Imperial College London

DrHectorKeun

Faculty of MedicineDepartment of Surgery & Cancer

Reader in Metabolic Biochemistry
 
 
 
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Contact

 

+44 (0)20 7594 3161h.keun

 
 
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Location

 

officesInstitute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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134 results found

Ebbels TMD, Rodriguez-Martinez A, Dumas ME, Keun HCet al., 2018, CHAPTER 12: Advances in Computational Analysis of Metabolomic NMR Data, New Developments in NMR, Pages: 310-323

© The Royal Society of Chemistry 2018. In this chapter we discuss some of the more recent developments in preprocessing and statistical analysis of NMR spectra in metabolomics. Bayesian methods for analyzing NMR spectra are summarized and we describe one particular approach, BATMAN, in more detail. We consider techniques based on statistical associations, such as correlation spectroscopy (e.g. STOCSY and recent variants), as well as approaches that model the associations as a network and how these change under different biological conditions. The link between metabolism and genotype is explored by looking at metabolic GWAS and related techniques. Finally, we describe the relevance and current status of data standards for NMR metabolomics.

BOOK CHAPTER

Hilmenyuk T, Ruckstuhl CA, Hayoz M, Berchtold C, Nuoffer J-M, Solanki S, Keun HC, Beavis PA, Riether C, Ochsenbein AFet al., 2018, T cell inhibitory mechanisms in a model of aggressive Non-Hodgkin's Lymphoma, ONCOIMMUNOLOGY, Vol: 7, ISSN: 2162-402X

JOURNAL ARTICLE

Kuepfer L, Clayton O, Thiel C, Cordes H, Nudischer R, Blank LM, Baier V, Heymans S, Caiment F, Roth A, Fluri DA, Kelm JM, Castell J, Selevsek N, Schlapbach R, Keun H, Hynes J, Sarkans U, Gmuender H, Herwig R, Niederer S, Schuchhardt J, Segall M, Kleinjans Jet al., 2018, A model-based assay design to reproduce in vivo patterns of acute drug-induced toxicity, ARCHIVES OF TOXICOLOGY, Vol: 92, Pages: 553-555, ISSN: 0340-5761

JOURNAL ARTICLE

Rodrigues RM, Kollipara L, Chaudhari U, Sachinidis A, Zahedi RP, Sickmann A, Kopp-Schneider A, Jiang X, Keun H, Hengstler J, Oorts M, Annaert P, Hoeben E, Gijbels E, De Kock J, Vanhaecke T, Rogiers V, Vinken Met al., 2018, Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures, ARCHIVES OF TOXICOLOGY, Vol: 92, Pages: 1939-1952, ISSN: 0340-5761

JOURNAL ARTICLE

Vermeulen R, Saberi Hosnijeh F, Bodinier B, Portengen L, Liquet B, Garrido-Manriquez J, Lokhorst H, Bergdahl IA, Kyrtopoulos SA, Johansson A-S, Georgiadis P, Melin B, Palli D, Krogh V, Panico S, Sacerdote C, Tumino R, Vineis P, Castagné R, Chadeau-Hyam M, EnviroGenoMarkers Consortium Consortium members, Botsivali M, Chatziioannou A, Valavanis I, Kleinjans JCS, de Kok TMCM, Keun HC, Athersuch TJ, Kelly R, Lenner P, Hallmans G, Stephanou EG, Myridakis A, Kogevinas M, Fazzo L, De Santis M, Comba P, Bendinelli B, Kiviranta H, Rantakokko P, Airaksinen R, Ruokojarvi P, Gilthorpe M, Fleming S, Fleming T, Tu Y-K, Lundh T, Chien K-L, Chen WJ, Lee W-C, Kate Hsiao C, Kuo P-H, Hung H, Liao S-Fet al., 2018, Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma: Univariate and functionally informed multivariate analyses., Int J Cancer

Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01-15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor-2 (FGF-2 p = 7.2 × 10-4 ) and transforming growth factor alpha (TGF-α, p = 6.5 × 10-5 ) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF-2 (p = 7.8 × 10-7 ), TGF-α (p = 4.08 × 10-5 ), fractalkine (p = 1.12 × 10-3 ), monocyte chemotactic protein-3 (p = 1.36 × 10-4 ), macrophage inflammatory protein 1-alpha (p = 4.6 × 10-4 ) and vascular endothelial growth factor (p = 4.23 × 10-5 ). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case-only analyses showed that Granulocyte-macrophage colony stimulating factor levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progress

JOURNAL ARTICLE

Chatziioannou A, Georgiadis P, Hebels DG, Liampa I, Valavanis I, Bergdahl IA, Johansson A, Palli D, Chadeau-Hyam M, Siskos AP, Keun H, Botsivali M, de Kok TMCM, Perez AE, Kleinjans JCS, Vineis P, Kyrtopoulos SAet al., 2017, Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322

JOURNAL ARTICLE

Chaudhari U, Ellis JK, Wagh V, Nemade H, Hescheler J, Keun HC, Sachinidis Aet al., 2017, Metabolite signatures of doxorubicin induced toxicity in human induced pluripotent stem cell-derived cardiomyocytes, AMINO ACIDS, Vol: 49, Pages: 1955-1963, ISSN: 0939-4451

JOURNAL ARTICLE

Georgiadis P, Liampa I, Hebels DG, Krauskopf J, Chatziioannou A, Valavanis I, de Kok TMCM, Kleinjans JCS, Bergdahl IA, Melin B, Spaeth F, Palli D, Vermeulen RCH, Vlaanderen J, Chadeau-Hyam M, Vineis P, Kyrtopoulos SAet al., 2017, Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis, BMC GENOMICS, Vol: 18, ISSN: 1471-2164

JOURNAL ARTICLE

Itkonen HM, Brown M, Urbanucci A, Tredwell G, Lau CH, Barfeld S, Hart C, Guldvik IJ, Takhar M, Heemers HV, Erho N, Bloch K, Davicioni E, Derua R, Waelkens E, Mohler JL, Clarke N, Swinnen JV, Keun HC, Rekvig OP, Mills IGet al., 2017, Lipid degradation promotes prostate cancer cell survival, ONCOTARGET, Vol: 8, Pages: 38264-38275, ISSN: 1949-2553

JOURNAL ARTICLE

Lau C-HE, Tredwell GD, Ellis JK, Lam EW-F, Keun HCet al., 2017, Metabolomic characterisation of the effects of oncogenic PIK3CA transformation in a breast epithelial cell line, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322

JOURNAL ARTICLE

Maitre L, Lau C-HE, Vizcaino E, Robinson O, Casas M, Siskos AP, Want EJ, Athersuch T, Slama R, Vrijheid M, Keun HC, Coen Met al., 2017, Assessment of metabolic phenotypic variability in children's urine using H-1 NMR spectroscopy, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322

JOURNAL ARTICLE

Siskos AP, Jain P, Romisch-Margl W, Bennet M, Achaintre D, Asad Y, Marney L, Richardson L, Koulman A, Griffin JL, Raynaud F, Scalbert A, Adamski J, Prehn C, Keun HCet al., 2017, Interlaboratory Reproducibility of a Targeted Metabolomics Platform for Analysis of Human Serum and Plasma, ANALYTICAL CHEMISTRY, Vol: 89, Pages: 656-665, ISSN: 0003-2700

JOURNAL ARTICLE

Sood D, Johnson N, Jain P, Siskos AP, Bennett M, Gilham C, Busana MC, Peto J, dos-Santos-Silva I, Keun HC, Fletcher Oet al., 2017, CYP3A7*1C allele is associated with reduced levels of 2-hydroxylation pathway oestrogen metabolites, BRITISH JOURNAL OF CANCER, Vol: 116, Pages: 382-388, ISSN: 0007-0920

JOURNAL ARTICLE

Valbuena GN, Tortarolo M, Bendotti C, Cantoni L, Keun HCet al., 2017, Altered Metabolic Profiles Associate with Toxicity in SOD1(G93A) Astrocyte-Neuron Co-Cultures, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322

