Mass Spectrometry
Introduction
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Dr David SumptonHead of Mass Spectometry |
The CRUK Scotland Institute has a well-established expertise in mass spectrometry (MS). We host a broad range of MS instruments supporting a diverse range of research questions and applications. Historically focus has centred around proteomics, the large-scale study of proteins and metabolomics, the study of small molecules or metabolites using MS. More recently, research on the important role lipids play in cancer biology, has been supported using our lipidomics platform.
The facilities core aim is to assist the institute’s scientists with their most challenging analytical questions. Our team is dedicated to developing and applying new methodologies to meet these challenges. Over the years, we have developed numerous analysis pipelines, from studying single proteins along with their interaction partners, to complete proteomes. We have dedicated methods to study post-translational modifications of proteins, such as phosphorylation, ubiquitination, acetylation and oxidation with site localisation. We can measure many classes of metabolites in a targeted fashion. Often, developing methods in collaboration with the institute’s researchers to detect project specific metabolites for the first time. We can also discover novel metabolites using untargeted metabolomics as exemplified in our discovery of N5-methyl-glutamine as a biomarker for β-catenin-driven hepatocellular carcinoma. We are also well experienced in the use of stable isotope tracers to interrogate changes in intracellular kinetics and carbon sources.
Our extensive arsenal has been effectively applied across the full range of preclinical models and clinical samples available at the institute. We provide researchers with scientific support throughout the entire research process, from experimental design to execution, sample processing, data interpretation, and assist with presentations, manuscript preparation and deposition of data in public repositories. We also offer advice and training to users wishing to carry out their own sample preparation, covering a wide range of sample types, including cells, tissues, and biofluids such as plasma, cerebrospinal fluid, urine and stool. Researchers can also be trained in data analysis approaches or are fully supported especially with more complex analysis needs.
This year, we are excited to be adding a new MS imaging platform to the facility and are looking forward to developing approaches to determine the spatial distribution of molecules within tissue. This cutting-edge instrument will provide the means to uncover novel biological insights and offer a fundamentally new way to interrogate changes in the tumour microenvironment and cancer biology.
Recent Publications
2025
Luo X, Kugeratski FG, Dowlatshahi DP, Sugimoto H, Arian KA, Fan Y, Huang L, Wills D, Lilla S, Hodge K, Zanivan SR, LeBleu VS, McAndrews KM, Kalluri R. Engineered Immunomodulatory Extracellular Vesicles from Epithelial Cells with the Capacity for Stimulation of Innate and Adaptive Immunity in Cancer and Autoimmunity. ACS Nano. 2025.
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.
Dawson A, Zarou MM, Prasad B, Bittencourt-Silvestre J, Zerbst D, Himonas E, Hsieh YC, van Loon I, Blanco GR, Ianniciello A, Kerekes Z, Krishnan V, Agarwal P, Almasoudi H, McCluskey L, Hopcroft LEM, Scott MT, Baquero P, Dunn K, Vetrie D, Copland M, Bhatia R, Coffelt SB, Tiong OS, Wheadon H, Zanivan S, Kirschner K, Helgason GV. Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche. Nat Commun. 2024;15(1):1090.
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.
Sanchez-Lopez I, Orantos-Aguilera Y, Pozo-Guisado E, Alvarez-Barientos A, Lilla S, Zanivan S, Lachaud C, Martin-Romero FJ. STIM1 translocation to the nucleus protects cells from DNA damage. Nucleic Acids Res. 2024.
Santi A, Kay EJ, Neilson LJ, McGarry L, Lilla S, Mullin M, Paul NR, Fercoq F, Koulouras G, Rodriguez Blanco G, Athineos D, Mason S, Hughes M, Thomson G, Kieffer Y, Nixon C, Blyth K, Mechta-Grigoriou F, Carlin LM, Zanivan S. Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Sci Signal. 2024;17(827):eade0580.
Singh SP, Smyth DJ, Cunningham KT, Mukundan A, Byeon CH, Hinck CS, White MPJ, Ciancia C, Wąsowska N, Sanders A, Jin R, White RF, Lilla S, Zanivan S, Schoenherr C, Inman GJ, van Dinther M, Ten Dijke P, Hinck AP, Maizels RM. The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Rep. 2024.
Vringer E, Heilig R, Riley JS, Black A, Cloix C, Skalka G, Montes-Gómez AE, Aguado A, Lilla S, Walczak H, Gyrd-Hansen M, Murphy DJ, Huang DT, Zanivan S, Tait SW. Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO J. 2024.
Whitelaw JA, Lilla S, Nikolaou S, Tweedy L, Fort L, Paul NR, Zanivan S, Gadegaard N, Insall RH, Machesky LM. CYRI-B loss promotes enlarged mature focal adhesions and restricts microtubule and ERC1 access to the cell leading edge. bioRxiv. 2024:2024.2003.2026.586838.
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
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. Paracrine secretion of MUFAs prevents ferroptosis in triple-negative breast cancer and reveals selenocysteine synthesis dependency for lung metastasis. bioRxiv. 2023;Volume:2023.2006.2013.544588.
