for quantitative determination of DNA repair capacity in large cohort and clinical trials are needed to evaluate these apparent associations fully. We describe here a set of microplate-based oligonucleotide assays for high-throughput, non-radioactiveand quantitative determination of repair enzyme activity at individual steps and over multiple steps of the DNA base excision repair pathway. The assays are highly sensitive: using HepG2 nuclear extract, enzyme activities were quantifiable at concentrationsof 0.0002 to 0.181 g per reaction, depending on the enzyme being measured. Assay coefficients of variation are comparable with other microplate-based assays. The assay format requires no specialist equipment and has the potential to be extended for analysis of a wide range of DNA repair enzyme activities. As such, these assays hold considerable promise for gaining new mechanistic insights into how DNA repair is related to individual genetics, disease status or progression and other environmental factors and investigating whether DNA repair activities can be used a biomarker of disease risk.

SB Astley, RM Elliott, DB Archer, S Southon (2004)Evidence that dietary supplementation with carotenoids and carotenoid-rich foods modulates the DNA damage: repair balance in human lymphocytes, In: BRITISH JOURNAL OF NUTRITION91(1)pp. 63-72 C A B I PUBLISHING
R Elliott (2005)Mechanisms of genomic and non-genomic actions of carotenoids, In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE1740(2)pp. 147-154 ELSEVIER SCIENCE BV
Eduard Mas Claret, Balqees Al Yahyaei, Shuyu Chu, Ruan M. Elliott, Manuel Imperato, Arnaud Lopez, LISIANE BORGES MEIRA, Brendan J. Howlin, Daniel K. Whelligan (2020)An aza-nucleoside, fragment-like inhibitor of the DNA repair enzyme alkyladenine glycosylase (AAG), In: Bioorganic & Medicinal Chemistry28(11)115507 Elsevier

The DNA repair enzyme AAG has been shown in mice to promote tissue necrosis in response to ischaemic reperfusion or treatment with alkylating agents. A chemical probe inhibitor is required for investigations of the biological mechanism causing this phenomenon and as a lead for drugs that are potentially protective against tissue damage from organ failure and transplantation, and alkylative chemotherapy. Herein, we describe the rationale behind the choice of arylmethylpyrrolidines as appropriate aza-nucleoside mimics for an inhibitor followed by their synthesis and the first use of a microplate-based assay for quantification of their inhibition of AAG. We finally report the discovery of an imidazol-4-ylmethylpyrrolidine as a fragment-sized, weak inhibitor of AAG.

