Imperial College London

ProfessorElaineHolmes

Faculty of MedicineDepartment of Surgery & Cancer

Professor of Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 3220elaine.holmes

 
 
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Location

 

661Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

528 results found

Boulangé CL, Rood IM, Posma JM, Lindon JC, Holmes E, Wetzels JFM, Deegens JKJ, Kaluarachchi MRet al., 2019, NMR and MS urinary metabolic phenotyping in kidney diseases is fit-for-purpose in the presence of a protease inhibitor., Mol Omics

Nephrotic syndrome with idiopathic membranous nephropathy as a major contributor, is characterized by proteinuria, hypoalbuminemia and oedema. Diagnosis is based on renal biopsy and the condition is treated using immunosuppressive drugs; however nephrotic syndrome treatment efficacy varies among patients. Multi-omic urine analyses can discover new markers of nephrotic syndrome that can be used to develop personalized treatments. For proteomics, a protease inhibitor (PI) is sometimes added at sample collection to conserve proteins but its impact on urine metabolic phenotyping needs to be evaluated. Urine from controls (n = 4) and idiopathic membranous nephropathy (iMN) patients (n = 6) were collected with and without PI addition and analysed using 1H NMR spectroscopy and UPLC-MS. PI-related data features were observed in the 1H NMR spectra but their removal followed by a median fold change normalisation, eliminated the PI contribution. PI-related metabolites in UPLC-MS data had limited effect on metabolic patterns specific to iMN. When using an appropriate data processing pipeline, PI-containing urine samples are appropriate for 1H NMR and MS metabolic profiling of patients with nephrotic syndrome.

JOURNAL ARTICLE

Mullish BH, McDonald JAK, Pechlivanis A, Allegretti JR, Kao D, Barker GF, Kapila D, Petrof EO, Joyce SA, Gahan CGM, Glegola-Madejska I, Williams HRT, Holmes E, Clarke TB, Thursz MR, Marchesi JRet al., 2019, Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection, Gut, ISSN: 0017-5749

JOURNAL ARTICLE

Adesina-Georgiadis KN, Gray N, Plumb RS, Thompson DF, Holmes E, Nicholson JK, Wilson IDet al., 2018, The Metabolic Fate and Effects of 2-Bromophenol in Male Sprague-Dawley Rats., Xenobiotica, Pages: 1-22

1. The metabolic fate and urinary excretion of 2-bromophenol, a phenolic metabolite of bromobenzene, was investigated in male Sprague Dawley rats following single intraperitoneal doses at either 0, 100 or 200 mg/kg. 2. Urine was collected for seven days and samples analysed using 1H NMR spectroscopy, inductively coupled plasma (ICP)MS, and UPLC-MS. 3. 1H NMR spectroscopy of the urine samples showed that, at these doses, 2-bromophenol had little effect on endogenous metabolite profiles, supporting histopathology and clinical chemistry data which showed no changes associated with the administration of 2-bromophenol at these doses. 4. The use of ICP-MS Provided a means for the selective detection and quantification of bromine-containing species and showed that between 15 and 30% of the dose was excreted via the urine over the 7 days of the study for both the 100 and 200 mg doses respectively. 6. The bulk of the excretion of Br-containing material had occurred by 8 hr post administration. UPLC-MS of urine revealed a number of metabolites of 2-bromophenol, with 2-bromophenol glucuronide and 2-bromophenol sulphate identified as the major species. A number of minor hydroxylated metabolites were also detected as their glucuronide, sulphate or O-methyl conjugates. There was no evidence for the production of reactive metabolites.

