Metabolomics & Bioenergetics Core

Overview

Metabolomics and Bioenergetics Core

Van Andel Institute’s Metabolomics and Bioenergetics Core enables scientists to investigate the metabolic mechanisms of disease through state-of-the-art respirometry, metabolite profiling, stable isotope tracing and untargeted analysis.

Contact

For questions, please contact Core Director Dr. Ryan Sheldon.

Contact Dr. Ryan Sheldon

Our Impact

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  • 171 studies published from Nov. 1, 2020 to Oct. 1, 2021
  • 68 studies in high-impact journals from Nov. 1, 2020-Oct. 1, 2021
  • 41 clinical trials launched

VAI’s Metabolomics and Bioenergentics Core offers a range of comprehensive metabolism and mass spectrometry services along with consulting and training for VAI investigators.

SERVICES

  • Targeted metabolite profiling
  • Stable isotope tracing
  • Quantitative metabolomics for select metabolites
  • Targeted method development
  • Untargeted metabolomics
  • In-depth data analysis, visualization, and biological interpretation

CONTACT
For questions, please contact Research Scientist and Core Manager Dr. Ryan Sheldon at Ryan.Sheldon@vai.org.

Primary use: Untargeted and semi-untargeted metabolite profiling and stable isotope labeling

Capabilities

  • High-resolution/accurate mass data acquisition
  • Up to four chromatographic separations per sample to maximize metabolite coverage
  • MS2 fragmentation for compound identification and library matching
  • MSn fragmentation for structural elucidation

Specifications

  • Up to 500k resolution (FWHM)
  • < 2ppm mass accuracy
  • Electrospray ionization
  • Dual Vanquish UHPLC
  • Data dependent acquisition
  • CID and HCD fragmentation

Primary use: Targeted polar metabolite profiling and custom targeted method development

Capabilities

  • Ion-paired negative mode profiling of ~250 polar metabolites, including amino acids, nucleotides, carboxylates and sugar phosphates
  • dMRM mode limits transition monitoring only to retention windows of interest to maximize compounds detected per run
  • Highly reproducible ion-paired chromatography
  • High sensitivity and specificity of targeted compounds
  • Second UHPLC system for targeted method development of compounds not amenable to ion-pairing.

Specifications

  • Sub-femtogram detection limits (compound dependent)
  • Electrospray ionization

Primary use: Targeted metabolite profiling of central carbon metabolism and custom targeted method development

Capabilities

  • Profiling, quantitation, and stable isotope labeling of most amino acids and TCA cycle intermediates
  • In-source compound fragmentation for positive ID

Specifications

  • Sub-femtogram detection limits (compound dependent)
  • Electron-impact ionization

Primary use: Measure OCR and ECAR of live cells in a 96-well plate format. OCR and ECAR rates are key indicators of mitochondrial respiration and glycolysis and these measurements provide a systems-level view of cellular metabolic function in cultured cells and ex vivo samples

Capabilities

  • Four-port injection system and automated mixing allows real-time detection of responses to substrates, inhibitors and other compounds. Temperature is maintained at 37oC
  • A 96-well plate allows multiple conditions to be run at once. The system is optimized for compound screening and dose-response studies.
  • As few as 5,000 cells per well may be analyzed at high sensitivity (depending on cell type)
  • System is compatible with many different sample types

Specifications

  • 96 assay wells
  • 2µL microchamber volume

Below are compounds that the Core routinely measures on its platforms. The Core is continuously expanding this list, so please contact Core Manager Dr. Ryan Sheldon if your compounds of interest are not listed. Please note that not all compounds will be detected in every sample type.