JOURNAL ARTICLE

Chaudhari U, Nemade H, Wagh V, Gaspar JA, Ellis JK, Srinivasan SP, Spitkovski D, Nguemo F, Louisse J, Bremer S, Hescheler J, Keun HC, Hengstler JG, Sachinidis Aet al., 2016, Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment, ARCHIVES OF TOXICOLOGY, Vol: 90, Pages: 2763-2777, ISSN: 0340-5761

JOURNAL ARTICLE

Fernando RN, Chaudhari U, Escher SE, Hengstler JG, Hescheler J, Jennings P, Keun HC, Kleinjans JCS, Kolde R, Kollipara L, Kopp-Schneider A, Limonciel A, Nemade H, Nguemo F, Peterson H, Prieto P, Rodrigues RM, Sachinidis A, Schaefer C, Sickmann A, Spitkovsky D, Stoeber R, van Breda SGJ, van de Water B, Vivier M, Zahedi RP, Vinken M, Rogiers Vet al., 2016, "Watching the Detectives" report of the general assembly of the EU project DETECTIVE Brussels, 24-25 November 2015, ARCHIVES OF TOXICOLOGY, Vol: 90, Pages: 1529-1539, ISSN: 0340-5761

JOURNAL ARTICLE

Georgiadis P, Hebels DG, Valavanis I, Liampa I, Bergdahl IA, Johansson A, Palli D, Chadeau-Hyam M, Chatziioannou A, Jennen DGJ, Krauskopf J, Jetten MJ, Kleinjans JCS, Vineis P, Kyrtopoulos SAet al., 2016, Omics for prediction of environmental health effects: Blood leukocyte-based cross-omic profiling reliably predicts diseases associated with tobacco smoking, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322

JOURNAL ARTICLE

Koufaris C, Gallage S, Yang T, Lau C-H, Valbuena GN, Keun HCet al., 2016, Suppression of MTHFD2 in MCF-7 Breast Cancer Cells Increases Glycolysis, Dependency on Exogenous Glycine, and Sensitivity to Folate Depletion, JOURNAL OF PROTEOME RESEARCH, Vol: 15, Pages: 2618-2625, ISSN: 1535-3893

JOURNAL ARTICLE

Koufaris C, Valbuena GN, Pomyen Y, Tredwell GD, Nevedomskaya E, Lau C-H, Yang T, Benito A, Ellis JK, Keun HCet al., 2016, Systematic integration of molecular profiles identifies miR-22 as a regulator of lipid and folate metabolism in breast cancer cells., Oncogene, Vol: 35, Pages: 2766-2776

Dysregulated microRNA (miRNA) mediate malignant phenotypes, including metabolic reprogramming. By performing an integrative analysis of miRNA and metabolome data for the NCI-60 cell line panel, we identified an miRNA cluster strongly associated with both c-Myc expression and global metabolic variation. Within this cluster the cancer-associated and cardioprotective miR-22 was shown to repress fatty acid synthesis and elongation in tumour cells by targeting ATP citrate lyase and fatty acid elongase 6, as well as impairing mitochondrial one-carbon metabolism by suppression of methylene tetrahydrofolate dehydrogenase/cyclohydrolase. Across several data sets, expression of these target genes were associated with poorer outcomes in breast cancer patients. Importantly, a beneficial effect of miR-22 on clinical outcomes in breast cancer was shown to depend on the expression levels of the identified target genes, demonstrating the relevance of miRNA/mRNA interactions to disease progression in vivo. Our systematic analysis establishes miR-22 as a novel regulator of tumour cell metabolism, a function that could contribute to the role of this miRNA in cellular differentiation and cancer development. Moreover, we provide a paradigmatic example of effect modification in outcome analysis as a consequence of miRNA-directed gene targeting, a phenomenon that could be exploited to improve patient prognosis and treatment.