JOURNAL ARTICLE

Izzi-Engbeaya C, Comninos AN, Clarke SA, Jomard A, Yang L, Jones S, Abbara A, Narayanaswamy S, Eng PC, Papadopoulou D, Prague JK, Bech P, Godsland IF, Bassett P, Sands C, Camuzeaux S, Gomez-Romero M, Pearce JTM, Lewis MR, Holmes E, Nicholson JK, Tan T, Ratnasabapathy R, Hu M, Carrat G, Piemonti L, Bugliani M, Marchetti P, Johnson PR, Hughes SJ, James Shapiro AM, Rutter GA, Dhillo WSet al., 2018, The effects of kisspeptin on beta-cell function, serum metabolites and appetite in humans, DIABETES OBESITY & METABOLISM, Vol: 20, Pages: 2800-2810, ISSN: 1462-8902

JOURNAL ARTICLE

McDonald JAK, Mullish BH, Pechlivanis A, Liu Z, Brignardello J, Kao D, Holmes E, Li JV, Clarke TB, Thursz MR, Marchesi JRet al., 2018, Inhibiting Growth of Clostridioides difficile by Restoring Valerate, Produced by the Intestinal Microbiota, GASTROENTEROLOGY, Vol: 155, Pages: 1495-+, ISSN: 0016-5085

JOURNAL ARTICLE

Jimenez B, Holmes E, Heude C, Tolson RF, Harvey N, Lodge SL, Chetwynd AJ, Cannet C, Fang F, Pearce JTM, Lewis MR, Viant MR, Lindon JC, Spraul M, Schaefer H, Nicholson JKet al., 2018, Quantitative Lipoprotein Subclass and Low Molecular Weight Metabolite Analysis in Human Serum and Plasma by H-1 NMR Spectroscopy in a Multilaboratory Trial, ANALYTICAL CHEMISTRY, Vol: 90, Pages: 11962-11971, ISSN: 0003-2700

JOURNAL ARTICLE

Antcliffe DB, Wolfer AM, O'Dea KP, Takata M, Holmes E, Gordon ACet al., 2018, Profiling inflammatory markers in patients with pneumonia on intensive care, SCIENTIFIC REPORTS, Vol: 8, ISSN: 2045-2322

JOURNAL ARTICLE

Chekmeneva E, Correia GDS, Gomez-Romero M, Stamler J, Chan Q, Elliott P, Nicholson JK, Holmes Eet al., 2018, Ultra-Performance Liquid Chromatography High-Resolution Mass Spectrometry and Direct Infusion-High-Resolution Mass Spectrometry for Combined Exploratory and Targeted Metabolic Profiling of Human Urine, JOURNAL OF PROTEOME RESEARCH, Vol: 17, Pages: 3492-3502, ISSN: 1535-3893

JOURNAL ARTICLE

Liu Z, Xia B, Saric J, Utzinger J, Holmes E, Keiser J, Li JVet al., 2018, Effects of Vancomycin and Ciprofloxacin on the NMRI Mouse Metabolism, JOURNAL OF PROTEOME RESEARCH, Vol: 17, Pages: 3565-3573, ISSN: 1535-3893

JOURNAL ARTICLE

Abellona MRU, Mark P, Ladep N, Oleribe O, Reeves H, Greer S, Prince M, Ryder SD, Nash K, Cramp ME, Thursz MR, Nicholson J, Taylor-Robinson S, Ndow G, D'Alessandro U, Njie R, Okeke E, Holmes E, Lemoine Met al., 2018, Elucidating Serum and Urinary Hepatocellular Carcinoma Diagnostic Biomarker Panels: Insight from the United Kingdom and West Africa, Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: WILEY, Pages: 37A-38A, ISSN: 0270-9139

CONFERENCE PAPER

Puthucheary ZA, Astin R, Mcphail MJW, Saeed S, Pasha Y, Bear DE, Constantin D, Velloso C, Manning S, Calvert L, Singer M, Batterham RL, Gomez-Romero M, Holmes E, Steiner MC, Atherton PJ, Greenhaff P, Edwards LM, Smith K, Harridge SD, Hart N, Montgomery HEet al., 2018, Metabolic phenotype of skeletal muscle in early critical illness, THORAX, Vol: 73, Pages: 926-935, ISSN: 0040-6376