Compounds

  • 2-Aminobutyrate+B2:B46
  • 4-Guanidinobutyrate
  • 4-Hydroxyglutamate
  • 4-Hydroxyproline
  • 5-Methoxytryptamine
  • Alanine
  • Aminoadipate
  • Arginine
  • Argininosuccinate
  • Asparagine
  • Aspartate
  • Beta-Alanine
  • Carnitine
  • Citrulline
  • Creatine phosphate
  • Creatine
  • Creatinine
  • Cystathionine
  • Cystine
  • Folinic acid
  • gamma-Aminobutyrate
  • gamma-Glu-Cys
  • Glutamate
  • Glutamine
  • Glycine
  • Histidine
  • Homocitrate
  • Homocysteine
  • Homocystine
  • Homoserine
  • Isoleucine
  • Leucine
  • Lysine
  • Methionine
  • N-Acetylarginine
  • N-Acetylasparagine
  • N-Acetylaspartate
  • N-Acetylglutamic acid
  • N-Acetylglutamine
  • N-Acetylglycine
  • N-Acetylisoleucine
  • N-Acetyllysine
  • N-Acetylvaline
  • N-Carbamoyl-aspartate
  • N-Carbamyl-glutamate
  • N-Methylgluamate
  • O-Phosphoserine
  • Ornithine
  • O-Succinylhomoserine
  • Phenylalanine
  • Proline
  • Pyroglutamate
  • S-(2′-Aminoethyl)-cysteine
  • Sarcosine
  • Serine
  • Threonine
  • Tryptophan
  • Tyrosine
  • Valine
  • Pyruvate
  • Acetyl-CoA
  • CoA
  • Citrate
  • Isocitrate
  • Aconitate
  • α-ketoglutarate
  • 2-hydrxyglutarate
  • Succinate
  • Fumarate
  • Malate
  • Aspartate
  • 2-hydroxybutyrate
  • 3-hydroxybutyrate
  • Adipate
  • Itaconate
  • Citramalate
  • Glutarate
  • GSH
  • GSSG
  • NAD+
  • NADH
  • NADP+
  • NADPH
  • FAD+
  • FADH2
  • Formate
  • Acetate
  • Propanoate
  • Butyrate
  • Isobutyrate
  • Valerate
  • Isovalerate
  • 2-Methylbutyrate
  • Hexanoate
  • 2-Methylvalerate
  • 3-Methylvalerate
  • 4-Methylvalerate
  • Acetoacetate
  • Heptanoate
  • 2-Methylhexanoate
  • Octanoate
  • 2-Ketobutyrate
  • 2-Ketoisocaproate
  • 3-methyl-2-oxobutyrate
  • 3-Methyl-2-Oxovalerate
  • Nonanoic Acid
  • Decanoic Acid
  • Tetradecanoic Acid (Myristic Acid)
  • Pentadecanoic Acid
  • Hexadecanoic Acid (Palmitic Acid)
  • Heptadecanoic Acid
  • Octadecanoic Acid (Stearic Acid)
  • Eicosanoic Acid
  • Docosanoic Acid
  • Tetracosanoic Acid
  • Hexacosanoic Acid
  • Octacosanoic Acid
  • Triacontanoic Acid
  • Adenine
  • Adenosine
  • ADP
  • AMP
  • ATP
  • cAMP
  • CDP
  • cGMP
  • CMP
  • CTP
  • Cytidine
  • Cytosine
  • dADP
  • dAMP
  • dATP
  • dCDP
  • dCMP
  • dCTP
  • Deoxyadenosine
  • Deoxycytidine
  • Deoxyguanosine
  • Deoxyinosine
  • Deoxyuridine
  • Dihydroorotoate
  • dTTP
  • dUTP
  • GDP
  • GTP
  • Guanine
  • Guanosine
  • Hypoxanthine
  • IDP
  • IMP
  • Inosine
  • ITP
  • Orotate
  • S-adenosyl-homocysteine
  • S-adenosyl-methionine
  • TDP
  • Thymidine
  • Thymine
  • UDP
  • UMP
  • Uracil
  • Uridine
  • UTP
  • Xanthine
  • 3-Hydroxyanthranilate
  • 3-Hydroxykynurenine
  • 6-Hydroxynicotinic acid
  • Hydroxyindole-3-acetic acid
  • Indole-3-acetamide
  • Indole-3-acetic acid
  • Indole-3-butyric acid
  • Indole-3-Carboxaldehyde
  • Indole-3-carboxylic acid
  • Indole-3-lactic acid
  • Indole-3-propionic acid
  • Indole-3-pyruvic acidIndoline-2-carboxylate
  • Indoxyl-3-sulfate
  • Kynurenic acid
  • Kynurenine
  • N,N-Dimethylserotonin
  • N,N-Dimethyltryptamine
  • Nicotinamide mononucleotide
  • Nicotinamide N-oxide
  • Nicotinamide
  • Nicotinic acid mononucleotide
  • Nicotinuric acid
  • N-methyl nicotinamide
  • N-methyl Tryptamine
  • N-methylserotonin
  • Picolinic Acid
  • Quinolinic acid
  • Serotonin
  • Tryptamine
  • Tryptophol
  • 3-Phosphoglycerate
  • 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR)
  • Dihydroxyacetone-P
  • Fructose 1,6-biphosphate
  • Fructose-6P
  • Glucose-1P
  • Glucose-6P
  • Glyceraldehyde-3P
  • Phosphoenolpyruvic acid
  • Phosphoribosyl pyrophosphate (PRPP)
  • Pyruvate
  • Ribose (1/5)-P
  • Ribulose-P
  • Sedoheptulose-7P
  • 2-Deoxyglucose-6P
  • 2-Deoxyribose
  • 2-Deoxyribose-5P
  • Arabinose
  • Arabitol (Xylitol)
  • D-Galactosamine
  • D-Gluconic acid
  • D-Maltose
  • D-Mannose
  • D-Xylose
  • Galactonic acid
  • Galactose
  • GDP-Mannose
  • Glucoheptonic acid
  • Gluconic acid delta-lactone
  • Glucosamine-6P
  • Glyceric acid
  • Mannose-1P
  • Melibiose
  • myo-Inositol
  • N-Acetylgalactosamine
  • N-Acetylglucosamine
  • N-Acetylglucosamine-1P
  • N-Acetylglucosamine-6P
  • N-Acetylneuraminic acid
  • Sorbose
  • Trehalose
  • Trehalose-6P
  • UDP-galactose
  • UDP-glucose
  • UDP-Glucuronic acid
  • UDP-N-acetylgalactosamine
  • UDP-N-acetylglucosamine
  • Pyridoxal
  • 4-Pyridoxic acid
  • Pantothenic Acid
  • Pyridoxal-5P
  • Pyridoxamine
  • Pyridoxine
  • Ascorbic acid

