Metabolomics
Introduction
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Dr David SumptonHead of Metabolomics Facility |
The Metabolomics facility employs state-of-the-art mass spectrometry techniques to measure small molecule (metabolite) changes in cancer cells, to support cancer metabolism research projects within the Institute.
Using high-resolution Thermo Scientific Q-Exactive mass spectrometers and HILIC chromatography, we have well-established LC-MS methods for both targeted and untargeted analysis of small polar molecules. With our targeted approach to metabolomics, we measure approximately 100 metabolites per sample, encompassing a broad range of metabolites of different classes. Experiments using stable isotope tracers (often 13C glucose) enable us to examine the intracellular kinetics of many metabolites produced from the tracer. Using an untargeted approach, metabolomics is used to look for novel metabolic changes, by identifying compounds showing altered abundances in cancer cells.
Our Thermo Scientific Altis triple quad mass spectrometer is used for specific targeted LC-MS/MS analysis, such as the measurement of lysophosphatidic acids. Our LC-MS systems are complemented with our Agilent Technologies GC-MS/MS triple quad instrument, for measuring compounds such as fatty acids and acetate.
We provide advice for sample preparation for a range of sample types, including cell extracts, plasma, urine and tumour tissue, and support for data analysis, based on Thermo Scientific TraceFinder and Compound Discoverer software.
Recent Publications
2024
Ackermann T, Shokry E, Deshmukh R, Anand J, Galbraith LCA, Mitchell L, Rodriguez-Blanco G, Villar VH, Sterken BA, Nixon C, Zanivan S, Blyth K, Sumpton D, Tardito S. Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis. EMBO Mol Med. 2024.
Benzarti M, Neises L, Oudin A, Krötz C, Viry E, Gargiulo E, Pulido C, Schmoetten M, Pozdeev V, Lorenz NI, Ronellenfitsch MW, Sumpton D, Warmoes M, Jaeger C, Lesur A, Becker B, Moussay E, Paggetti J, Niclou SP, Letellier E, Meiser J. PKM2 diverts glycolytic flux in dependence on mitochondrial one-carbon cycle. Cell Rep. 2024;43(3):113868.
Eberhart T, Stanley FU, Ricci L, Chirico T, Ferrarese R, Sisti S, Scagliola A, Baj A, Badurek S, Sommer A, Culp-Hill R, Dzieciatkowska M, Shokry E, Sumpton D, D'Alessandro A, Clementi N, Mancini N, Cardaci S. ACOD1 deficiency offers protection in a mouse model of diet-induced obesity by maintaining a healthy gut microbiota. Cell Death Dis. 2024;15(2):105.
Gounis M, Campos AV, Shokry E, Mitchell L, Dornier E, Rooney N, Dhayade S, Pardo L, Moore M, Novo D, Mowat J, Jamieson C, Kay E, Zanivan S, Nixon C, Macpherson I, Tardito S, Sumpton D, Blyth K, Norman JC, Clarke CJ. Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments. bioRxiv. 2024:2024.2005.2012.593552.
Jans M, Kolata M, Blancke G, D'Hondt A, Gräf C, Ciers M, Sze M, Thiran A, Petta I, Andries V, Verbandt S, Shokry E, Sumpton D, Vande Voorde J, Berx G, Tejpar S, van Loo G, Iliev ID, Remaut H, Vereecke L. Colibactin-driven colon cancer requires adhesin-mediated epithelial binding. Nature. 2024.
Khalaf A, de Beauchamp L, Kalkman E, Rattigan K, Himonas E, Jones J, James D, Shokry ESA, Scott MT, Dunn K, Tardito S, Copland M, Sumpton D, Shanks E, Helgason GV. Nutrient-sensitizing drug repurposing screen identifies lomerizine as a mitochondrial metabolism inhibitor of chronic myeloid leukemia. Sci Transl Med. 2024;16(751):eadi5336.
Kiourtis C, Terradas-Terradas M, Gee LM, May S, Georgakopoulou A, Collins AL, O’Sullivan ED, Baird DP, Hassan M, Shaw R, Tan EH, Müller M, Engelmann C, Andreola F, Hsieh Y-C, Reed LH, Borthwick LA, Nixon C, Clark W, Hanson PS, Sumpton D, Mackay G, Suzuki T, Najumudeen AK, Inman GJ, Campbell A, Barry ST, Quaglia A, Morris CM, LeBeau FEN, Sansom OJ, Kirschner K, Jalan R, Oakley F, Bird TG. Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ. Nature Cell Biology. 2024.
