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2. NMNAT2 is a druggable target to drive neuronal NAD production

Author

Tribble, James R., Jöe, Melissa, Varricchio, Carmine, Otmani, Amin, Canovai, Alessio, Habchi, Baninia, Daskalakis, Evangelia, Chaleckis, Romanas, Loreto, Andrea, Gilley, Jonathan, Wheelock, Craig E., Jóhannesson, Gauti, Wong, Raymond C. B., Coleman, Michael P., Brancale, Andrea, and Williams, Pete A.

Published
2024
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6. Glutarate regulates T cell metabolism and anti-tumour immunity

Author

Minogue, Eleanor, Cunha, Pedro P., Wadsworth, Brennan J., Grice, Guinevere L., Sah-Teli, Shiv K., Hughes, Rob, Bargiela, David, Quaranta, Alessandro, Zurita, Javier, Antrobus, Robin, Velica, Pedro, Barbieri, Laura, Wheelock, Craig E., Koivunen, Peppi, Nathan, James A., Foskolou, Iosifina P., and Johnson, Randall S.

Published
2023
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7. Urinary eicosanoid levels in early life and risk of atopic disease in childhood

Author

Chen, Liang, Brustad, Nicklas, Kim, Min, Luo, Yang, Wang, Tingting, Ali, Mina, Prince, Nicole, Chen, Yulu, Chu, Su, Begum, Sofina, Mendez, Kevin, Kelly, Rachel S., Schoos, Ann-Marie, Rasmussen, Morten A., Zurita, Javier, Kolmert, Johan, Stokholm, Jakob, Litonjua, Augusto, Weiss, Scott T., Bønnelykke, Klaus, Wheelock, Craig E., Lasky-Su, Jessica, and Chawes, Bo

Published
2024
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10. Metabolite signatures associated with microRNA miR-143-3p serve as drivers of poor lung function trajectories in childhood asthma

Author

Mendez, Kevin M., Begum, Sofina, Tiwari, Anshul, Sharma, Rinku, Chen, Qingwen, Kelly, Rachel S., Prince, Nicole, Huang, Mengna, Kachroo, Priyadarshini, Chu, Su H., Chen, Yulu, Lee-Sarwar, Kathleen, Broadhurst, David I., Reinke, Stacey N., Gerszten, Robert, Clish, Clary, Avila, Lydiana, Celedón, Juan C., Wheelock, Craig E., Weiss, Scott T., McGeachie, Michael, and Lasky-Su, Jessica A.

Published
2024
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15. Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective

Author

Zhang, Pei, Carlsten, Christopher, Chaleckis, Romanas, Hanhineva, Kati, Huang, Mengna, Isobe, Tomohiko, Koistinen, Ville M, Meister, Isabel, Papazian, Stefano, Sdougkou, Kalliroi, Xie, Hongyu, Martin, Jonathan W, Rappaport, Stephen M, Tsugawa, Hiroshi, Walker, Douglas I, Woodruff, Tracey J, Wright, Robert O, and Wheelock, Craig E

Subjects
Chemical Engineering, Engineering, Environmental Sciences, Pollution and Contamination, Generic health relevance, Good Health and Well Being, Environmental Science and Management, Environmental Engineering, Environmental Biotechnology, Chemical engineering, Pollution and contamination
Abstract

The concept of the exposome was introduced over 15 years ago to reflect the important role that the environment exerts on health and disease. While originally viewed as a call-to-arms to develop more comprehensive exposure assessment methods applicable at the individual level and throughout the life course, the scope of the exposome has now expanded to include the associated biological response. In order to explore these concepts, a workshop was hosted by the Gunma University Initiative for Advanced Research (GIAR, Japan) to discuss the scope of exposomics from an international and multidisciplinary perspective. This Global Perspective is a summary of the discussions with emphasis on (1) top-down, bottom-up, and functional approaches to exposomics, (2) the need for integration and standardization of LC- and GC-based high-resolution mass spectrometry methods for untargeted exposome analyses, (3) the design of an exposomics study, (4) the requirement for open science workflows including mass spectral libraries and public databases, (5) the necessity for large investments in mass spectrometry infrastructure in order to sequence the exposome, and (6) the role of the exposome in precision medicine and nutrition to create personalized environmental exposure profiles. Recommendations are made on key issues to encourage continued advancement and cooperation in exposomics.