Ryan Sheldon, Ph.D.

Core Director and Research Scientist

Carlos Castello, B.A.

Metabolomics Specialist III

Abigail Ellis, B.S.

Metabolomics Specialist II

Christine Isaguirre, B.S.

Metabolomics Specialist II

Hyoungjoo Lee, Ph.D.

MeNu Proteomics Platform Director

Michael Vincent, Ph.D.

Bioinformatics Research Scientist

PUBLICATIONS

Publications containing work performed by VAI’s Metabolomics and Bioenergetics Core are asked to follow these guidelines in their acknowledgements:

  • Acknowledge contributions by Van Andel Institute’s Metabolomics Core by name in the manuscript.
  • Consider authorship for more significant intellectual and planning contributions.
  • Notify Core Services staff of successful publications and awarded grant applications. This assists in tracking and maintaining institutional records, which help inform the Cores’ quality services.

Please note, the Metabolomics Core opened in fall 2019. Papers will be listed here as they are published.

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. Carbon source availability drives nutrient utilization in CD8+ T cells. Cell Metab.

Sheldon RD, Ma EH, DeCamp LM, Williams KS, Jones RG. 2021. Interrogating in vivo T-cell metabolism in mice using stable isotope labeling metabolomic and rapid cell sortingNat Proto.

Izreig S, Gariepy A, Kaymak I, Bridges HR, Donayo AO, Bridon G, DeCamp LM, Kitchen-Goosen SM, Avizonis D, Sheldon RD, Laister R, Minden MD, Johnson NA, Duchaine TF, Rudoltz MS, Yoo S, Pollak MN, Williams KS, Jones RG. 2020. Repression of LKB1 by miR-17~92 sensitizes MYC-dependent lymphoma to biguanide treatmentCell Rep Med.

Roy DG*, Chen J*, Mamane V, Ma EH, Muhire BM, Sheldon RD, Shorstova T, Koning R, Johnson RM, Esaulova E, Williams KS, Hayes S, Steadman M, Samborska B, Swain A, Daigneault A, Chubukov V, Roddy TP, Foulkes W, Pospisilik JA, Dourgeois-Daigneualt, Artyomov MN, Witcher M, Krawczyk CM, Larochelle C, Jones RG. 2020. Methionine metabolism shapes helper T helper cell responses through regulation of epigenetic reprogrammingCell Metab 31(2):250–266.
*Co-first authors
Highlighted in a preview in Cell Metabolism

EH Ma, Verway MJ, Johnson RM, Roy DG, Steadman M, Hayes S, Williams KS, Sheldon RD, Samborska B, Kosinski PA, Kim H, Griss T, Faubert B, Condotta SA, Krawczyk CM, DeBerardinis RJ, Marsh K, Richer MJ, Chubukov V, Roddy T, Jones RG. 2019. Metabolic profiling using stable isotope tracing reveals distinct patterns of glucose utilization by physiologically activated CD8+ T cellsImmunity.