Elena Sánchez‐López

Leiden University Medical Center

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Marı́a Luisa Marina

Universidad de Alcalá

María Castro‐Puyana

Universidad de Alcalá

Martin Giera

Netherlands Metabolomics Centre

Antonio L. Crego

Universidad de Alcalá

Samuel Bernardo‐Bermejo

Universidad de Alcalá

Zhengjin Jiang

Jinan University

Francisco Javier Lucio-Cazaña

Universidad de Alcalá

Marieke Griffioen

Leiden University Medical Center

Erik B. van den Akker

Leiden University Medical Center

Hendrik Veelken

Leiden University Medical Center

Cooperative Institutions

Leiden University Medical Center

Leiden University

The Netherlands Cancer Institute

Oncode Institute

University of Liège

Universidad de Alcalá

University of Amsterdam

Netherlands Metabolomics Centre

Amsterdam University Medical Centers

The Wistar Institute

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UHPLC-MS-based untargeted metabolomic strategy to reveal the metabolic differences between cisplatin first- and second-generation apoptotic bodies from HK-2 cells

Microchemical Journal (2024)

Samuel Bernardo‐Bermejo María Castro‐Puyana Elena Sánchez‐López Ana B. Fernández‐Martínez Francisco Javier Lucio-Cazaña

During the process of programmed cell death (apoptosis), the disassembly of apoptotic cells gives rise to apoptotic bodies (ABs) which play an important role in the pathogenesis of different diseases. ABs from renal human proximal tubular cells HK-2 on naïve cells was not always the same: ABs directly generated after exposure of human proximal tubular epithelial HK-2 cells to chemotherapeutic agent cisplatin (1st generation ABs) triggered apoptosis and inhibited cell proliferation, whereas ABs induced by 1st generation ABs (2nd generation ABs) enhanced HK-2 cell proliferation. To shed light on the mechanisms involved in these disparate ABs' effects, a study of the changes in the metabolome of 1st and 2nd generation ABs produced by HK-2 cells in the cisplatin setting was performed by a reversed-phase ultra-high-performance liquid chromatography-mass spectrometry (RP-UHPLC-MS) untargeted metabolomic approach. Thus, ABs fluid and extracellular fluid from 1st and 2nd generation ABs were analyzed to obtain as much information as possible of the metabolites of these extracellular vesicles. Principal components analysis and partial least square discriminant analysis were conducted to find the statistically significant differences between both groups. A good clustering of each group was observed and variable importance in the projection values were selected to choose the molecular features which were identified according to the Metabolomics Standard Initiative (MSI) guidelines. Finally, the biological relevance of the achieved results was discussed.

Metabolome

Extracellular Vesicles

10.1016/j.microc.2024.110406

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Citations (3)

Untargeted HILIC-MS-Based Metabolomics Approach to Evaluate Coffee Roasting Process: Contributing to an Integrated Metabolomics Multiplatform

Molecules (2020)

Raquel Pérez‐Míguez María Castro‐Puyana Elena Sánchez‐López Merichel Plaza Marı́a Luisa Marina

An untargeted metabolomics strategy using hydrophilic interaction chromatography-mass spectrometry (HILIC-MS) was developed in this work enabling the study of the coffee roasting process. Green coffee beans and coffee beans submitted to three different roasting degrees (light, medium, and strong) were analyzed. Chromatographic separation was carried out using water containing 10 mM ammonium formate with 0.2 % formic acid (mobile phase A) and acetonitrile containing 10 mM ammonium formate with 0.2 % formic acid (mobile phase B). A total of 93 molecular features were considered from which 31 were chosen as the most statistically significant using variable in the projection values. 13 metabolites were tentatively identified as potential biomarkers of the coffee roasting process using this metabolomic platform. Results obtained in this work were complementary to those achieved using orthogonal techniques such as reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) and capillary electrophoresis-mass spectrometry (CE-MS) since only one metabolite was found to be common between HILIC-MS and RPLC-MS platforms (caffeoylshikimic acid isomer) and other between HILIC-MS and CE-MS platforms (choline). On the basis of these results, an untargeted metabolomics multiplatform is proposed in this work based on the integration of the three orthogonal techniques as a powerful tool to expand the coverage of the roasted coffee metabolome.