Published
2021

19. Implementing precision medicine in a regionally organized healthcare system in Sweden

Author

Fioretos, Thoas, Wirta, Valtteri, Cavelier, Lucia, Berglund, Eva, Friedman, Mikaela, Akhras, Michael, Botling, Johan, Ehrencrona, Hans, Engstrand, Lars, Helenius, Gisela, Fagerqvist, Therese, Gisselsson, David, Gruvberger-Saal, Sofia, Gyllensten, Ulf, Heidenblad, Markus, Höglund, Kina, Jacobsson, Bo, Johansson, Maria, Johansson, Åsa, Soller, Maria Johansson, Landström, Maréne, Larsson, Pär, Levin, Lars-Åke, Lindstrand, Anna, Lovmar, Lovisa, Lyander, Anna, Melin, Malin, Nordgren, Ann, Nordmark, Gunnel, Mölling, Paula, Palmqvist, Lars, Palmqvist, Richard, Repsilber, Dirk, Sikora, Per, Stenmark, Bianca, Söderkvist, Peter, Stranneheim, Henrik, Strid, Tobias, Wheelock, Craig E., Wadelius, Mia, Wedell, Anna, Edsjö, Anders, and Rosenquist, Richard

Published
2022
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21. Mild COVID-19 imprints a long-term inflammatory eicosanoid- and chemokine memory in monocyte-derived macrophages

Author

Bohnacker, Sina, Hartung, Franziska, Henkel, Fiona, Quaranta, Alessandro, Kolmert, Johan, Priller, Alina, Ud-Dean, Minhaz, Giglberger, Johanna, Kugler, Luisa M., Pechtold, Lisa, Yazici, Sarah, Lechner, Antonie, Erber, Johanna, Protzer, Ulrike, Lingor, Paul, Knolle, Percy, Chaker, Adam M., Schmidt-Weber, Carsten B., Wheelock, Craig E., and Esser-von Bieren, Julia

Published
2022
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22. Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma

Author

Kachroo, Priyadarshini, Stewart, Isobel D., Kelly, Rachel S., Stav, Meryl, Mendez, Kevin, Dahlin, Amber, Soeteman, Djøra I., Chu, Su H., Huang, Mengna, Cote, Margaret, Knihtilä, Hanna M., Lee-Sarwar, Kathleen, McGeachie, Michael, Wang, Alberta, Wu, Ann Chen, Virkud, Yamini, Zhang, Pei, Wareham, Nicholas J., Karlson, Elizabeth W., Wheelock, Craig E., Clish, Clary, Weiss, Scott T., Langenberg, Claudia, and Lasky-Su, Jessica A.

Published
2022
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24. Tackling the Complexity of the Exposome: Considerations from the Gunma University Initiative for Advanced Research (GIAR) Exposome Symposium.

Author

Zhang, Pei, Arora, Manish, Chaleckis, Romanas, Isobe, Tomohiko, Jain, Mohit, Meister, Isabel, Melén, Erik, Perzanowski, Matthew, Torta, Federico, Wenk, Markus R, and Wheelock, Craig E

Subjects
environment, epigenetics, exposome, exposure, metabolomics, Analytical Chemistry, Biochemistry and Cell Biology, Clinical Sciences
Abstract

The attempt to describe complex diseases by solely genetic determination has not been successful. There is increasing recognition that the development of disease is often a consequence of interactions between multiple genetic and environmental factors. To date, much of the research on environmental determinants of disease has focused on single exposures generally measured at a single time point. In order to address this limitation, the concept of the exposome has been introduced as a comprehensive approach, studying the full complement of environmental exposures from conception onwards. However, exposures are vast, dynamic, and diverse, and only a small proportion can be reasonably measured due to limitations in technology and feasibility. In addition, the interplay between genes and exposure as well as between different exposures is complicated and multifaceted, which leads to difficulties in linking disease or health outcomes with exposures. The large numbers of collected samples require well-designed logistics. Furthermore, the immense data sets generated from exposome studies require a significant computational investment for both data analysis and data storage. This report summarizes discussions during an international exposome symposium held at Gunma University in Japan regarding the concept of the exposome, challenges in exposome research, and future perspectives in the field.