JOURNAL ARTICLE

Kyriakides M, Rama N, Sidhu J, Gabra H, Keun HC, El-Bahrawy Met al., 2016, Metabonomic analysis of ovarian tumour cyst fluid by proton nuclear magnetic resonance spectroscopy, ONCOTARGET, Vol: 7, Pages: 7216-7226, ISSN: 1949-2553

JOURNAL ARTICLE

Nevedomskaya E, Perryman R, Solanki S, Syed N, Mayboroda OA, Keun HCet al., 2016, A Systems Oncology Approach Identifies NT5E as a Key Metabolic Regulator in Tumor Cells and Modulator of Platinum Sensitivity, JOURNAL OF PROTEOME RESEARCH, Vol: 15, Pages: 280-290, ISSN: 1535-3893

JOURNAL ARTICLE

Perng W, Oken E, Roumeliotaki T, Sood D, Siskos AP, Chalkiadaki G, Dermitzaki E, Vafeiadi M, Kyrtopoulos S, Kogevinas M, Keun HC, Chatzi Let al., 2016, Leptin, acylcarnitine metabolites and development of adiposity in the Rhea mother-child cohort in Crete, Greece, OBESITY SCIENCE & PRACTICE, Vol: 2, Pages: 471-476, ISSN: 2055-2238

JOURNAL ARTICLE

Perryman R, O'Neill K, Keun H, Syed Net al., 2016, DETERMINING THE ROLE OF NICOTINAMIDE METABOLISM IN CHEMOSENSITIVITY IN GLIOBLASTOMA MULTIFORME, 21st Annual Scientific Meeting and Education Day of the Society-for-Neuro-Oncology, Publisher: OXFORD UNIV PRESS INC, Pages: 36-36, ISSN: 1522-8517

CONFERENCE PAPER

Valbuena GN, Rizzardini M, Cimini S, Siskos AP, Bendotti C, Cantoni L, Keun HCet al., 2016, Metabolomic Analysis Reveals Increased Aerobic Glycolysis and Amino Acid Deficit in a Cellular Model of Amyotrophic Lateral Sclerosis, MOLECULAR NEUROBIOLOGY, Vol: 53, Pages: 2222-2240, ISSN: 0893-7648

JOURNAL ARTICLE

Yogev O, Barker K, Sikka A, Almeida GS, Hallsworth A, Smith LM, Jamin Y, Ruddle R, Koers A, Webber HT, Raynaud FI, Popov S, Jones C, Petrie K, Robinson SP, Keun HC, Chesler Let al., 2016, p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance, CANCER RESEARCH, Vol: 76, Pages: 3025-3035, ISSN: 0008-5472

JOURNAL ARTICLE

Athersuch TJ, Keun HC, 2015, Metabolic profiling in human exposome studies, MUTAGENESIS, Vol: 30, Pages: 755-762, ISSN: 0267-8357

JOURNAL ARTICLE

Fletcher ME, Boshier PR, Wakabayashi K, Keun HC, Smolenski RT, Kirkham PA, Adcock IM, Barton PJ, Takata M, Marczin Net al., 2015, Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 308, Pages: L1274-L1285, ISSN: 1040-0605

JOURNAL ARTICLE

Giskeodegard GF, Davies SK, Revell VL, Keun H, Skene DJet al., 2015, Diurnal rhythms in the human urine metabolome during sleep and total sleep deprivation, SCIENTIFIC REPORTS, Vol: 5, ISSN: 2045-2322

JOURNAL ARTICLE

Hendrickx DM, Aerts HJWL, Caiment F, Clark D, Ebbels TMD, Evelo CT, Gmuender H, Hebels DGAJ, Herwig R, Hescheler J, Jennen DGJ, Jetten MJA, Kanterakis S, Keun HC, Matser V, Overington JP, Pilicheva E, Sarkans U, Segura-Lepe MP, Sotiriadou I, Wittenberger T, Wittwehr C, Zanzi A, Kleinjans JCSet al., 2015, diXa: a data infrastructure for chemical safety assessment, BIOINFORMATICS, Vol: 31, Pages: 1505-1507, ISSN: 1367-4803

JOURNAL ARTICLE

Miller JA, Pappan K, Thompson PA, Want EJ, Siskos AP, Keun HC, Wulff J, Hu C, Lang JE, Chow H-HSet al., 2015, Plasma Metabolomic Profiles of Breast Cancer Patients after Short-term Limonene Intervention, CANCER PREVENTION RESEARCH, Vol: 8, ISSN: 1940-6207

JOURNAL ARTICLE

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