Mahmood M, Liu EM, Shergold AL, Tolla E, Tait-Mulder J, Huerta-Uribe A, Shokry E, Young AL, Lilla S, Kim M, Park T, Boscenco S, Manchon JL, Rodríguez-Antona C, Walters RC, Springett RJ, Blaza JN, Mitchell L, Blyth K, Zanivan S, Sumpton D, Roberts EW, Reznik E, Gammage PA. Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma. Nat Cancer. 2024.
Zarou MM, Rattigan KM, Sarnello D, Shokry E, Dawson A, Ianniciello A, Dunn K, Copland M, Sumpton D, Vazquez A, Helgason GV. Inhibition of mitochondrial folate metabolism drives differentiation through mTORC1 mediated purine sensing. Nat Commun. 2024;15(1):1931.
2023
May S, Müller M, Livingstone CR, Skalka GL, Walsh PJ, Nixon C, Hedley A, Shaw R, Clark W, Voorde JV, Officer-Jones L, Ballantyne F, Powley IR, Drake TM, Kiourtis C, Keith A, Rocha AS, Tardito S, Sumpton D, Le Quesne J, Bushell M, Sansom OJ, Bird TG. Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration. J Hepatol. 2023; 78: 1028-1036
Rattigan KM, Zarou MM, Brabcova Z, Prasad B, Zerbst D, Sarnello D, Kalkman ER, Ianniciello A, Scott MT, Dunn K, Shokry E, Sumpton D, Copland M, Tardito S, Vande Voorde J, Mussai F, Cheng P, Helgason GV. Arginine dependency is a therapeutically exploitable vulnerability in chronic myeloid leukaemic stem cells. EMBO Rep. 2023;10.15252/embr.202256279:e56279.
Ricci L, Stanley FU, Eberhart T, Mainini F, Sumpton D, Cardaci S. Pyruvate transamination and NAD biosynthesis enable proliferation of succinate dehydrogenase-deficient cells by supporting aerobic glycolysis. Cell Death Dis. 2023;14:403.
Rushworth LK, Loveridge C, Salji M, MacLeod M, Mui E, Sumpton D, Neilson M, Hedley A, Alexander L, McCartney E, Patel R, Wallace J, Delles C, Jones R, Leung HY. Phase II proof-of-concept study of atorvastatin in castration-resistant prostate cancer. BJU Int. 2023;131:236-243.
Vande Voorde J, Steven RT, Najumudeen AK, Ford CA, Dexter A, Gonzalez-Fernandez A, Nikula CJ, Xiang Y, Ford L, Maneta Stavrakaki S, Gilroy K, Zeiger LB, Pennel K, Hatthakarnkul P, Elia EA, Nasif A, Murta T, Manoli E, Mason S, Gillespie M, Lannagan TRM, Vlahov N, Ridgway RA, Nixon C, Raven A, Mills M, Athineos D, Kanellos G, Nourse C, Gay DM, Hughes M, Burton A, Yan B, Sellers K, Wu V, De Ridder K, Shokry E, Huerta Uribe A, Clark W, Clark G, Kirschner K, Thienpont B, Li VSW, Maddocks ODK, Barry ST, Goodwin RJA, Kinross J, Edwards J, Yuneva MO, Sumpton D, Takats Z, Campbell AD, Bunch J, Sansom OJ. Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target. Nature Metabolism. 2023;10.1038/s42255-023-00857-0.
Villar VH, Allega MF, Deshmukh R, Ackermann T, Nakasone MA, Vande Voorde J, Drake TM, Oetjen J, Bloom A, Nixon C, Müller M, May S, Tan EH, Vereecke L, Jans M, Blancke G, Murphy DJ, Huang DT, Lewis DY, Bird TG, Sansom OJ, Blyth K, Sumpton D, Tardito S. Hepatic glutamine synthetase controls N5-methylglutamine in homeostasis and cancer. Nature Chemical Biology. 2023;19:292-300.