Published
2019

25. Metabolomics of neonatal blood spots reveal distinct phenotypes of pediatric acute lymphoblastic leukemia and potential effects of early-life nutrition

Author

Petrick, Lauren M, Schiffman, Courtney, Edmands, William MB, Yano, Yukiko, Perttula, Kelsi, Whitehead, Todd, Metayer, Catherine, Wheelock, Craig E, Arora, Manish, Grigoryan, Hasmik, Carlsson, Henrik, Dudoit, Sandrine, and Rappaport, Stephen M

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Pediatric Cancer, Pediatric, Hematology, Clinical Research, Perinatal Period - Conditions Originating in Perinatal Period, Nutrition, Rare Diseases, Prevention, Childhood Leukemia, Cancer, 4.1 Discovery and preclinical testing of markers and technologies, Reproductive health and childbirth, Adolescent, Age Factors, Biomarkers, Bottle Feeding, Breast Feeding, California, Child, Child, Preschool, Dried Blood Spot Testing, Energy Metabolism, Female, Humans, Incidence, Infant, Infant Formula, Infant Nutritional Physiological Phenomena, Infant, Newborn, Lipids, Male, Metabolomics, Neonatal Screening, Nutritional Status, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Protective Factors, Risk Assessment, Risk Factors, Breastfeeding, Maternal BMI, Pre-B ALL, t(12, 21) translocation, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Early-life exposures are believed to influence the incidence of pediatric acute lymphoblastic leukemia (ALL). Archived neonatal blood spots (NBS), collected within the first days of life, offer a means to investigate small molecules that reflect early-life exposures. Using untargeted metabolomics, we compared abundances of small-molecule features in extracts of NBS punches from 332 children that later developed ALL and 324 healthy controls. Subjects were stratified by early (1-5 y) and late (6-14 y) diagnosis. Mutually-exclusive sets of metabolic features - representing putative lipids and fatty acids - were associated with ALL, including 9 and 19 metabolites in the early- and late-diagnosis groups, respectively. In the late-diagnosis group, a prominent cluster of features with apparent 18:2 fatty-acid chains suggested that newborn exposure to the essential nutrient, linoleic acid, increased ALL risk. Interestingly, abundances of these putative 18:2 lipids were greater in infants who were fed formula rather than breast milk (colostrum) and increased with the mother's pre-pregnancy body mass index. These results suggest possible etiologic roles of newborn nutrition in late-diagnosis ALL.

Published
2019

26. MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines 1

Author

Burla, Bo, Arita, Makoto, Arita, Masanori, Bendt, Anne K, Cazenave-Gassiot, Amaury, Dennis, Edward A, Ekroos, Kim, Han, Xianlin, Ikeda, Kazutaka, Liebisch, Gerhard, Lin, Michelle K, Loh, Tze Ping, Meikle, Peter J, Orešič, Matej, Quehenberger, Oswald, Shevchenko, Andrej, Torta, Federico, Wakelam, Michael JO, Wheelock, Craig E, and Wenk, Markus R

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Clinical Research, Good Health and Well Being, Blood Chemical Analysis, Blood Specimen Collection, Demography, Female, Guidelines as Topic, Humans, Lipids, Male, Mass Spectrometry, Reference Standards, clinical trials, diagnostic tools, lipids, mass spectrometry, absolute concentrations, clinical research, data sharing, National Institute of Standards and Technology Standard Reference Material 1950, quality control, Biochemistry and Cell Biology, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medical biochemistry and metabolomics
Abstract

Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.

