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Metabolomics Studies Benefit Biomedical Research

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Professor Dr. Thomas Hankemeier, Head of the Division of Systems Biomedicine and Pharmacology, LACDR

LACDR is a center of excellence for multidisciplinary research into drug discovery and development, with a strong focus on metabolomics. As part of its research activities, the center uses SCIEX instruments to develop metabolomics platforms offering high throughput analysis and broad coverage of various metabolites.

The Division of Analytical Biosciences is part of the Leiden Academic Centre for Drug Research (LACDR) in the Netherlands, an institute at the forefront of research and education in drug discovery and development.

The Analytical Biosciences group, led by Professor Dr. Thomas Hankemeier, head of the Division of Systems Biomedicine and Pharmacology at LACDR and co-founder of the world’s first organ-on-a-chip company, MIMETAS, has extensive experience in metabolomics for biomarker discovery and frequently participates in large-scale cohort studies.

Thomas explained, “Our group is focused on the development of new technologies and analytical methods for large-scale studies involving the measurement of metabolites, as well as miniaturization to allow metabolomics to be performed on a smaller scale. We apply these methods to the analysis of clinical samples, and also have our own special interest biochemical research projects.”

Thomas continued, “I originally wanted to study medicine, but finally chose chemistry because I realized that this would give me the opportunity to investigate the mechanisms behind diseases, allowing the development of more effective drugs. Understanding the metabolic drivers for vascular problems is a particular interest of mine, and we are currently looking into the science behind vascular destabilization, or loss of the integrity of the microvasculature, together with the Leiden University Medical Center. We believe studying vascular destabilization will allow us to find biomarkers for early dementia. This metabolomics work contributes to the Rotterdam Study, a large-scale population study at the Erasmus Medical Centre, where I work closely with Professor Cornelia van Duijn in my position as a Medical Delta Professor of Translational Epidemiology. The Rotterdam Study is following the health of thousands of individuals over a period of more than 20 years to investigate the onset and progression of dementia and other diseases. Another neurodegenerative disease we are investigating is Parkinson’s, where around 10 to 15 percent of cases are caused by mitochondrial dysfunction. Our aim is to identify this subpopulation, and then to identify and explore potential therapies to treat the cause of the disease.”

“At the moment, sample numbers for any given project range from tens or hundreds up to a few thousand, depending on the study design. The more diverse the study cohort, the more samples must be analyzed to obtain meaningful results. Ultimately, we have a vision of offering high throughput clinical metabolomics and lipidomics, and mass spectrometry has an important role to play. It is our primary detection technology, coupled to LC, GC, or even CE systems.”

“I had previously used SCIEX mass spectrometers and, although it was more than 10 years ago, this meant that I was already familiar with the company and its instruments. Around three or four years ago, we became interested in the SCIEX TripleTOF® and QTRAP systems, which perfectly complement our existing mass spectrometers. We invested in two TripleTOF instruments and two QTRAP instruments, and SCIEX collaborated with us to help develop methods on these systems. We also have CE-MS capabilities, again using SCIEX instruments, and are developing some novel introduction systems for this technique.”

“Cell metabolism is different in 2D cultures compared to 3D, and this has generated an interest in the development of organ-on-a-chip devices, offering more relevant, metabolically-sound in vitro models. We are engaged in translational research in this area, and this has become a driver for miniaturization of some of our assays. The QTRAP Systems offer excellent sensitivity for this, making them ideal for targeted methods to determine low levels of metabolites produced using organ-on-a-chip models.”

“THE QTRAPS OFFER EXCELLENT SENSITIVITY FOR THIS, MAKING THEM IDEAL FOR TARGETED METHODS TO DETERMINE LOW LEVELS OF METABOLITES PRODUCED USING ORGAN-ON-A-CHIP MODELS.”

“The TripleTOF Systems are used in many of our projects and perform very well. They have a wide dynamic range and are very stable, enabling excellent, large-scale quantification of metabolites, which is important for our research. We have also developed an untargeted metabolomics workflow, analyzing diverse sample matrices that vary considerably in their complexity, and plan to explore the potential of SWATH Data Acquisition. In addition, we are currently evaluating the SCIEX Lipidyzer Platform, and are interested in collaborating with the company to develop these applications further.”

“After sales service and support is as important as the instruments’ performance, stability, and reliability. SCIEX has given us all the technical support we have needed so far, helping us to quickly establish new protocols for our different projects. I am very happy to work with them,” Thomas concluded.

Find out more about LACDR >Find out more about SCIEX TripleTOF systems >

This article is from the 2018 edition of the SCIEX VISION journal. You can download the full version of the journal which includes over 10 customer research stories.

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