Research

01 Population-scale Health Studies

Molecular assays with quantitative reliability, deep coverage and throughput are essential for patient cohort or population-scale studies. SysMeC develops robotics-based automation workflows, fast LC-MS methods and automated data processing solutions to offer several metabolomic and lipidomic panels of high complexity with short turnaround time.

02 Disease mechanisms

The research themes of our centre focus on elucidating the molecular mechanisms by which organisms regulate metabolism, a topic highly relevant to many diseases. We study lipid transporters and enzymes, organelle physiology, metabolic fluxes and inter-organ communication.

Our centre is founded on mass spectrometry-based analytical biochemistry and bioinformatics, through which we analyse in vitro systems, animal models and human cohorts. Metabolic profiling provides a quantifiable readout of healthy and pathological states.

In the future, the limited chemical analyses used in medicine today will eventually be replaced by more comprehensive metabolic profiling that will better describe metabolic changes, distinguish disease stages and improve diagnosis and treatment.

03 Mass spectrometry technology

Mass spectrometry (MS) is a powerful analytical technique that plays a central role in lipidomics and metabolomics. MS enables sensitive detection, identification and quantitation of a wide range of small molecules in complex biological samples. By coupling with separation techniques, such as liquid chromatography (LC), supercritical fluid chromatography (SFC) or gas chromatography (GC), MS provides detailed insights into the molecular composition and structure of lipids and metabolites. This information is essential for understanding cellular processes, biological mechanisms and diseases.

The SysMeC team has extensive expertise in both low- and high-resolution MS, applying these platforms to analyze a broad spectrum of lipids and metabolites across diverse biological samples. Our laboratories are equipped with state-of-the-art mass spectrometers, including Triple quadrupoles, Q-ToFs, Ion Mobility, and Orbitrap from different vendors (Agilent Technologies, Sciex, Thermo Scientific, Shimadzu, Waters).

Chocholoušková M, Torta F. Fast and comprehensive lipidomic analysis using supercritical fluid chromatography coupled with low and high resolution mass spectrometry. J Chromatogr A. 2025 Mar 29;1745:465742. doi: 10.1016/j.chroma.2025.465742.
Chang, J.K., Teo, G., Pewzner-Jung, Y. et al. Q-RAI data-independent acquisition for lipidomic quantitative profiling. Sci Rep 13, 19281 (2023). https://doi.org/10.1038/s41598-023-46312-8
Gao L, Cazenave-Gassiot A, Burla B, Wenk MR, Torta F. Dual mass spectrometry as a tool to improve annotation and quantification in targeted plasma lipidomics. Metabolomics. 2020 Apr 17;16(5):53. doi: 10.1007/s11306-020-01677-z.

04 Harmonization

Harmonization of lipidomic and metabolomic assays aims to ensure comparability of analysis results, obtained within and across different laboratories. This is crucial to improve the reproducibility of measurements and for clinical translation of developed assays.

At SysMeC, we implement experimental and data analysis workflows to ensure the standardization of our assays. Instead of prescribing fixed protocols, we believe that developing a set of best practices, including rigorous QA/QC, can achieve harmonization at various sites and, importantly, across different instrument platforms.

SysMeC has coordinated an international ring trial that resulted in an excellent agreement in the analysis of plasma ceramides using commutable standards and reference materials. SysMeC also develops software tools to support the harmonization efforts within the lab and in the community

05 Metabolic Tissue Atlas

SysMeC is also dedicated to generating comprehensive molecular atlases of human and animal cells and tissues, especially the metabolomic and lipidomic data in combination with other genomic, transcriptomic and proteomic data. In combination with other bioinformatic approaches developed in house, our global profiling strategy aims to describe tissue-specific metabolic rewiring and track systemic shifts in interorgan metabolic communication under varying physiological and pathological conditions. To date, we have successfully built multi-tissue metabolome atlases for mouse models in cardiometabolic diseases and profiled tissue-plasma metabolome landscape in human cohorts. These efforts provide valuable data resources that empower translational discovery.

Muralidharan S, Shimobayashi M, Ji S, Burla B, Hall MN, Wenk MR, Torta F. A reference map of sphingolipids in murine tissues. Cell Rep. 2021 Jun 15;35(11):109250. doi: 10.1016/j.celrep.2021.109250.
Ren H, Triebl A, Muralidharan S, Wenk MR, Xia Y, Torta F. Mapping the distribution of double bond location isomers in lipids across mouse tissues. Analyst. 2021 Jun 14;146(12):3899-3907. doi: 10.1039/d1an00449b.

06 Multi-omic integration through network biology

The utility of metabolome and lipidome-wide profiling data can be elevated via integration with complementary modalities such as quantitative genomic, epigenomic, transcriptomic and proteomic profiles of metabolic enzymes, transporters and other signaling molecules modulating the metabolic activity. We develop elegant statistical computing strategies to identify biochemical pathways and novel relationships between small molecules and gene products from multi-omic data. This work is enabled through innovative algorithm for graph inference of ultrahigh-dimensional multi-omic data and reconciliation with experimentally validated biochemical pathways.

07 Quantitative Assays for Small Molecules

Quantitation of small molecules is essential for elucidating their roles in health and disease. Our research group specializes in analytical approaches for lipid and polar metabolite quantitation, utilizing advanced chromatographic techniques coupled with either low- or high-resolution mass spectrometry. In lipidomics, we focus on both lipid species separation and lipid class separation, where coelution of internal standards and endogenous lipids leads to more accurate quantitation.

Our methodologies are aligned with the guidelines and best practices set within our research community, including rigorous quality control measures, to ensure the highest levels of precision and data reliability. We have extensive experience in quantifying a wide range of molecules across various biological matrices, such as body fluids, cells, tissues and cellular organelles.