Published
2018

27. Effect of perfluoroalkyl exposure in pregnancy and infancy on intrauterine and childhood growth and anthropometry. Sub study from COPSAC2010 birth cohort

Author

Sevelsted, Astrid, Gürdeniz, Gözde, Rago, Daniela, Pedersen, Casper-Emil Tingskov, Lasky-Su, Jessica A., Checa, Antonio, Zhang, Pei, Wheelock, Craig E., Normann, Stine S., Kristensen, David M., Rasmussen, Morten Arendt, Schullehner, Jörg, Sdougkou, Kalliroi, Martin, Jonathan W., Stokholm, Jakob, Bønnelykke, Klaus, Bisgaard, Hans, and Chawes, Bo

Published
2022
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30. Targeting a scavenger receptor on tumor-associated macrophages activates tumor cell killing by natural killer cells

Author

Eisinger, Silke, Sarhan, Dhifaf, Boura, Vanessa F., Ibarlucea-Benitez, Itziar, Tyystjärvi, Sofia, Oliynyk, Ganna, Arsenian-Henriksson, Marie, Lane, David, Wikström, Stina L., Kiessling, Rolf, Virgilio, Tommaso, Gonzalez, Santiago F., Kaczynska, Dagmara, Kanatani, Shigeaki, Daskalaki, Evangelia, Wheelock, Craig E., Sedimbi, Saikiran, Chambers, Benedict J., Ravetch, Jeffrey V., and Karlsson, Mikael C. I.

Published
2020

31. Deciphering lipid structures based on platform-independent decision rules

Author

Hartler, Jürgen, Triebl, Alexander, Ziegl, Andreas, Trötzmüller, Martin, Rechberger, Gerald N, Zeleznik, Oana A, Zierler, Kathrin A, Torta, Federico, Cazenave-Gassiot, Amaury, Wenk, Markus R, Fauland, Alexander, Wheelock, Craig E, Armando, Aaron M, Quehenberger, Oswald, Zhang, Qifeng, Wakelam, Michael JO, Haemmerle, Guenter, Spener, Friedrich, Köfeler, Harald C, and Thallinger, Gerhard G

Subjects
Biological Sciences, Algorithms, Animals, Chromatography, Liquid, Lipids, Liver, Mice, Molecular Structure, Reproducibility of Results, Sensitivity and Specificity, Tandem Mass Spectrometry, Technology, Medical and Health Sciences, Developmental Biology, Biological sciences
Abstract

We achieve automated and reliable annotation of lipid species and their molecular structures in high-throughput data from chromatography-coupled tandem mass spectrometry using decision rule sets embedded in Lipid Data Analyzer (LDA; http://genome.tugraz.at/lda2). Using various low- and high-resolution mass spectrometry instruments with several collision energies, we proved the method's platform independence. We propose that the software's reliability, flexibility, and ability to identify novel lipid molecular species may now render current state-of-the-art lipid libraries obsolete.

Published
2017

32. Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma.

Author

Bowden, John A, Heckert, Alan, Ulmer, Candice Z, Jones, Christina M, Koelmel, Jeremy P, Abdullah, Laila, Ahonen, Linda, Alnouti, Yazen, Armando, Aaron M, Asara, John M, Bamba, Takeshi, Barr, John R, Bergquist, Jonas, Borchers, Christoph H, Brandsma, Joost, Breitkopf, Susanne B, Cajka, Tomas, Cazenave-Gassiot, Amaury, Checa, Antonio, Cinel, Michelle A, Colas, Romain A, Cremers, Serge, Dennis, Edward A, Evans, James E, Fauland, Alexander, Fiehn, Oliver, Gardner, Michael S, Garrett, Timothy J, Gotlinger, Katherine H, Han, Jun, Huang, Yingying, Neo, Aveline Huipeng, Hyötyläinen, Tuulia, Izumi, Yoshihiro, Jiang, Hongfeng, Jiang, Houli, Jiang, Jiang, Kachman, Maureen, Kiyonami, Reiko, Klavins, Kristaps, Klose, Christian, Köfeler, Harald C, Kolmert, Johan, Koal, Therese, Koster, Grielof, Kuklenyik, Zsuzsanna, Kurland, Irwin J, Leadley, Michael, Lin, Karen, Maddipati, Krishna Rao, McDougall, Danielle, Meikle, Peter J, Mellett, Natalie A, Monnin, Cian, Moseley, M Arthur, Nandakumar, Renu, Oresic, Matej, Patterson, Rainey, Peake, David, Pierce, Jason S, Post, Martin, Postle, Anthony D, Pugh, Rebecca, Qiu, Yunping, Quehenberger, Oswald, Ramrup, Parsram, Rees, Jon, Rembiesa, Barbara, Reynaud, Denis, Roth, Mary R, Sales, Susanne, Schuhmann, Kai, Schwartzman, Michal Laniado, Serhan, Charles N, Shevchenko, Andrej, Somerville, Stephen E, St John-Williams, Lisa, Surma, Michal A, Takeda, Hiroaki, Thakare, Rhishikesh, Thompson, J Will, Torta, Federico, Triebl, Alexander, Trötzmüller, Martin, Ubhayasekera, SJ Kumari, Vuckovic, Dajana, Weir, Jacquelyn M, Welti, Ruth, Wenk, Markus R, Wheelock, Craig E, Yao, Libin, Yuan, Min, Zhao, Xueqing Heather, and Zhou, Senlin