SB Astley, DA Hughes, AJA Wright, RM Elliott, S Southon (2004)DNA damage and susceptibility to oxidative damage in lymphocytes: effects of carotenoids in vitro and in vivo, In: BRITISH JOURNAL OF NUTRITION91(1)pp. 53-61 C A B I PUBLISHING
B van Ommen, J Keijer, R Kleemann, R Elliott, CA Drevon, H McArdle, M Gibney, M Muller (2008)The challenges for molecular nutrition research 2: quantification of the nutritional phenotype, In: GENES AND NUTRITION3(2)pp. 51-59 SPRINGER
SB Astley, RM Elliott (2005)The European Nutrigenomics Organisation: linking genomics, nutrition and health research (NuGO), In: TRENDS IN FOOD SCIENCE & TECHNOLOGY16(4)pp. 155-161 ELSEVIER SCIENCE LONDON
R Elliott, TJ Ong (2002)Science, medicine, and the future - Nutritional genomics, In: BRITISH MEDICAL JOURNAL324(7351)pp. 1438-1442 B M J PUBLISHING GROUP
J Kaput, JM Ordovas, L Ferguson, B van Ommen, RL Rodriguez, L Allen, BN Ames, K Dawson, B German, R Krauss, W Malyj, MC Archer, S Barnes, A Bartholomew, R Birk, P van Bladeren, KJ Bradford, KH Brown, R Caetano, D Castle, R Chadwick, S Clarke, K Clement, CA Cooney, D Corella, IBM da Cruz, H Daniel, T Duster, SOE Ebbesson, R Elliott, S Fairweather-Tait, J Felton, M Fenech, JW Finley, N Fogg-Johnson, R Gill-Garrison, MJ Gibney, PJ Gillies, JA Gustafsson, JL Hartmann, L He, JK Hwang, JP Jais, YS Jang, H Joost, C Junien, M Kanter, WA Kibbe, B Koletzko, BR Korf, K Kornman, DW Krempin, D Langin, DR Lauren, JH Lee, GA Leveille, SJ Lin, J Mathers, M Mayne, W McNabb, JA Milner, P Morgan, M Muller, Y Nikolsky, F van der Ouderaa, T Park, N Pensel, F Perez-Jimenez, K Poutanen, M Roberts, WHM Saris, G Schuster, AN Shelling, AP Simopoulos, S Southon, ES Tai, B Towne, P Trayhurn, R Uauy, WJ Visek, C Warden, R Weiss, J Wiencke, J Winkler, GL Wolff, ZW Xi, JD Zucker (2005)The case for strategic international alliances to harness nutritional genomics for public and personal health, In: BRITISH JOURNAL OF NUTRITION94(5)pp. 623-632 CAMBRIDGE UNIV PRESS
SB Astley, RM Elliott, DB Archer, S Southon (2002)Increased cellular carotenoid levels reduce the persistence of DNA single-strand breaks after oxidative challenge, In: NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL43(2)pp. 202-213 LAWRENCE ERLBAUM ASSOC INC
B van Ommen, J Bouwman, LO Dragsted, CA Drevon, R Elliott, P de Groot, J Kaput, JC Mathers, M Mueller, F Pepping, J Saito, A Scalbert, M Radonjic, P Rocca-Serra, A Travis, S Wopereis, CT Evelo (2010)Challenges of molecular nutrition research 6: the nutritional phenotype database to store, share and evaluate nutritional systems biology studies, In: GENES AND NUTRITION5(3)pp. 189-203 SPRINGER
RM Elliott, SB Astley, S Southon, DB Archer (2000)Measurement of cellular repair activities for oxidative DNA damage, In: FREE RADICAL BIOLOGY AND MEDICINE28(9)pp. 1438-1446 PERGAMON-ELSEVIER SCIENCE LTD
Larissa Milano, Clara. F Charlier, Rafaela Andreguetti, THOMAS JAMES COX, Eleanor Healing, Marcos P Thomé, RUAN MICHAEL ELLIOTT, LD Samson, Jean-Yves Masson, G Lenz, João Antonio P Henriques, A Nohturfft, LISIANE BORGES MEIRA (2022)A DNA repair-independent role for alkyladenine DNA glycosylase in alkylation-induced unfolded protein response, In: Proceedings of the National Academy of Sciences - PNAS119(9)e2111404119 PNAS

Alkylating agents damage DNA and proteins and are widely used in cancer chemotherapy. While cellular responses to alkylation-induced DNA damage have been explored, knowledge of how alkylation affects global cellular stress responses is sparse. Here, we examined the effects of the alkylating agent methylmethane sulfonate (MMS) on gene expression in mouse liver, using mice deficient in alkyladenine DNA glycosylase (Aag), the enzyme that initiates the repair of alkylated DNA bases. MMS induced a robust transcriptional response in wild-type liver that included markers of the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) known to be controlled by XBP1, a key UPR effector. Importantly, this response is significantly reduced in the knockout. To investigate how AAG affects alkylation-induced UPR, the expression of UPR markers after MMS treatment was interrogated in human glioblastoma cells expressing different AAG levels. Alkylation induced the UPR in cells expressing AAG; conversely, knockdown compromised UPR induction and led to a defect in XBP1 activation. To verify the requirements for the DNA repair activity of AAG in this response, knockdown cells were complemented with wild-type or with an variant producing a glycosylase-deficient AAG protein. As expected, the glycosylase-defective Aag does not fully protect knockdown cells against MMS-induced cytotoxicity. Remarkably, however, alkylation-induced XBP1 activation is fully complemented by the catalytically inactive AAG enzyme. This work establishes that, besides its enzymatic activity, AAG has noncanonical functions in alkylation-induced UPR that contribute to cellular responses to alkylation.