JOURNAL ARTICLE

Hoyles L, Fernandez-Real J-M, Federici M, Serino M, Abbott J, Charpentier J, Heymes C, Luque JL, Anthony E, Barton RH, Chilloux J, Myridakis A, Martinez-Gili L, Moreno-Navarrete JM, Benhamed F, Azalbert V, Blasco-Baque V, Puig J, Xifra G, Ricart W, Tomlinson C, Woodbridge M, Cardellini M, Davato F, Cardolini I, Porzio O, Gentileschi P, Lopez F, Foufelle F, Butcher SA, Holmes E, Nicholson JK, Postic C, Burcelin R, Dumas M-Eet al., 2018, Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women (vol 24, pg 1070, 2018), NATURE MEDICINE, Vol: 24, Pages: 1628-1628, ISSN: 1078-8956

JOURNAL ARTICLE

Byrne CS, Preston T, Brignardello J, Garcia-Perez I, Holmes E, Frost GS, Morrison DJet al., 2018, The effect of L-rhamnose on intestinal transit time, short chain fatty acids and appetite regulation: a pilot human study using combined (CO2)-C-13/H-2 breath tests, JOURNAL OF BREATH RESEARCH, Vol: 12, ISSN: 1752-7155

JOURNAL ARTICLE

Posma JM, 2018, Multivariate statistical methods for metabolic phenotyping, The Handbook of Metabolic Phenotyping, Editors: Lindon, Holmes, Nicholson, Publisher: Elsevier

The nature of metabolic phenotyping data, where typically more variables are measured than samples are available, requires careful application of statistical methods in order to be able to make meaningful inferences from the data. This Chapter describes different aspects of the multivariate modelling of this type of data, including data transformations and partitioning, unsupervised algorithms for dimension reduction, supervised algorithms for classification, clustering and regression, metrics and methods for obtaining unbiased prediction error estimates of predictive models and statistical spectroscopy tools used for biomarker identification. It focusses on describing methods routinely applied in the field as well as discussing methods that, as computational advancements are made, are poised to become more widely applied to metabolic phenotyping data.

BOOK CHAPTER

Hoyles L, Fernandez-Real J-M, Federici M, Serino M, Abbott J, Charpentier J, Heymes C, Latorre Luque J, Anthony E, Barton RH, Chilloux J, Myridakis A, Martinez-Gili L, Maria Moreno-Navarrete J, Benhamed F, Azalbert V, Blasco-Baque V, Puig J, Xifra G, Ricart W, Tomlinson C, Woodbridge M, Cardellini M, Davato F, Cardolini I, Porzio O, Gentileschi P, Lopez F, Foufelle F, Butcher SA, Holmes E, Nicholson JK, Postic C, Burcelin R, Dumas M-Eet al., 2018, Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women, NATURE MEDICINE, Vol: 24, Pages: 1070-+, ISSN: 1078-8956

JOURNAL ARTICLE

Patiny L, Zasso M, Kostro D, Bernal A, Castillo AM, Bolanos A, Asencio MA, Pellet N, Todd M, Schloerer N, Kuhn S, Holmes E, Javor S, Wist Jet al., 2018, The C6H6 NMR repository: An integral solution to control the flow of your data from the magnet to the public, MAGNETIC RESONANCE IN CHEMISTRY, Vol: 56, Pages: 520-528, ISSN: 0749-1581

JOURNAL ARTICLE

McDonald JAK, Kimhofer T, West K, Coales I, Holmes E, Marchesi J, Nicholson Jet al., Role of the gut microbiota in autism spectrum disorder, ISME17, Publisher: Nature Publishing Group

CONFERENCE PAPER

McDonald JAK, Mullish BH, Pechlivanis A, Liu Z, Brignardello J, Kao D, Holmes E, Li JV, Clarke TB, Thursz MR, Marchesi JRet al., 2018, 0503 - A novel route for controlling Clostridioides difficile growth via bile acid and short chain fatty acid modulation, ISME17

CONFERENCE PAPER

Cronin O, Barton W, Skuse P, Penney NC, Garcia-Perez I, Murphy EF, Woods T, Nugent H, Fanning A, Melgar S, Falvey EC, Holmes E, Cotter PD, O'Sullivan O, Molloy MG, Shanahan Fet al., 2018, A Prospective Metagenomic and Metabolomic Analysis of the Impact of Exercise and/or Whey Protein Supplementation on the Gut Microbiome of Sedentary Adults, MSYSTEMS, Vol: 3, ISSN: 2379-5077