Subjects
Humans, Lipids, Observer Variation, Reproducibility of Results, Reference Standards, International Cooperation, Benchmarking, Lipid Metabolism, Laboratory Proficiency Testing, National Institute of Standards and Technology, Standard Reference Material 1950, fatty acyls, glycerolipids, lipids, phospholipids, quality control, quantitation, sphingolipids, sterols, Clinical Research, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology
Abstract

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

Published
2017

34. Mirnaome-Metabolome Wide Association Study Reveals Effects of Mirna Regulation in Eosinophilia and Airflow Obstruction in Childhood Asthma

Author

Sharma, Rinku, primary, Mendez, Kevin, additional, Begum, Sofina, additional, Chu, Su H., additional, Prince, Nicole, additional, Hecker, Julian, additional, Kelly, Rachel S., additional, Chen, Qingwen, additional, Wheelock, Craig E., additional, Celedón, Juan, additional, Clish, Clary, additional, Gertszen, Robert, additional, Tantisira, Kelan G., additional, Weiss, Scott T., additional, Lasky-Su, Jessica A., additional, and McGeachie, Michael, additional

Published
2024
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36. Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease

Author

Akawi, Nadia, Checa, Antonio, Antonopoulos, Alexios S., Akoumianakis, Ioannis, Daskalaki, Evangelia, Kotanidis, Christos P., Kondo, Hidekazu, Lee, Kirsten, Yesilyurt, Dilan, Badi, Ileana, Polkinghorne, Murray, Akbar, Naveed, Lundgren, Julie, Chuaiphichai, Surawee, Choudhury, Robin, Neubauer, Stefan, Channon, Keith M., Torekov, Signe S., Wheelock, Craig E., and Antoniades, Charalambos

Published
2021
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37. Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD.

Author

Naz, Shama, Kolmert, Johan, Yang, Mingxing, Reinke, Stacey N, Kamleh, Muhammad Anas, Snowden, Stuart, Heyder, Tina, Levänen, Bettina, Erle, David J, Sköld, C Magnus, Wheelock, Åsa M, and Wheelock, Craig E

Subjects
Humans, Pulmonary Disease, Chronic Obstructive, Phosphoric Diester Hydrolases, MicroRNAs, Respiratory Function Tests, Chromatography, Liquid, Cross-Sectional Studies, Smoking, Sex Factors, Oxidative Stress, Middle Aged, Sweden, Female, Male, Statistics as Topic, Metabolomics, Pulmonary Disease, Chronic Obstructive, Chromatography, Liquid, Respiratory System, Medical and Health Sciences
Abstract

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I-II/A-B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography-high resolution mass spectrometry metabolomics platform.Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10-7). Sex stratification indicated that the separation was driven by females (p=2.4×10-7) relative to males (p=4.0×10-4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10-3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p

Published
2017

38. A Method for Measuring Metabolism in Sorted Subpopulations of Complex Cell Communities Using Stable Isotope Tracing.

Author

Roci, Irena, Gallart-Ayala, Hector, Watrous, Jeramie, Jain, Mohit, Wheelock, Craig E, and Nilsson, Roland