Altea-Manzano P, Doglioni G, Liu Y, Cuadros AM, Nolan E, Fernández-García J, Wu Q, Planque M, Laue KJ, Cidre-Aranaz F, Liu XZ, Marin-Bejar O, Van Elsen J, Vermeire I, Broekaert D, Demeyer S, Spotbeen X, Idkowiak J, Montagne A, Demicco M, Alkan HF, Rabas N, Riera-Domingo C, Richard F, Geukens T, De Schepper M, Leduc S, Hatse S, Lambrechts Y, Kay EJ, Lilla S, Alekseenko A, Geldhof V, Boeckx B, de la Calle Arregui C, Floris G, Swinnen JV, Marine JC, Lambrechts D, Pelechano V, Mazzone M, Zanivan S, Cools J, Wildiers H, Baud V, Grünewald TGP, Ben-David U, Desmedt C, Malanchi I, Fendt SM. A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling. Nat Cancer. 2023; 4: 344–364
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
Mahmood M, Liu EM, Shergold AL, Tolla E, Tait-Mulder J, Uribe AH, Shokry E, Young AL, Lilla S, Kim M, Park T, Manchon JL, Rodriguez-Antona C, Walters RC, Springett RJ, Blaza JN, Zanivan S, Sumpton DA, Roberts EW, Reznik E, Gammage PA. Tumour mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade. bioRxiv. 2023;Volume:2023.2003.2021.533091.
Moore M, Pardo L, Mitchell L, Schmidt T, May S, Mueller M, Strathdee D, Bryson S, Hodge K, Lilla S, Zanivan S, Waldron J, McGarry L, Peter-Durairaj R, Kanellos G, Nixon C, Ballantyne F, LeQuesne J, Sansom OJ, Bird T, Bushell M, Norman JC. The eIF4A2 negative regulator of mRNA translation promotes extracellular matrix deposition to accelerate hepatocellular carcinoma initiation. bioRxiv. 2023;Volume:2023.2008.2016.553544.
Nikolatou K, Sandilands E, Román-Fernández A, Cumming EM, Freckmann E, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant DM. PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer. The EMBO Journal. 2023;n/a:e113987.
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.
Román-Fernández A, Mansour MA, Kugeratski FG, Anand J, Sandilands E, Galbraith L, Rakovic K, Freckmann EC, Cumming EM, Park J, Nikolatou K, Lilla S, Shaw R, Strachan D, Mason S, Patel R, McGarry L, Katoch A, Campbell KJ, Nixon C, Miller CJ, Leung HY, Le Quesne J, Norman JC, Zanivan S, Blyth K, Bryant DM. Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function. Sci Adv. 2023;9:eabq1858.
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.
Santi A, Kay EJ, Neilson LJ, McGarry L, Lilla S, Mullin M, Paul NR, Fercoq F, Koulouras G, Blanco GR, Athineos D, Mason S, Hughes M, Kieffer Y, Nixon C, Blyth K, Mechta-Grigoriou F, Carlin LM, Zanivan S. Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. bioRxiv. 2023;Volume:2023.2001.2013.523951.
Schmidt T, Dabrowska A, Waldron JA, Hodge K, Koulouras G, Gabrielsen M, Munro J, Tack DC, Harris G, McGhee E, Scott D, Carlin Leo M, Huang D, Le Quesne J, Zanivan S, Wilczynska A, Bushell M. eIF4A1-dependent mRNAs employ purine-rich 5’UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation. Nucleic Acids Research. 2023; 51: 1859–1879
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
Baudot AD, Wang VM, Leach JD, O'Prey J, Long JS, Paulus-Hock V, Lilla S, Thomson DM, Greenhorn J, Ghaffar F, Nixon C, Helfrich MH, Strathdee D, Pratt J, Marchesi F, Zanivan S, Ryan KM. Glycan degradation promotes macroautophagy. Proc Natl Acad Sci U S A. 2022;119(26):e2111506119.
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
Camargo L, Samji S, Lilla S, Zanivan S, Bulleid N, Hartley R, Delles C, Leiper J, Fuller W, Montezano A, Touyz R. Proteomic Profile of Cysteine Oxidation in Vascular Smooth Muscle Cells in Human Hypertension. Journal of Hypertension. 2022;40:e225-e226.
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.
McGarry DJ, Castino G, Lilla S, Carnet A, Kelly L, Micovic K, Zanivan S, Olson MF. MICAL1 activation by PAK1 mediates actin filament disassembly. Cell Reports. 2022;41.
Närvä E, Taskinen ME, Lilla S, Isomursu A, Pietilä M, Weltner J, Isola J, Sihto H, Joensuu H, Zanivan S, Norman J, Ivaska J. MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels. iScience. 2022;25:104459.
Nikolatou K, Sandilands E, Roman-Fernandez A, Cumming EM, Freckmann EC, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant D. PTEN deficiency exposes a requirement for an ARF GTPase module in integrin-dependent invasion in ovarian cancer. bioRxiv. 2022;Volume:2022.2011.2029.518198.
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.
Schmidt T, Dabrowska A, Waldron JA, Hodge K, Koulouras G, Gabrielsen M, Munro J, Tack DC, Harris G, McGhee E, Scott D, Carlin LM, Huang D, Le Quesne J, Zanivan S, Wilczynska A, Bushell M. Purine-rich RNA sequences in the 5’UTR site-specifically regulate eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation. bioRxiv. 2022;Volume:2022.2008.2008.503179.
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