Imperial College London

ProfessorHectorKeun

Faculty of MedicineDepartment of Surgery & Cancer

Professor of 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
to

145 results found

Parzych K, Saavedra-GarcĂ­a P, Valbuena GN, Al-Sadah HA, Robinson ME, Penfold L, Kuzeva DM, Ruiz-Tellez A, Loaiza S, Holzmann V, Caputo V, Johnson DC, Kaiser MF, Karadimitris A, Lam EW-F, Chevet E, Feldhahn N, Keun HC, Auner HWet al., 2019, The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation., Oncogene

VCP/p97 regulates numerous cellular functions by mediating protein degradation through its segregase activity. Its key role in governing protein homoeostasis has made VCP/p97 an appealing anticancer drug target. Here, we provide evidence that VCP/p97 acts as a regulator of cellular metabolism. We found that VCP/p97 was tied to multiple metabolic processes on the gene expression level in a diverse range of cancer cell lines and in patient-derived multiple myeloma cells. Cellular VCP/p97 dependency to maintain proteostasis was increased under conditions of glucose and glutamine limitation in a range of cancer cell lines from different tissues. Moreover, glutamine depletion led to increased VCP/p97 expression, whereas VCP/p97 inhibition perturbed metabolic processes and intracellular amino acid turnover. GCN2, an amino acid-sensing kinase, attenuated stress signalling and cell death triggered by VCP/p97 inhibition and nutrient shortages and modulated ERK activation, autophagy, and glycolytic metabolite turnover. Together, our data point to an interconnected role of VCP/p97 and GCN2 in maintaining cancer cell metabolic and protein homoeostasis.

JOURNAL ARTICLE

Limonciel A, van Breda SG, Jiang X, Tredwell GD, Wilmes A, Aschauer L, Siskos AP, Sachinidis A, Keun HC, Kopp-Schneider A, de Kok TM, Kleinjans JCS, Jennings Pet al., 2018, Persistence of Epigenomic Effects After Recovery From Repeated Treatment With Two Nephrocarcinogens, FRONTIERS IN GENETICS, Vol: 9, ISSN: 1664-8021

JOURNAL ARTICLE

Haug LS, Sakhi AK, Cequier E, Casas M, Maitre L, Basagana X, Andrusaityte S, Chalkiadaki G, Chatzi L, Coen M, de Bont J, Dedele A, Ferrand J, Grazuleviciene R, Ramon Gonzalez J, Gutzkow KB, Keun H, McEachan R, Meltzer HM, Petraviciene I, Robinson O, Saulnier P-J, Slama R, Sunyer J, Urquiza J, Vafeiadi M, Wright J, Vrijheid M, Thomsen Cet al., 2018, In-utero and childhood chemical exposome in six European mother-child cohorts, ENVIRONMENT INTERNATIONAL, Vol: 121, Pages: 751-763, ISSN: 0160-4120

JOURNAL ARTICLE

Maitre L, Robinson O, Martinez D, Toledano MB, Ibarluzea J, Santa Marina L, Sunyer J, Villanueva CM, Keun HC, Vrijheid M, Coen Met al., 2018, Urine Metabolic Signatures of Multiple Environmental Pollutants in Pregnant Women: An Exposome Approach, ENVIRONMENTAL SCIENCE & TECHNOLOGY, Vol: 52, Pages: 13469-13480, ISSN: 0013-936X

JOURNAL ARTICLE

Lau C-HE, Siskos AP, Maitre L, Robinson O, Athersuch TJ, Want EJ, Urquiza J, Casas M, Vafeiadi M, Roumeliotaki T, McEachan RRC, Azad R, Haug LS, Meltzer HM, Andrusaityte S, Petraviciene I, Grazuleviciene R, Thomsen C, Wright J, Slama R, Chatzi L, Vrijheid M, Keun HC, Coen Met al., 2018, Determinants of the urinary and serum metabolome in children from six European populations, BMC MEDICINE, Vol: 16, ISSN: 1741-7015