Chocholoušková M, Torta F. Fast and comprehensive lipidomic analysis using supercritical fluid chromatography coupled with low and high resolution mass spectrometry. J Chromatogr A. 2025 Mar 29;1745:465742. doi: 10.1016/j.chroma.2025.465742.

08 Metabolite panels

Our targeted metabolomics panel revolves around metabolites from the central carbon metabolism pathways. These pathways are known to be perturbed in various metabolic diseases, including diabetes, cardiovascular diseases, kidney diseases, and even cancer. Being quantitative assays, they are suitable for use in basic research discovery and in clinical screenings requiring absolute quantitation.

Amino acid
Amino acids and other nitrogen-containing compounds
Acylcarnitine (Fatty oxidation pathway)
Kynurenine pathway
Organic acid (TCA cycle)
Glycolysis and pentose phosphate pathway
Short to long chain fatty acids

Targeted metabolomics analysis approach to unravel the biofilm formation pathways of Enterococcus faecalis clinical isolates. Suriyanarayanan T, Lee LS, Han SHY, Ching J, Seneviratne CJ. Int Endod J. 2024 Oct;57(10):1505-1520. doi: 10.1111/iej.14110. Epub 2024 Jun 18.
Urine Tricarboxylic Acid Cycle Metabolites and Risk of End-stage Kidney Disease in Patients With Type 2 Diabetes. Liu JJ, Liu S, Zheng H, Lee J, Gurung RL, Chan C, Lee LS, Ang K, Ching J, Kovalik JP, Tavintharan S, Sum CF, Sharma K, Coffman TM, Lim SC. J Clin Endocrinol Metab. 2025 Jan 21;110(2):e321-e329. doi: 10.1210/clinem/dgae199.

09 Lipidomics

Over many years, we have developed and accumulated a unique set of experiences that apply state-of-the-art mass spectrometry for lipidomic analysis in various applications, documented in multiple peer reviewed journals. Our laboratory hosts a combination of mass spectrometers (low and high resolution), methods (shotgun- and chromatography-based) and data analysis capabilities. This is supported by our knowledge of lipid pathway regulation in health and disease and in different organisms. Several lipid panels are used for robust, sensitive, quantitative and large-scale lipidomics. These panels cover a wide range of lipid classes, such as cholesteryl esters, triacylglycerols, diacylglycerols, deoxyceramides, ceramides, monohexosylceramides, dihexosylceramides, trihexosylceramides, gangliosides, phosphatidylglycerols, phosphatidylethanolamines, phosphatidylinositols, phosphatidylserines, phosphatidylcholines and their lyso- forms, acylcarnitines and sphingomyelins.

Recommendations for good practice in MS-based lipidomics. Köfeler HC, Ahrends R, Baker ES, Ekroos K, Han X, Hoffmann N, Holčapek M, Wenk MR, Liebisch G. J Lipid Res. 2021;62:100138. doi: 10.1016/j.jlr.2021.100138. Epub 2021 Oct 16. PMID: 34662536
Introduction of a Lipidomics Scoring System for data quality assessment. Hoffmann N, Ahrends R, Baker ES, Ekroos K, Han X, Holčapek M, Liebisch G, Wenk MR, Xia Y, Köfeler HC. J Lipid Res. 2025 Apr 30:100817. doi: 10.1016/j.jlr.2025.100817. Online ahead of print. PMID: 40316026

Other more specialized assays are used to measure:

Bile Acids, including primary and secondary species, as well as their conjugated and sulfated forms.
Oxylipins: with more than 100 various oxylipins belonging to eicosanoids and docosanoids, derived from the oxidation of polyunsaturated fatty acids.
Total Fatty Acids: using GC/MS following lipid hydrolysis and derivatization, enabling the separation and quantification of omega-3 and omega-6 fatty acids.

10 Exposomics

Exposure assessment is an essential component in food safety risk analysis that estimates the level of intake of hazards. When combined with hazard assessment, populations with excess exposures that would lead to adverse health outcomes could be identified and managed. We aim to an evidence-based approach to understand the dietary exposure contribution to biomarker levels. We put emphasis on the screening and surveillance of food-hazard combinations having greater influence on the overall exposure to the hazards. To achieve this, we collaborate with academic, public and commercial partners to achieve the following goals:

Evaluate the occurrence of biomarkers of exposure to chemical hazards of interest in the general population in Singapore and establish the baseline level of exposure.
Estimate the individual food consumption and correlate with the exposure biomarkers level.
Examine the distribution of chemical hazards exposure in different population groups.

To this end, we develop more than several mass spectrometry-based quantitative panels for exposure biomarkers and aim to offer comprehensive report on exposure potential in the context of precision assessment.

Integrated analysis of per- and polyfluoroalkyl substances and plasma lipidomics profiles in multi-ethnic Asian subjects for exposome research. Narasimhan K, Vaitheeswari, Choi E, Chandran NS, Eriksson JG, Bendt AK, Torta F, Mir SA. Environ Health. 2024 Nov 28;23(1):105. doi: 10.1186/s12940-024-01145-4

11 Metabolic Flux

Our centre provides experimental support for metabolic flux analysis by

advising on experimental design based on aims
selection of suitable stable isotopes for tracing
biological interpretation of data

This work supports research in cellular metabolism, metabolic engineering, and systems biology.

Triebl A, Wenk MR. Analytical Considerations of Stable Isotope Labelling in Lipidomics. Biomolecules. 2018 Nov 16;8(4):151. doi: 10.3390/biom8040151.

12 Publications

Find here the updated publications list contributed by our lab.