2022
Blomme A, Peter C, Mui E, Rodriguez Blanco G, An N, Mason LM, Jamieson LE, McGregor GH, Lilla S, Ntala C, Patel R, Thiry M, Kung SHY, Leclercq M, Ford CA, Rushworth LK, McGarry DJ, Mason S, Repiscak P, Nixon C, Salji MJ, Markert E, MacKay GM, Kamphorst JJ, Graham D, Faulds K, Fazli L, Gleave ME, Avezov E, Edwards J, Yin H, Sumpton D, Blyth K, Close P, Murphy DJ, Zanivan S, Leung HY. THEM6-mediated reprogramming of lipid metabolism supports treatment resistance in prostate cancer. EMBO Molecular Medicine. 2022;14:e14764
Cousins A, Olivares O, Markert E, Manoharan A, Bubnova X, Bresolin S, Degn M, Li Z, Silvestri D, McGregor G, Tumanov S, Sumpton D, Kamphorst JJ, Michie AM, Herzyk P, Valsecchi MG, Yeoh AE, Schmiegelow K, Te Kronnie G, Gottlieb E, Halsey C. Central nervous system involvement in childhood acute lymphoblastic leukemia is linked to upregulation of cholesterol biosynthetic pathways. Leukemia. 2022;36:2903–2907
Kay EJ, Paterson K, Riero-Domingo C, Sumpton D, Däbritz JHM, Tardito S, Boldrini C, Hernandez-Fernaud JR, Athineos D, Dhayade S, Stepanova E, Gjerga E, Neilson LJ, Lilla S, Hedley A, Koulouras G, McGregor G, Jamieson C, Johson RM, Park M, Kirschner K, Miller C, Kamphorst JJ, Loayza-Puch F, Saez-Rodriguez J, Mazzone M, Blyth K, Zagoni M, Zanivan S. Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. Nature Metabolism. 2022;4(6):693-710.
Patel R, Ford CA, Rodgers L, Rushworth LK, Fleming J, Mui E, Zhang T, Watson D, Lynch V, Mackay G, Sumpton D, Sansom OJ, Vande Voorde J, Leung HY. Cyclocreatine suppresses creatine metabolism and impairs prostate cancer progression. Cancer Res. 2022;82: 2565–2575.
Salji MJ, Blomme A, Däbritz JHM, Repiscak P, Lilla S, Patel R, Sumpton D, van den Broek NJF, Daly R, Zanivan S, Leung HY. Multi-omics & pathway analysis identify potential roles for tumor N-acetyl aspartate accumulation in murine models of castration-resistant prostate cancer. iScience. 2022;25:104056.
Taurino G, Deshmukh R, Villar VH, Chiu M, Shaw R, Hedley A, Shokry E, Sumpton D, Dander E, D'Amico G, Bussolati O, Tardito S. Mesenchymal stromal cells cultured in physiological conditions sustain citrate secretion with glutamate anaplerosis. Mol Metab. 2022:101532
2021
Ahmed SF, Buetow L, Gabrielsen M, Lilla S, Sibbet GJ, Sumpton D, Zanivan S, Hedley A, Clark W, Huang DT. E3 ligase-inactivation rewires CBL interactome to elicit oncogenesis by hijacking RTK-CBL-CIN85 axis. Oncogene. 2021;40:2149-2164.
Cano-Galiano A, Oudin A, Fack F, Allega MF, Sumpton D, Martinez-Garcia E, Dittmar G, Hau AC, De Falco A, Herold-Mende C, Bjerkvig R, Meiser J, Tardito S, Niclou SP. Cystathionine-γ-lyase drives antioxidant defense in cysteine-restricted IDH1-mutant astrocytomas. Neurooncol Adv. 2021;3:vdab057.
Galbraith LCA, Mui E, Nixon C, Hedley A, Strachan D, MacKay G, Sumpton D, Sansom OJ, Leung HY, Ahmad I. PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer. Oncogene. 2021;40:2355-2366.
Grosso S, Marini A, Gyuraszova K, Voorde JV, Sfakianos A, Garland GD, Tenor AR, Mordue R, Chernova T, Morone N, Sereno M, Smith CP, Officer L, Farahmand P, Rooney C, Sumpton D, Das M, Teodósio A, Ficken C, Martin MG, Spriggs RV, Sun XM, Bushell M, Sansom OJ, Murphy D, MacFarlane M, Le Quesne JPC, Willis AE. The pathogenesis of mesothelioma is driven by a dysregulated translatome. Nat Commun. 2021;12:4920.