JOURNAL ARTICLE

Vermeulen R, Hosnijeh FS, 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, Castagne R, Chadeau-Hyam M, 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, Hsiao CK, 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, INTERNATIONAL JOURNAL OF CANCER, Vol: 143, Pages: 1335-1347, ISSN: 0020-7136

JOURNAL ARTICLE

Maitre L, de Bont J, Casas M, Robinson O, Aasvang GM, Agier L, Andrusaityte S, Ballester F, Basagana X, Borras E, Brochot C, Bustamante M, Carracedo A, de Castro M, Dedele A, Donaire-Gonzalez D, Estivill X, Evandt J, Fossati S, Giorgis-Allemand L, Gonzalez JR, Granum B, Grazuleviciene R, Gutzkow KB, Haug LS, Hernandez-Ferrer C, Heude B, Ibarluzea J, Julvez J, Karachaliou M, Keun HC, Krog NH, Lau C-HE, Leventakou V, Lyon-Caen S, Manzano C, Mason D, McEachan R, Meltzer HM, Petraviciene I, Quentin J, Roumeliotaki T, Sabido E, Saulnier P-J, Siskos AP, Siroux V, Sunyer J, Tamayo I, Urquiza J, Vafeiadi M, van Gent D, Vives-Usano M, Waiblinger D, Warembourg C, Chatzi L, Coen M, van den Hazel P, Nieuwenhuijsen MJ, Slama R, Thomsen C, Wright J, Vrijheid Met al., 2018, Human Early Life Exposome (HELIX) study: a European population-based exposome cohort, BMJ OPEN, Vol: 8, ISSN: 2044-6055

JOURNAL ARTICLE

Berger E, Delpierre C, Hosnijeh FS, Kelly-Irving M, Portengen L, Bergdahl IA, Johansson A-S, Krogh V, Palli D, Panico S, Sacerdote C, Tumino R, Kyrtopoulos SA, Vineis P, Chadeau-Hyam M, Vermeulen R, Castagne Ret al., 2018, Association between low-grade inflammation and Breast cancer and B-cell Myeloma and Non-Hodgkin Lymphoma: findings from two prospective cohorts, SCIENTIFIC REPORTS, Vol: 8, ISSN: 2045-2322

JOURNAL ARTICLE

Sborchia M, De Prez EG, Bienfait L, Indra R, Dracinska H, Nortier J, Stiborova M, Keun H, Arlt VMet al., 2018, Toxicogenomics changes induced by the human carcinogen aristolochic acid I in Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice, Publisher: WILEY, Pages: 11-12, ISSN: 2211-5463

CONFERENCE PAPER

Bravo-Santano N, Ellis JK, Mateos LM, Calle Y, Keun HC, Behrends V, Letek Met al., 2018, Intracellular Staphylococcus aureus Modulates Host Central Carbon Metabolism To Activate Autophagy, MSPHERE, Vol: 3, ISSN: 2379-5042

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

, 2018, CHAPTER 13: NMR Spectroscopy of Cell Culture, Tissues, and Other Biofluids, New Developments in NMR, Pages: 324-359

© The Royal Society of Chemistry 2018. NMR spectroscopy can provide a wealth of information on cellular metabolism and is frequently used in metabolomics application that use cultured cells, tissues, and whole organisms. Central to these analyses are the protocols for sample harvest, which incorporate procedures for quenching metabolic processes to preserve samples in a state that is representative of their source. In this chapter, the main considerations are discussed with reference to literature exemplars. In the latter half of the chapter, less commonly studied biofluids that also have specific sample preparation requirements are discussed, with a focus on cerebrospinal fluid, faeces, bile, seminal fluid, and milk.

BOOK CHAPTER

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

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

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

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

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

Sikka A, Barnes EME, Keun HC, 2017, The role of biophysics and engineering in investigating tumour pH and its regulation, CONVERGENT SCIENCE PHYSICAL ONCOLOGY, Vol: 3, ISSN: 2057-1739

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

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

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

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

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

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

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

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