Subjects
Biochemistry and Cell Biology, Biological Sciences, Cell Cycle, Cells, Cultured, Chromatography, Liquid, Flow Cytometry, Humans, Isotope Labeling, Isotopes, Mass Spectrometry, Metabolomics, Biochemistry, Issue 120, sorted cells, cell sorter, flow cytometry, metabolite extraction, mass spectrometry, metabolomics, cell cycle, Psychology, Cognitive Sciences, Biochemistry and cell biology
Abstract

Mammalian cell types exhibit specialized metabolism, and there is ample evidence that various co-existing cell types engage in metabolic cooperation. Moreover, even cultures of a single cell type may contain cells in distinct metabolic states, such as resting or cycling cells. Methods for measuring metabolic activities of such subpopulations are valuable tools for understanding cellular metabolism. Complex cell populations are most commonly separated using a cell sorter, and subpopulations isolated by this method can be analyzed by metabolomics methods. However, a problem with this approach is that the cell sorting procedure subjects cells to stresses that may distort their metabolism. To overcome these issues, we reasoned that the mass isotopomer distributions (MIDs) of metabolites from cells cultured with stable isotope-labeled nutrients are likely to be more stable than absolute metabolite concentrations, because MIDs are formed over longer time scales and should be less affected by short-term exposure to cell sorting conditions. Here, we describe a method based on this principle, combining cell sorting with liquid chromatography-high resolution mass spectrometry (LC-HRMS). The procedure involves analyzing three types of samples: (1) metabolite extracts obtained directly from the complex population; (2) extracts of "mock sorted" cells passed through the cell sorter instrument without gating any specific population; and (3) extracts of the actual sorted populations. The mock sorted cells are compared against direct extraction to verify that MIDs are indeed not altered by the cell sorting procedure itself, prior to analyzing the actual sorted populations. We show example results from HeLa cells sorted according to cell cycle phase, revealing changes in nucleotide metabolism.

Published
2017

39. Glutamine Links Obesity to Inflammation in Human White Adipose Tissue

Author

Petrus, Paul, Lecoutre, Simon, Dollet, Lucile, Wiel, Clotilde, Sulen, André, Gao, Hui, Tavira, Beatriz, Laurencikiene, Jurga, Rooyackers, Olav, Checa, Antonio, Douagi, Iyadh, Wheelock, Craig E., Arner, Peter, McCarthy, Mark, Bergo, Martin O., Edgar, Laurienne, Choudhury, Robin P., Aouadi, Myriam, Krook, Anna, and Rydén, Mikael

Published
2020
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40. Metabolite Profiling and Stable Isotope Tracing in Sorted Subpopulations of Mammalian Cells

Author

Roci, Irena, Gallart-Ayala, Hector, Schmidt, Angelika, Watrous, Jeramie, Jain, Mohit, Wheelock, Craig E, and Nilsson, Roland

Subjects
Medical Biochemistry and Metabolomics, Analytical Chemistry, Biomedical and Clinical Sciences, Chemical Sciences, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Carbon Isotopes, Cell Cycle, Chromatography, Liquid, Flow Cytometry, HeLa Cells, Humans, Mass Spectrometry, Metabolomics, Nitrogen Isotopes, Hela Cells, Other Chemical Sciences, Medical biochemistry and metabolomics, Analytical chemistry, Chemical engineering
Abstract

Biological samples such as tissues, blood, or tumors are often complex and harbor heterogeneous populations of cells. Separating out specific cell types or subpopulations from such complex mixtures to study their metabolic phenotypes is challenging because experimental procedures for separation may disturb the metabolic state of cells. To address this issue, we developed a method for analysis of cell subpopulations using stable isotope tracing and fluorescence-activated cell sorting followed by liquid chromatography-high-resolution mass spectrometry. To ensure a faithful representation of cellular metabolism after cell sorting, we benchmarked sorted extraction against direct extraction. While peak areas differed markedly with lower signal for amino acids but higher signal for nucleotides, mass isotopomer distributions from sorted cells were generally in good agreement with those obtained from direct extractions, indicating that they reflect the true metabolic state of cells prior to sorting. In proof-of-principle studies, our method revealed metabolic phenotypes specific to T cell subtypes, and also metabolic features of cells in the committed phase of the cell division cycle. Our approach enables studies of a wide range of adherent and suspension cell subpopulations, which we anticipate will be of broad importance in cell biology and biomedicine.

