Van Andel Institute

Contact Info:

Ryan Sheldon

333 Bostwick Ave NE

Grand Rapids, MI 49503

https://massspec.vai.org/

Grants and Identifiers:

RRID: RRID:SCR_024903

Instrumentation:

Services Provided:

Lipidomics

Mass Spectrometry

Mass Spectrometry - Proteins And Peptides

Mass Spectrometry - Small Molecules

Metabolomics

Proteomics

Stable Isotope Tracing

Relevant Publications:

1.) Nauta KM, Gates DR, Weiland M, Mechan-Llontop ME, Wang X, Nguyen KP, Isaguirre C, Genjdar MR, Sheldon RD, Krawczyk CM, Burton NO (2025 Jan 23). A noncanonical polyamine from bacteria antagonizes animal mitochondrial function bioRxiv, (), 2024.04.29.591726. . PMCID: 11092615.

2.) Norden PR, Wedan RJ, Longenecker JZ, Preston SEJ, Graber N, Pentecost OA, Canfield M, McLaughlin E, Nowinski SM (2024 Nov 4). Mitochondrial Phosphopantetheinylation is Required for Oxidative Function. bioRxiv : the preprint server for biology, (), . . PMID: 38766035.

3.) Kaluba FC, Rogers TJ, Jeong YJ, Waldhart A, Sokol KH, Lee CJ, Daniels SR, Longo J, Johnson A, Sheldon RD, Jones RG, Lien EC (2024 Nov 3). An alternative route for β-hydroxybutyrate metabolism supports fatty acid synthesis in cancer cells bioRxiv, (), 2024.10.31.621317. . PMCID: 11565918.

4.) Ensing J, Ide AD, Gilliland C, Tsurho V, Caza I, Stratman AN, Lanning NJ, Grainger S (2024 Oct 25). The E3 Ubiquitin Ligase Trip12 attenuates Wnt9a/Fzd9b signaling during hematopoietic stem cell development. bioRxiv : the preprint server for biology, (), . . PMID: 39484584.

5.) Panzeri I, Madaj Z, Fagnocchi L, Apostle S, Tompkins M, Hostetter G, Pospisilik JA (2024 Oct 16). Chronic obesity does not alter cancer survival in Tp53R270H/+ mice bioRxiv, (), 2024.10.14.618190. . PMCID: 11507782.

6.) Panzeri I, Madaj Z, Fagnocchi L, Apostle S, Tompkins M, Hostetter G, Pospisilik JA (2024 Oct 16). Chronic obesity does not alter cancer survival in Tp53 (R270H/+) mice. bioRxiv : the preprint server for biology, (), . . PMID: 39463991.

7.) Longo J, DeCamp LM, Oswald BM, Teis R, Reyes-Oliveras A, Dahabieh MS, Ellis AE, Vincent MP, Damico H, Gallik KL, Compton SE, Capan CD, Williams KS, Esquibel CR, Madaj ZB, Lee H, Roy DG, Krawczyk CM, Haab BB, Sheldon RD, Jones RG (2024 Oct 14). Glucose-dependent glycosphingolipid biosynthesis fuels CD8(+) T cell function and tumor control. bioRxiv : the preprint server for biology, (), . . PMID: 39464161.

8.) House R(, Soper-Hopper MT, Vincent MP, Ellis AE, Capan CD, Madaj ZB, Wolfrum E, Isaguirre CN, Castello CD, Johnson AB, Escobar Galvis ML, Williams KS, Lee H, Sheldon RD (2024 Jul 10). A diverse proteome is present and enzymatically active in metabolite extracts Nature Communications, 15(), 5796. . PMCID: 11237058.

9.) Dahabieh MS, DeCamp LM, Oswald BM, Kitchen-Goosen SM, Fu Z, Vos M, Compton SE, Longo J, Williams KS, Ellis AE, Johnson A, Sodiya I, Vincent M, Lee H, Sheldon RD, Krawczyk CM, Yao C, Wu T, Jones RG (2024 Jun 28). NRF2-dependent regulation of the prostacyclin receptor PTGIR drives CD8 T cell exhaustion bioRxiv, (), 2024.06.23.600279. . PMCID: 11230227.

10.) House RJ, Tovar EA, Essenburg CJ, Dischinger PS, Ellis AE, Beddows I, Sheldon RD, Lien EC, Graveel CR, Steensma MR (2024 Jan 10). NF1 deficiency drives metabolic reprogramming in ER+ breast cancer. Molecular metabolism, (), 101876. doi: 10.1016/j.molmet.2024.101876. ID: 38216123.

11.) Martin KR, Celano SL, Sheldon RD, Jones RG, MacKeigan JP (2023 Dec 3). Quantitative Analysis of Autophagy in Single Cells: Differential Response to Amino Acid and Glucose Starvation. bioRxiv : the preprint server for biology, (), . . ID: 38077042.