JOURNAL ARTICLE

McDonald JA, Mullish BH, Pechlivanis A, Li JV, Nicholson JK, Holmes E, Thursz MR, Marchesi Jet al., 2018, A NOVEL ROUTE TO CONTROLLING CLOSTRIDIOIDES DIFFICILE GROWTH VIA SHORT CHAIN FATTY ACID AND BILE ACID MODULATION, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S8-S8, ISSN: 0016-5085

CONFERENCE PAPER

Sung Y, Spagou K, Kafeza M, Kyriakides M, Dharmarajah B, Shalhoub J, Diaz JA, Wakefield TW, Holmes E, Davies AHet al., 2018, Deep Vein Thrombosis Exhibits Characteristic Serum and Vein Wall Metabolic Phenotypes in the Inferior Vena Cava Ligation Mouse Model, Annual Meeting of the Society-of-Academic-and-Research-Surgery (SARS), Publisher: W B SAUNDERS CO LTD, Pages: 703-713, ISSN: 1078-5884

CONFERENCE PAPER

Posma JM, Garcia-Perez I, Ebbels TMD, Lindon JC, Stamler J, Elliott P, Holmes E, Nicholson JKet al., 2018, Optimized Phenotypic Biomarker Discovery and Confounder Elimination via Covariate-Adjusted Projection to Latent Structures from Metabolic Spectroscopy Data, JOURNAL OF PROTEOME RESEARCH, Vol: 17, Pages: 1586-1595, ISSN: 1535-3893

JOURNAL ARTICLE

Barton W, Penney NC, Cronin O, Garcia-Perez I, Molloy MG, Holmes E, Shanahan F, Cotter PD, O'Sullivan Oet al., 2018, The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level, GUT, Vol: 67, Pages: 625-633, ISSN: 0017-5749

JOURNAL ARTICLE

Loo RL, Zou X, Appel LJ, Nicholson JK, Holmes Eet al., 2018, Characterization of metabolic responses to healthy diets and association with blood pressure: application to the Optimal Macronutrient Intake Trial for Heart Health (OmniHeart), a randomized controlled study, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 107, Pages: 323-334, ISSN: 0002-9165

JOURNAL ARTICLE

Sung Y, Spagou K, Kafeza M, Kyriakides M, Dharmarajah B, Shalhoub J, Diaz JA, Wakefield T, Holmes E, Davies Aet al., Deep vein thrombosis exhibits characteristic serum and vein wall metabolic phenotypes in the inferior vena cava ligation mouse model, European Journal of Vascular and Endovascular Surgery, ISSN: 1078-5884

Deep vein thrombosis (DVT) is a major health problem, responsible for significant morbidity and mortality, and imposes a heavy economic burden to healthcare systems (1). Although most events resolve without complication through spontaneous lysis and recanalization, DVT can be complicated with life-threatening pulmonary embolism (2), while approximately one third of DVT patients develop post-thrombotic syndrome with swelling, pain, skin changes and/or venous ulceration (3).Treatment with anticoagulation prevents further thrombus extension, protects from pulmonary embolism and reduces the risk of chronic lower limb complications. Importantly, unnecessary treatment can result in bleeding. Therefore, accurate and reliable DVT diagnosis is essential. Currently, diagnosis relies on subjective clinical examination and ultrasound imaging (4). A number of biological markers have been investigated with variable results. D-dimer, the most widely used biomarker, is sensitive but lacks specificity (5, 6). Ongoing research efforts target the utility of alternative blood diagnostic biomarkers able to accurately diagnose DVT, guide length and type of treatment, and potentially identify patients who may benefit from more aggressive therapies than standard anticoagulation. New molecular technologies and methods have entered the scientific arena, offering the opportunity to revisit this important clinical need. Metabolic profiling has emerged as a new approach to investigate complex metabolic disease and enable precision medicine. Metabolomics is the comprehensive and systematic identification of the small molecules present in differential abundance in biofluids and are affected by various factors such as diet, lifestyle, genetics, disease, environmental factors and medications. Metabolic profiling approaches to characterizing the metabolome can be either targeted or untargeted. In targeted approaches specific metabolites, representative of suspected biological pathways, are analysed