T Bourdeau, F Spertini, F Raymond, R Audran, L Gosoniu, A Mercenier, S Nutten, C Blanchard, Ruan Elliott (2017)Transcriptomic Analysis of PBMCs from Allergic Patients after Probiotic Treatment, In: Austin Journal of Nutrition and Metabolism4(1)id1046 Austin Publishing Group

Background: Allergic rhinitis is one of the most prevalent manifestation of allergy, affecting over 15% of the population worldwide. Recent published clinical studies have shown that specific probiotics can improveallergic rhinitis clinical symptoms. Findings: In this study, thirty one adult volunteers suffering from allergic rhinitis were enrolled in a crossover study evaluating the efficacy of the consumption of a product containing either L. paracasei-fermented milk or the placebo. Transcriptomic analysis was performed on unstimulated PBMC after each treatment period and analysis was adjusted for the crossover design. No differences were observed between PBMCs from probiotic treated allergen challenged allergic patients and PBMCs from placebo treated allergen challenged allergic patients. Conclusion: This study shows that, in the blood compartment, PBMCs mRNA levels are too stable to mirror the changes of symptoms and alteration of cytokine expressions observed after a treatment with L. paracasei.

MJ Jackson, S Papa, J Bolaños, R Bruckdorfer, H Carlsen, RM Elliott, J Flier, HR Griffiths, S Heales, B Holst, M Lorusso, E Lund, J Øivind Moskaug, U Moser, M Di Paola, MC Polidori, A Signorile, W Stahl, J Viña-Ribes, SB Astley (2002)Antioxidants, reactive oxygen and nitrogen species, gene induction and mitochondrial function., In: Mol Aspects Med23(1-3)pp. 209-285
LJ Dawes, RM Elliott, JR Reddan, YM Wormstone, IM Wormstone (2007)Oligonucleotide microarray analysis of human lens epithelial cells: TGF beta regulated gene expression, In: MOLECULAR VISION13(128-30)pp. 1181-1197 MOLECULAR VISION
MJ Jackson, RM Elliott, E Lund, S Papa, SB Astley (2002)Antioxidants, reactive oxygen and nitrogen species, gene induction and mitochondrial function., In: FREE RADICAL RESEARCH36pp. 14-14
RM Elliott, S Southon, DB Archer (1999)Oxidative insult specifically decreases levels of a mitochondrial transcript, In: Free Radical Biology and Medicine26(5-6)pp. 646-655
J Hesketh, I Wybranska, Y Dommels, M King, R Elliott, C Pico, J Keijer (2006)Nutrient-gene interactions in benefit-risk analysis., In: Br J Nutr95(6)pp. 1232-1236

Individuals respond differently to nutrients and foods. This is reflected in different levels of benefits and risks at the same intake of a nutrient and, consequently, different 'windows of benefit' in terms of nutrient intake. This has led recently to the concept of 'personalised nutrition'. Genetic factors such as single nucleotide polymorphisms may be one source of this inter-individual variation in benefit-risk response to nutrients. In 2004 a European Union-funded network of excellence in the area of nutrigenomics (European Nutrigenomics Organisation; NuGO) organised a workshop on the role of nutrient-gene interactions in determining benefit-risk of nutrients and diet. The major issues discussed at the workshop are presented in the present paper and highlighted with examples from the presentations. The overall consensus was that although genetics provides a new vision where genetic information could in the future be used to provide knowledge on disease predisposition and nutritional requirements, such a goal is still far off and much more research is required before we can reliably include genetic factors in the risk-benefit assessment of nutrients and diets.

NR Shah, L Meira, RM Elliott, PJ Howlett, AJ Brown, M Williams, NE West, S Hoole, M Mahmoudi (2015)DNA repair activity determines atherosclerotic plaque stability in patients with stable coronary artery disease, In: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY66(15)pp. B124-B124
SB Astley, RM Elliott (2004)The European Nutrigenomics Organisation - Linking genomics, nutrition and health research, In: Nutrition Bulletin29(3)pp. 254-261