12.) Zhao Y, Liu Z, Liu G, Zhang Y, Liu S, Gan D, Chang W, Peng X, Sung ES, Gilbert K, Zhu Y, Wang X, Zeng Z, Baldwin H, Ren G, Weaver J, Huron A, Mayberry T, Wang Q, Wang Y, Diaz-Rubio ME, Su X, Stack MS, Zhang S, Lu X, Sheldon RD, Li J, Zhang C, Wan J, Lu X (2023 Oct 3). Neutrophils resist ferroptosis and promote breast cancer metastasis through aconitate decarboxylase 1. Cell metabolism, 35(10), 1688-1703.e10. . ID: 37793345.

13.) Schofield JH, Longo J, Sheldon RD, Albano E, Hawk MA, Murphy S, Duong L, Rahmy S, Lu X, Jones RG, Schafer ZT (2023 Sep 17). Acod1 Expression in Cancer Cells Promotes Immune Evasion through the Generation of Inhibitory Peptides. bioRxiv : the preprint server for biology, (), . . ID: 37745450.

14.) Luda KM, Longo J, Kitchen-Goosen SM, Duimstra LR, Ma EH, Watson MJ, Oswald BM, Fu Z, Madaj Z, Kupai A, Dickson BM, DeCamp LM, Dahabieh MS, Compton SE, Teis R, Kaymak I, Lau KH, Kelly DP, Puchalska P, Williams KS, Krawczyk CM, Lévesque D, Boisvert FM, Sheldon RD, Rothbart SB, Crawford PA, Jones RG (2023 Sep 12). Ketolysis drives CD8(+) T cell effector function through effects on histone acetylation. Immunity, 56(9), 2021-2035.e8. . ID: 37516105.

15.) Ma EH, Dahabieh MS, DeCamp LM, Kaymak I, Kitchen-Goosen SM, Roy DG, Verway MJ, Johnson RM, Samborska B, Scullion CA, Steadman M, Vos M, Roddy TP, Krawczyk CM, Williams KS, Sheldon RD, Jones RG (2023 Jun 11). (13)C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8(+) T cells. bioRxiv : the preprint server for biology, (), . . ID: 37333111.

16.) Schultz CR, Sheldon RD, Xie H, Demireva EY, Uhl KL, Agnew DW, Geerts D, Bachmann AS (2023 Mar 15). New K50R mutant mouse models reveal impaired hypusination of eif5a2 with alterations in cell metabolite landscape. Biology open, 12(3), . . ID: 36848144.

17.) Madaj ZB, Dahabieh MS, Kamalumpundi V, Muhire B, Pettinga J, Siwicki RA, Ellis AE, Isaguirre C, Escobar Galvis ML, DeCamp L, Jones RG, Givan SA, Adams M, Sheldon RD (2023 Jan). Prior metabolite extraction fully preserves RNAseq quality and enables integrative multi- RNA biology, 20(1), 186-197. . ID: 37095747.

18.) Kilgour MK, MacPherson S, Zacharias LG, LeBlanc J, Babinszky S, Kowalchuk G, Parks S, Sheldon RD, Jones RG, DeBerardinis RJ, Hamilton PT, Watson PH, Lum JJ (2022 Nov). Principles of reproducible metabolite profiling of enriched lymphocytes in tumors and ascites from human ovarian cancer. Nature protocols, 17(11), 2668-2698. doi: 10.1038/s41596-022-00729-z. ID: 35986218.

19.) Guak H, Sheldon RD, Beddows I, Vander Ark A, Weiland MJ, Shen H, Jones RG, St-Pierre J, Ma EH, Krawczyk CM (2022 Sep 26). PGC-1β maintains mitochondrial metabolism and restrains inflammatory gene expression. Scientific reports, 12(1), 16028. . ID: 36163487.

20.) Kaymak I, Luda KM, Duimstra LR, Ma EH, Longo J, Dahabieh MS, Faubert B, Oswald BM, Watson MJ, Kitchen-Goosen SM, DeCamp LM, Compton SE, Fu Z, DeBerardinis RJ, Williams KS, Sheldon RD, Jones RG (2022 Sep 6). Carbon source availability drives nutrient utilization in CD8(+) T cells. Cell metabolism, 34(9), 1298-1311.e6. . ID: 35981545.

21.) Sheldon RD, Ma EH, DeCamp LM, Williams KS, Jones RG (2021 Sep). Interrogating in vivo T-cell metabolism in mice using stable isotope labeling metabolomics and rapid cell sorting. Nature protocols, 16(9), 4494-4521. doi: 10.1038/s41596-021-00586-2. ID: 34349284.