Published
2016

41. A walnut-enriched diet for 2 years changes the serum oxylipin profile in healthy older persons

Author

Cofán, Montserrat, primary, Checa, Antonio, additional, Serra-Mir, M., additional, Roth, I., additional, Valls-Pedret, C., additional, Lopez-Illamola, A., additional, Doménech, M., additional, Rajaram, Sujatha, additional, Lázaro, Iolanda, additional, Sabaté, Joan, additional, Ros, Emilio, additional, Wheelock, Craig E., additional, and Sala-Vila, Aleix, additional

Published
2023
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42. Sphingolipid classes and the interrelationship with pediatric asthma and asthma risk factors

Author

Chen, Yulu, primary, Checa, Antonio, additional, Zhang, Pei, additional, Huang, Mengna, additional, Kelly, Rachel S., additional, Kim, Min, additional, Chen, Yih‐Chieh S., additional, Lee‐Sarwar, Kathleen A., additional, Prince, Nicole, additional, Mendez, Kevin M., additional, Begum, Sofina, additional, Kachroo, Priyadarshini, additional, Chu, Su H., additional, Stokholm, Jakob, additional, Bønnelykke, Klaus, additional, Litonjua, Augusto A., additional, Bisgaard, Hans, additional, Weiss, Scott T., additional, Chawes, Bo L., additional, Wheelock, Craig E., additional, and Lasky‐Su, Jessica A., additional

Published
2023
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43. The re-emerging role of linoleic acid in paediatric asthma

Author

Naughten, Sarah, primary, Ecklu-Mensah, Gertrude, additional, Constantino, Gailan, additional, Quaranta, Alessandro, additional, Schulkers Escalante, Keriann, additional, Bai-Tong, Shiyu, additional, Gilbert, Jack, additional, Leibel, Sandra, additional, Wheelock, Craig E., additional, and Leibel, Sydney, additional

Published
2023
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44. ELIXIR and Toxicology: a community in development

Author

Martens, Marvin, primary, Stierum, Rob, additional, Schymanski, Emma L., additional, Evelo, Chris T., additional, Aalizadeh, Reza, additional, Aladjov, Hristo, additional, Arturi, Kasia, additional, Audouze, Karine, additional, Babica, Pavel, additional, Berka, Karel, additional, Bessems, Jos, additional, Blaha, Ludek, additional, Bolton, Evan E., additional, Cases, Montserrat, additional, Damalas, Dimitrios Ε., additional, Dave, Kirtan, additional, Dilger, Marco, additional, Exner, Thomas, additional, Geerke, Daan P., additional, Grafström, Roland, additional, Gray, Alasdair, additional, Hancock, John M., additional, Hollert, Henner, additional, Jeliazkova, Nina, additional, Jennen, Danyel, additional, Jourdan, Fabien, additional, Kahlem, Pascal, additional, Klanova, Jana, additional, Kleinjans, Jos, additional, Kondic, Todor, additional, Kone, Boï, additional, Lynch, Iseult, additional, Maran, Uko, additional, Martinez Cuesta, Sergio, additional, Ménager, Hervé, additional, Neumann, Steffen, additional, Nymark, Penny, additional, Oberacher, Herbert, additional, Ramirez, Noelia, additional, Remy, Sylvie, additional, Rocca-Serra, Philippe, additional, Salek, Reza M., additional, Sallach, Brett, additional, Sansone, Susanna-Assunta, additional, Sanz, Ferran, additional, Sarimveis, Haralambos, additional, Sarntivijai, Sirarat, additional, Schulze, Tobias, additional, Slobodnik, Jaroslav, additional, Spjuth, Ola, additional, Tedds, Jonathan, additional, Thomaidis, Nikolaos, additional, Weber, Ralf J.M., additional, van Westen, Gerard J.P., additional, Wheelock, Craig E., additional, Williams, Antony J., additional, Witters, Hilda, additional, Zdrazil, Barbara, additional, Županič, Anže, additional, and Willighagen, Egon L., additional