Martinez RS, Salji MJ, Rushworth L, Ntala C, Rodriguez Blanco G, Hedley A, Clark W, Peixoto P, Hervouet E, Renaude E, Kung SHY, Galbraith LCA, Nixon C, Lilla S, Mackay GM, Fazli L, Gaughan L, Sumpton D, Gleave ME, Zanivan S, Blomme A, Leung HY. SLFN5 regulates LAT1-mediated mTOR activation in castration-resistant prostate cancer. Cancer Res. 2021;8:3664–3678
Najumudeen AK, Ceteci F, Fey SK, Hamm G, Steven RT, Hall H, Nikula CJ, Dexter A, Murta T, Race AM, Sumpton D, Vlahov N, Gay DM, Knight JRP, Jackstadt R, Leach JDG, Ridgway RA, Johnson ER, Nixon C, Hedley A, et al. The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nat Genet. 2021;53:16-26.
2020
Bellier J, Nokin M-J, Caprasse M, Tiamiou A, Blomme A, Scheijen JL, Koopmansch B, MacKay GM, Chiavarina B, Costanza B, Rademaker G, Durieux F, Agirman F, Maloujahmoum N, Cusumano PG, Lovinfosse P, Leung HY, Lambert F, Bours V, Schalkwijk CG, Hustinx R, Peulen O, Castronovo V, Bellahcène A. Methylglyoxal Scavengers Resensitize KRAS-Mutated Colorectal Tumors to Cetuximab. Cell reports. 2020;30:1400-1416.e1406.
Blomme A, Ford CA, Mui E, Patel R, Ntala C, Jamieson LE, Planque M, McGregor GH, Peixoto P, Hervouet E, Nixon C, Salji M, Gaughan L, Markert E, Repiscak P, Sumpton D, Rodriguez Blanco G, Lilla S, Kamphorst JJ, Graham D, Faulds K, MacKay GM, Fendt S-M, Zanivan S, Leung HY. 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. Nat Commun. 2020; 11: 2508
Braga M, Kaliszczak M, Carroll L, Schug ZT, Heinzmann K, Baxan N, Benito A, Valbuena GN, Stribbling S, Beckley A, Mackay G, Mauri F, Latigo J, Barnes C, Keun H, Gottlieb E, Aboagye EO. Tracing Nutrient Flux Following Monocarboxylate Transporter-1 Inhibition with AZD3965. Cancers (Basel). 2020;12:2181
Chatrin C, Gabrielsen M, Buetow L, Nakasone MA, Ahmed SF, Sumpton D, Sibbet GJ, Smith BO, Huang DT. Structural insights into ADP-ribosylation of ubiquitin by Deltex family E3 ubiquitin ligases. Sci Adv. 2020;6: eabc0418
Dhayade S, Pietzke M, Wiesheu R, Tait-Mulder J, Athineos D, Sumpton D, Coffelt S, Blyth K, Vazquez A. Impact of Formate Supplementation on Body Weight and Plasma Amino Acids. Nutrients. 2020; 12(8):2181.
McGregor GH, Campbell AD, Fey SK, Tumanov S, Sumpton D, Rodriguez Blanco G, Mackay G, Nixon C, Vazquez A, Sansom OJ, Kamphorst JJ. Targeting the metabolic response to statin-mediated oxidative stress produces a synergistic anti-tumor response. Cancer research.
Oizel K, Tait-Mulder J, Fernandez-de-Cossio-Diaz J, Pietzke M, Brunton H, Lilla S, Dhayade S, Athineos D, Blanco GR, Sumpton D, Mackay GM, Blyth K, Zanivan SR, Meiser J, Vazquez A. Formate induces a metabolic switch in nucleotide and energy metabolism. Cell death & disease. 2020;11:310.
Patel R, Brzezinska EA, Repiscak P, Ahmad I, Mui E, Gao M, Blomme A, Harle V, Tan EH, Malviya G, Mrowinska A, Loveridge CJ, Rushworth LK, Edwards J, Ntala C, Nixon C, Hedley A, Mackay G, Tardito S, Sansom OJ, Leung HY. Activation of beta-catenin cooperates with loss of Pten to drive AR-independent castration-resistant prostate cancer. Cancer research.
2019
Juin A, Spence HJ, Martin KJ, McGhee E, Neilson M, Cutiongco MFA, Gadegaard N, Mackay G, Fort L, Lilla S, Kalna G, Thomason P, Koh YWH, Norman JC, Insall RH, Machesky LM. N-WASP Control of LPAR1 Trafficking Establishes Response to Self-Generated LPA Gradients to Promote Pancreatic Cancer Cell Metastasis. Developmental cell. 2019;51: 431 - 445.e7.