Roasting

Metabolome

10.3390/molecules25040887

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Citations (20)

Chiral Separations by Capillary Electrophoresis

Elena Sánchez‐López María Castro‐Puyana Marı́a Luisa Marina Antonio L. Crego

Abstract The enantiomeric separation of chiral compounds is nowadays a promising topic in analytical sciences. CE is considered as a well‐established tool to perform chiral separations of a wide range of analytes in different research fields such as pharmaceutical, food and chemical industries, and clinical and environmental laboratories. Due to its numerous advantages such as high efficiency, simplicity, and low consumption of reagents, chiral selectors, and samples, CE plays an important role in the separation of enantiomers. Advantages and limitations of the different CE modes are displayed in the present chapter, discussing their possibilities and the actual trends. Hyphenation with MS detection is also discussed, highlighting the potential of this coupling as well as its weaknesses and, the most commonly used strategies to minimize its drawbacks. Most recent and relevant applications of chiral CE are summarized and illustrated with tables including the analysis of pharmaceutical, biological, and environmental samples, food and beverages, and agrochemicals. Finally, concluding remarks and future trends are also included describing the actual state of the art and challenges of chiral CE techniques.

Simplicity

10.1002/9783527678129.assep043

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Citations (23)

Recent contributions of capillary electrophoresis to neuroscience

TrAC Trends in Analytical Chemistry (2015)

Elena Sánchez‐López Cristina Montealegre Antonio L. Crego Marı́a Luisa Marina

10.1016/j.trac.2014.12.008

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Citations (21)

Lipidomics analysis in drug discovery and development

Current Opinion in Chemical Biology (2022)

Sarantos Kostidis Elena Sánchez‐López Martin Giera

Despite being a relatively new addition to the Omics' landscape, lipidomics is increasingly being recognized as an important tool for the identification of druggable targets and biochemical markers. In this review we present recent advances of lipid analysis in drug discovery and development. We cover current state of the art technologies which are constantly evolving to meet demands in terms of sensitivity and selectivity. A careful selection of important examples is then provided, illustrating the versatility of lipidomics analysis in the drug discovery and development process. Integration of lipidomics with other omics', stem-cell technologies, and metabolic flux analysis will open new avenues for deciphering pathophysiological mechanisms and the discovery of novel targets and biomarkers.

Druggability

Drug Development

Identification

10.1016/j.cbpa.2022.102256

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Citations (21)

Separation of N-derivatized di- and tri-peptide stereoisomers by micro-liquid chromatography using a quinidine-based monolithic column – Analysis of l-carnosine in dietary supplements

Journal of Chromatography A (2015)

Qiqin Wang Elena Sánchez‐López Hai Han Huihui Wu Peijie Zhu

Carnosine

10.1016/j.chroma.2015.09.016

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Citations (20)

Mapping AML heterogeneity – multi-cohort transcriptomic analysis identifies novel clusters and divergent ex-vivo drug responses

medRxiv (Cold Spring Harbor Laboratory) (2023)

Jeppe Severens Emin Onur Karakaslar Bert A. van der Reijden Elena Sánchez‐López Redmar R. van den Berg

Abstract Subtyping of acute myeloid leukaemia (AML) is predominantly based on recurrent genetic abnormalities, but recent literature indicates that transcriptomic phenotyping holds immense potential to further refine AML classification. Here we integrated five AML transcriptomic datasets with corresponding genetic information to provide an overview (n=1224) of the transcriptomic AML landscape. Consensus clustering identified 17 robust patient clusters which improved identification of CEBPA -mutated patients with favourable outcomes, and uncovered transcriptomic subtypes for KMT2A rearrangements (2), NPM1 mutations (5), and AML with myelodysplasia-related changes (AML-MRC) (5). Transcriptomic subtypes of KMT2A , NPM1 and AML-MRC showed distinct mutational profiles, cell type differentiation arrests and immune properties, suggesting differences in underlying disease biology. Moreover, our transcriptomic clusters show differences in ex-vivo drug responses, even when corrected for differentiation arrest and superiorly capture differences in drug response compared to genetic classification. In conclusion, our findings underscore the importance of transcriptomics in AML subtyping and offer a basis for future research and personalised treatment strategies. Our transcriptomic compendium is publicly available and we supply an R package to project clusters to new transcriptomic studies.