Published
2023
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46. Author Correction: Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma

Author

Kachroo, Priyadarshini, Stewart, Isobel D., Kelly, Rachel S., Stav, Meryl, Mendez, Kevin, Dahlin, Amber, Soeteman, Djøra I., Chu, Su H., Huang, Mengna, Cote, Margaret, Knihtilä, Hanna M., Lee-Sarwar, Kathleen, McGeachie, Michael, Wang, Alberta, Wu, Ann Chen, Virkud, Yamini, Zhang, Pei, Wareham, Nicholas J., Karlson, Elizabeth W., Wheelock, Craig E., Clish, Clary, Weiss, Scott T., Langenberg, Claudia, and Lasky-Su, Jessica A.

Published
2022
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47. High-Dose Simvastatin Exhibits Enhanced Lipid-Lowering Effects Relative to Simvastatin/Ezetimibe Combination Therapy

Author

Snowden, Stuart G, Grapov, Dmitry, Settergren, Magnus, D'Alexandri, Fabio Luiz, Haeggström, Jesper Z, Fiehn, Oliver, Hyötyläinen, Tuulia, Pedersen, Theresa L, Newman, John W, Orešič, Matej, Pernow, John, and Wheelock, Craig E

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Cardiovascular, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Aged, Analysis of Variance, Anticholesteremic Agents, Azetidines, Ceramides, Cholesterol, Cholesterol, LDL, Discriminant Analysis, Double-Blind Method, Drug Administration Schedule, Drug Combinations, Ezetimibe, Simvastatin Drug Combination, Female, Humans, Hypercholesterolemia, Male, Middle Aged, Phosphatidylcholines, Simvastatin, Sphingomyelins, Treatment Outcome, Triglycerides, eicosanoids, ezetimibe, hydroxymethylglutaryl-CoA reductase inhibitors, lipids, mass spectrometry, simvastatin, Genetics, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

Statins are the frontline in cholesterol reduction therapies; however, their use in combination with agents that possess complimentary mechanisms of action may achieve further reductions in low-density lipoprotein cholesterol. Thirty-nine patients were treated with either 80 mg simvastatin (n=20) or 10 mg simvastatin plus 10 mg ezetimibe (n=19) for 6 weeks. Dosing was designed to produce comparable low-density lipoprotein cholesterol reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects. Baseline and post-treatment plasma were analyzed for lipid mediators (eg, eicosanoids and endocannabinoids) and structural lipids by liquid chromatography tandem mass spectrometry. After statistical analysis and orthogonal projections to latent structures multivariate modeling, no changes were observed in lipid mediator levels, whereas global structural lipids were reduced in response to both monotherapy (R(2)Y=0.74; Q(2)=0.66; cross-validated ANOVA P=7.0×10(-8)) and combination therapy (R(2)Y=0.67; Q(2)=0.54; cross-validated ANOVA P=2.6×10(-5)). Orthogonal projections to latent structures modeling identified a subset of 12 lipids that classified the 2 treatment groups after 6 weeks (R(2)Y=0.65; Q(2)=0.61; cross-validated ANOVA P=5.4×10(-8)). Decreases in the lipid species phosphatidylcholine (15:0/18:2) and hexosyl-ceramide (d18:1/24:0) were the strongest discriminators of low-density lipoprotein cholesterol reductions for both treatment groups (q

Published
2014

50. Correction to: Mild COVID-19 imprints a long-term inflammatory eicosanoid- and chemokine memory in monocyte-derived macrophages

Author

Bohnacker, Sina, Hartung, Franziska, Henkel, Fiona, Quaranta, Alessandro, Kolmert, Johan, Priller, Alina, Ud-Dean, Minhaz, Giglberger, Johanna, Kugler, Luisa M., Pechtold, Lisa, Yazici, Sarah, Lechner, Antonie, Erber, Johanna, Protzer, Ulrike, Lingor, Paul, Knolle, Percy, Chaker, Adam M., Schmidt-Weber, Carsten B., Wheelock, Craig E., and Esser-von Bieren, Julia

Published
2022
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