Pietzke M, Arroyo SF, Sumpton D, Mackay GM, Martin-Castillo B, Camps J, Joven J, Menendez JA, Vazquez A. Stratification of cancer and diabetes based on circulating levels of formate and glucose. Cancer & metabolism. 2019;7:3.
Shehata SN, Deak M, Collodet C, Spiegl SF, Geley S, Sumpton D, Sakamoto K. Identification of novel PCTAIRE-1/CDK16 substrates using a chemical genetic screen. Cell Signal. 2019; 59: 53-61.
Vande Voorde J, Ackermann T, Pfetzer N, Sumpton D, Mackay G, Kalna G, Nixon C, Blyth K, Gottlieb E, Tardito S. Improving the metabolic fidelity of cancer models with a physiological cell culture medium. Science Advances 2019; 5: eaau7314.
2018
Gonzalez PS, O'Prey J, Cardaci S, Barthet VJA, Sakamaki JI, Beaumatin F, Roseweir A, Gay DM, Mackay G, Malviya G, Kania E, Ritchie S, Baudot AD, Zunino B, Mrowinska A, et al. Mannose impairs tumour growth and enhances chemotherapy. Nature. 2018; 563: 719-23.
Meiser J, Schuster A, Pietzke M, Vande Voorde J, Athineos D, Oizel K, Burgos-Barragan G, Wit N, Dhayade S, Morton JP, Dornier E, Sumpton D, Mackay GM, Blyth K, Patel KJ, et al. Increased formate overflow is a hallmark of oxidative cancer. Nat Commun 2018;9(1):1368.
Patel R, Fleming J, Mui E, Loveridge C, Repiscak P, Blomme A, Harle V, Salji M, Ahmad I, Teo K, Hamdy FC, Hedley A, van den Broek N, Mackay G, Edwards J, et al. Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1. EMBO Mol Med 2018; 10: e8347.
Rath N, Munro J, Cutiongco MF, Jagiello A, Gadegaard N, McGarry L, Unbekandt M, Michalopoulou E, Kamphorst JJ, Sumpton D, Mackay G, Vennin C, Pajic M, Timpson P, Olson MF. Rho Kinase Inhibition by AT13148 Blocks Pancreatic Ductal Adenocarinoma Invasion and Tumor Growth. Cancer Res 2018; 78: 3321-36.
2017
Bulusu V, Tumanov S, Michalopoulou E, van den Broek NJ, MacKay G, Nixon C, Dhayade S, Schug ZT, Vande Voorde J, Blyth K, Gottlieb E, Vazquez A, Kamphorst JJ. Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. Cell Rep 2017; 18: 647–58
Dolfi SC, Medina DJ, Kareddula A, Paratala B, Rose A, Dhami J, Chen S, Ganesan S, Mackay G, Vazquez A, Hirshfield KM. Riluzole exerts distinct antitumor effects from a metabotropic glutamate receptor 1-specific inhibitor on breast cancer cells. Oncotarget 2017; 8: 44639–53
Dornier E, Rabas N, Mitchell L, Novo D, Dhayade S, Marco S, Mackay G, Sumpton D, Pallares M, Nixon C, Blyth K, MacPherson I, Rainero E, Norman JC. Glutaminolysis drives membrane trafficking to promote cancer invasion. Nat Comms 2017; 8: 2255
Maddocks ODK, Athineos D, Cheung EC, Lee P, Zhang T, van den Broek NJF, Mackay GM, Labuschagne CF, Gay D, Kruiswijk F, Blagih J, Vincent DF, Campbell KJ, Ceteci F, Sansom OJ, Blyth K, Vousden KH. Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature 2017; 544: 372-6
Susanto O, Koh YWH, Morrice N, Tumanov S, Thomason PA, Nielson M, Tweedy L, Muinonen-Martin AJ, Kamphorst JJ, Mackay GM, Insall RH. LPP3 mediates self-generation of chemotactic LPA gradients by melanoma cells. J Cell Sci 2017; 130: 3455–66
2016
Meiser J, Tumanov S, Maddocks O, Labuschagne CF, Athineos D, Van Den Broek N, Mackay GM, Gottlieb E, Blyth K, Vousden K, Kamphorst JJ, Vazquez A. Serine one-carbon catabolism with formate overflow. Science Advances. 2016; 2: e1601273
Tweedy L, Knecht DA, Mackay GM, Insall RH. Self-Generated Chemoattractant Gradients: Attractant Depletion Extends the Range and Robustness of Chemotaxis. PLoS Biol. 2016 Mar 16;14(3):e1002404