We are exposed to a complex mixture of food compounds in the womb and eat a composite mixture of foods throughout life. Our taste changes as we grow and mature, and we become influenced by external factors such as holidays and advertising by the food industry. Intricate biochemical processes extract energy and other useful components, enabling us to grow and live and keep our bodies and minds functioning effectively. There are, however, many food compounds that have biological effects within our bodies, and diet and disease are intimately associated. To address the fractured nature of nutrigenomic research, leading centres in nutritional research from across Europe have put together a Network of Excellence, the European Nutrigenomics Organisation (NuGO): linking genomics, nutrition and health research. Led by Dr Ben van Ommen of the Dutch Centre for Human Nutrigenomics, NuGO has been awarded €17.3 million over a period of 6 years. The project has been over a year, in preparation and currently has 22 partners from 10 EU member states. © 2004 British Nutrition Foundation.

Eleanor Healing, Lisiane Meira, Philip Aston, M.J. Tindall, Ruan Elliott (2016)Measurement of DNA repair activity in hepatocytes exposed to fatty acids, In: Proceedings of the Nutrition Society Volume 75, Issue OCE3 (Summer Meeting, 11–14 July 2016, New technology in nutrition research and practice)75(OCE3)

DNA repair capacity varies greatly between individuals, and evidence has begun to link this variation to cancer risk, obesity and related chronic diseases. There is also emerging evidence that dietary components can affect DNA repair, but research to date has been restricted by methods for measuring DNA repair. This study made use of newly developed microplate-based assays for the direct determination of DNA repair enzyme activities. Lipid loading of the HepG2 human hepatocellular carcinoma cell line was employed as a model to test the hypothesis that hepatic steatosis affects DNA repair activity via induction of oxidative stress.

GM Wortley, RM Elliott, LJ Harvey, SJ Fairweath-Tait (2006)Copper homeostasis: use of in vitro cell systems and transcriptional analysis to detect markers of copper regulation in human subjects., In: PROCEEDINGS OF THE NUTRITION SOCIETY65pp. 103A-103A CAMBRIDGE UNIV PRESS
SB Astley, RM Elliott (2005)How strong is the evidence that lycopene supplementation can modify biomarkers of oxidative damage and DNA repair in human lymphocytes?, In: JOURNAL OF NUTRITION135(8)pp. 2071S-2073S AMER SOCIETY NUTRITIONAL SCIENCE
RM Elliott (2005)Genes, genomes and molecular biology in nutrition research: A story of opportunities and challenges, In: Current Topics in Nutraceutical Research3(3)pp. 189-192

The wealth of freely available genetic information derived from genome mapping projects and the development of functional genomic and other powerful molecular biological tools have lead to profound changes in the scope of life science research and the way it is performed. As in many other disciplines, scientists in the fields of food science and nutrition are now beginning to fully realise the enormous potential these new resources and are seeking to integrate them into their research. However, there are still a number of issues specific to nutrition research that need to be addressed to ensure that this opportunity is exploited to the full. Copyright © 2005 by New Century Health Publishers, LLC.

PJ Schieldrop, RW Gelling, RM Elliott, J Hewitt, TJ Kieffer, CH McIntosh, RA Pederson (1996)Isolation of a murine glucose-dependent insulinotropic polypeptide (GIP) cDNA from a tumor cell line (STC6-14) and quantification of glucose-induced increases in GIP mRNA, In: Biochimica et Biophysica Acta -Gene Structure and Expression1308(2)pp. 111-113
SJ Heaton, JJ Eady, SJ Fairweather-Tait, HJ MCardle, KS Srai, RM Elliott (2007)BeWo cells as an in vitro model for iron transport across the placenta, In: PROCEEDINGS OF THE NUTRITION SOCIETY66pp. 17A-17A CAMBRIDGE UNIV PRESS
R Elliott, S Astley, S Southon, D Archer (2000)The development of DNA repair assays which show that dietary carrots stimulate DNA repair activity, In: IT Johnson, GR Fenwick (eds.), DIETARY ANTICARCINOGENS AND ANTIMUTAGENS(255)pp. 125-128
S Astley, R Elliott, D Archer, S Southon (2000)DNA damage and repair: Relative responses to antioxidant nutrients in the diet, In: IT Johnson, GR Fenwick (eds.), DIETARY ANTICARCINOGENS AND ANTIMUTAGENS(255)pp. 138-142