22.) Yan Y, Mukherjee S, Harikumar KG, Strutzenberg TS, Zhou XE, Suino-Powell K, Xu TH, Sheldon RD, Lamp J, Brunzelle JS, Radziwon K, Ellis A, Novick SJ, Vega IE, Jones RG, Miller LJ, Xu HE, Griffin PR, Kossiakoff AA, Melcher K (2021 Jul 23). Structure of an AMPK complex in an inactive, ATP-bound state. Science (New York, N.Y.), 373(6553), 413-419. . ID: 34437114.

23.) Bambouskova M, Potuckova L, Paulenda T, Kerndl M, Mogilenko DA, Lizotte K, Swain A, Hayes S, Sheldon RD, Kim H, Kapadnis U, Ellis AE, Isaguirre C, Burdess S, Laha A, Amarasinghe GK, Chubukov V, Roddy TP, Diamond MS, Jones RG, Simons DM, Artyomov MN (2021 Mar 9). Itaconate confers tolerance to late NLRP3 inflammasome activation. Cell reports, 34(10), 108756. . ID: 33691097.

24.) Kilgour MK, MacPherson S, Zacharias LG, Ellis AE, Sheldon RD, Liu EY, Keyes S, Pauly B, Carleton G, Allard B, Smazynski J, Williams KS, Watson PH, Stagg J, Nelson BH, DeBerardinis RJ, Jones RG, Hamilton PT, Lum JJ (2021 Jan). 1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer. Science advances, 7(4), . . ID: 33523930.

Description:

The VAI Mass Spectrometry Core (MSC) is committed to developing scientific partnerships with research labs to develop and deploy LC/MS and GC/MS methods specifically tailored to meet the needs of every project. The MSC houses a comprehensive suite of technologies and staff expertise to deliver high quality metabolomics, lipidomics, and proteomics capabilities to VARI scientists and collaborators. The process begins with experimental design support to ensure samples are handled properly, necessary controls are included, and the study is sufficiently powered. Analytical capabilities are combined with custom informatics and statistics solutions to enable faster analysis and more approachable data interpretation. Specific capabilities in the MSC include: Metabolomics and Lipidomics – Three liquid chromatography-mass spectrometry (LC/MS) systems (Thermo Orbitrap ID-X, Thermo Orbitrap Exploris 240, and Agilent 6470 QQQ) and three gas chromatography (GC)/MS systems (Agilent 5977b (2), Thermo 7610 ISQ) are dedicated to small molecule analysis. These instruments deploy an array of standard methods, annotated with a chemical library of over 1000 compounds, to maximize compound coverage in every sample. For metabolomics these methods routinely detect 200+ compounds including TCA cycle intermediates, glycolysis, nucleotides, amino acids, urea cycle, vitamins, cofactors tryptophan/kynurenine metabolism, acyl-CoA’s, acyl-carnitines, polyamines, and others. For lipidomics, 500+ lipid species are routinely annotated including phospholipids, ceramides, triacylglycerides, cardiolipins, cholesterol esters, and more. These methods can be operated in an untargeted manner, allowing for screening for biomarkers and novel metabolites/lipids, and in the context of stable isotope tracing, which allows for assessment of metabolic movement. Further, in line with the scientific partnership mission of the MSC, custom methods are routinely developed to quantitate project-specific compounds of interest. Proteomics – Two nano LC/MS systems (Orbitrap Eclipse and Orbitrap Exploris 480) are dedicated to protein analysis. The expertise and instrumentation will readily make available many proteomics applications including bottom-up quantitative proteomics, tandem mass-tag proteomics, post-translational modification analysis (including phosphoproteomics and histone PTM characterization), protein-protein interactions, intact protein structural elucidation, and more.. Bioinformatics – The MSC has a staff bioinformatician who is dedicated to developing and maintaining informatics pipelines for mass spectrometry data analysis and visualization. This custom data visualization platform transforms daunting excel documents into communicative and interactive figures. Additional layers of data and analysis available through an intuitive user interface, researchers can dive as deep into metabolic pathways and quantitative analyses as demanded by their research questions. Flexible and comprehensive data reporting allows clients to download processed data in excel as well as figures for publication and presentation. The bioinformatician further enables project specific informatics and statistics solutions to ensure robust and informative results for every research question. Major equipment in the facility includes: • Thermo Scientific Orbitrap ID-X LC/MS • Thermo Scientific Orbitrap Exploris 240 LC/MS • Thermo Scientific Orbitrap Eclipse nanoLC/MS • Thermo Scientific Orbitrap Exploris 480 nanoLC/MS • Agilent 6470 Triple Quadrupole LC/MS • Agilent Infinity 1290II UPLC • Agilent 5977B GC/MS (2) • Thermo Scientific ISQ7610 EI/CI enabled GC/MS