NPM1

CEBPA

Subtyping

10.1101/2023.03.29.23287896

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Citations (0)

Evaluation of the potential of a quinidine-based monolithic column on the enantiomeric separation of herbicides by nano-liquid chromatography

Microchemical Journal (2015)

Qiaoxuan Zhang V. S. Çavuscedilla ̃gil Elena Sánchez‐López María Ángeles García Zhengjin Jiang

Mecoprop

Dicamba

10.1016/j.microc.2015.05.011

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Citations (18)

Exploratory Metabolomic Analysis Based on Reversed-Phase Liquid Chromatography–Mass Spectrometry to Study an In Vitro Model of Hypoxia-Induced Metabolic Alterations in HK-2 Cells

International Journal of Molecular Sciences (2021)

Samuel Bernardo‐Bermejo Elena Sánchez‐López Lei Tan Selma Benito-Martínez Zhengjin Jiang

Oxygen deficiency in cells, tissues, and organs can not only prevent the proper development of biological functions but it can also lead to several diseases and disorders. In this sense, the kidney deserves special attention since hypoxia can be considered an important factor in the pathophysiology of both acute kidney injury and chronic kidney disease. To provide better knowledge to unveil the molecular mechanisms involved, new studies are necessary. In this sense, this work aims to study, for the first time, an in vitro model of hypoxia-induced metabolic alterations in human proximal tubular HK-2 cells because renal proximal tubules are particularly susceptible to hypoxia. Different groups of cells, cultivated under control and hypoxia conditions at 0.5, 5, 24, and 48 h, were investigated using untargeted metabolomic approaches based on reversed-phase liquid chromatography–mass spectrometry. Both intracellular and extracellular fluids were studied to obtain a large metabolite coverage. On the other hand, multivariate and univariate analyses were carried out to find the differences among the cell groups and to select the most relevant variables. The molecular features identified as affected metabolites were mainly amino acids and Amadori compounds. Insights about their biological relevance are also provided.

Hypoxia

Hypoxia-Inducible Factors

Metabolic pathway

10.3390/ijms22147399

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Citations (4)

Mapping AML heterogeneity - multi-cohort transcriptomic analysis identifies novel clusters and divergent ex-vivo drug responses

Leukemia (2024)

Jeppe Severens Emin Onur Karakaslar Bert A. van der Reijden Elena Sánchez‐López Redmar R. van den Berg

Subtyping of acute myeloid leukaemia (AML) is predominantly based on recurrent genetic abnormalities, but recent literature indicates that transcriptomic phenotyping holds immense potential to further refine AML classification. Here we integrated five AML transcriptomic datasets with corresponding genetic information to provide an overview (n = 1224) of the transcriptomic AML landscape. Consensus clustering identified 17 robust patient clusters which improved identification of CEBPA-mutated patients with favourable outcomes, and uncovered transcriptomic subtypes for KMT2A rearrangements (2), NPM1 mutations (5), and AML with myelodysplasia-related changes (AML-MRC) (5). Transcriptomic subtypes of KMT2A, NPM1 and AML-MRC showed distinct mutational profiles, cell type differentiation arrests and immune properties, suggesting differences in underlying disease biology. Moreover, our transcriptomic clusters show differences in ex-vivo drug responses, even when corrected for differentiation arrest and superiorly capture differences in drug response compared to genetic classification. In conclusion, our findings underscore the importance of transcriptomics in AML subtyping and offer a basis for future research and personalised treatment strategies. Our transcriptomic compendium is publicly available and we supply an R package to project clusters to new transcriptomic studies.

NPM1

CEBPA

Subtyping

10.1038/s41375-024-02137-6

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Citations (8)