JOURNAL ARTICLE

Brown RG, Marchesi JR, Lee YS, Smith A, Lehne B, Kindinger LM, Terzidou V, Holmes E, Nicholson JK, Bennett PR, MacIntyre DAet al., 2018, Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin, BMC MEDICINE, Vol: 16, ISSN: 1741-7015

JOURNAL ARTICLE

Cobbold JFL, Atkinson S, Marchesi JR, Smith A, Wai SN, Stove J, Shojaee-Moradie F, Jackson N, Umpleby AM, Fitzpatrick J, Thomas EL, Bell JD, Holmes E, Taylor-Robinson SD, Goldin RD, Yee MS, Anstee QM, Thursz MRet al., 2018, Rifaximin in non-alcoholic steatohepatitis: An open-label pilot study, HEPATOLOGY RESEARCH, Vol: 48, Pages: 69-77, ISSN: 1386-6346

JOURNAL ARTICLE

Alkandari A, Ashrafian H, Sathyapalan T, Sedman P, Darzi A, Holmes E, Athanasiou T, Atkin SL, Gooderham NJet al., 2018, Improved physiology and metabolic flux after Roux-en-Y gastric bypass is associated with temporal changes in the circulating microRNAome: a longitudinal study in humans., BMC Obes, Vol: 5, ISSN: 2052-9538

Background: The global pandemic of obesity and the metabolic syndrome are leading causes of mortality and morbidity. Bariatric surgery leads to sustained weight loss and improves obesity-associated morbidity including remission of type 2 diabetes. MicroRNAs are small, endogenous RNAs that regulate gene expression post-transcriptionally, controlling most of the human transcriptome and contributing to the regulation of systemic metabolism. This preliminary, longitudinal, repeat sampling study, in which subjects acted as their own control, aimed to assess the temporal effect of bariatric surgery on circulating microRNA expression profiles. Methods: We used Exiqon's optimized circulating microRNA panel (comprising 179 validated miRNAs) and miRCURY locked nucleic acid plasma/serum Polymerase Chain Reaction (PCR) to assess circulating microRNA expression. The microRNAome was determined for Roux-en-Y gastric bypass (RYGB) patients examined preoperatively and at 1 month, 3 months, 6 months, 9 months and 12 months postoperatively. Data was analysed using multivariate and univariate statistics. Results: Compared to the preoperative circulating microRNA expression profile, RYGB altered the circulating microRNAome in a time dependent manner and the expression of 48 circulating microRNAs were significantly different. Importantly, these latter microRNAs are associated with pathways involved in regulation and rescue from metabolic dysfunction and correlated with BMI, the percentage of excess weight loss and fasting blood glucose levels. Conclusions: The results of this pilot study show that RYGB fundamentally alters microRNA expression in circulation with a time-dependent progressive departure in profile from the preoperative baseline and indicate that microRNAs are potentially novel biomarkers for the benefits of bariatric surgery.

JOURNAL ARTICLE

Lamour SD, Alibu VP, Holmes E, Sternberg JMet al., 2017, Metabolic Profiling of Central Nervous System Disease in Trypanosoma brucei rhodesiense Infection, JOURNAL OF INFECTIOUS DISEASES, Vol: 216, Pages: 1273-1280, ISSN: 0022-1899

JOURNAL ARTICLE

Bracewell-Milnes T, Saso S, Abdalla H, Nikolau D, Norman-Taylor J, Johnson M, Holmes E, Thum M-Yet al., 2017, Metabolomics as a tool to identify biomarkers to predict and improve outcomes in reproductive medicine: a systematic review, HUMAN REPRODUCTION UPDATE, Vol: 23, Pages: 723-736, ISSN: 1355-4786

JOURNAL ARTICLE

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