Bioanalysis Zone

An author’s perspective: Yie Hou Lee on Retention time bracketing for targeted sphingolipidomics by LC–MS/MS

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To help provide insight into the recent article published in Bioanalysis: Retention time bracketing for targeted sphingolipidomics by liquid chromatography–tandem mass spectrometry, we spoke to author Yie Hou Lee, Assistant Professor and Principal Scientist KK Women’s and Children’s Hospital (Singapore). Yie Hou explains why this is an important area for bioanalysis and worthy of publication.

YHLDr Yie Hou Lee is an Assistant Professor at Duke-NUS Medical School (Singapore), Principal Scientist at KK Hospital (Singapore) and Principal Investigator at MIT’s Research Enterprise in Singapore, CAMP (Critical Analytics for Manufacturing Personalized Medicine). He is leading the basic and translational research of endometriosis using an integrated systems biology and cellular approach to deeply characterize the disease, discover biomarkers and identify ‘druggable’ molecular and cellular targets. His curiosity reaches out to other disease domains where cross-disciplinary concepts can be interfaced to advance our understanding of endometriosis.

1. What inspired you to work in this field of bioanalysis?
Biology has traditionally lagged behind physical sciences in terms of understanding the essential characteristics of systems, their interactions and changes under normal and perturbed conditions. One of the main reasons is the lack of robust quantification that allows the systematic description of organisms and the biological processes. This discrepancy has an immense impact on the applied/translational branches of biology including life sciences and biomedicine. In modern biology, the advent of bioanalytical tools such as chromatography and mass spectrometry has transformed this, facilitating the accurate characterization of the ‘nuts and bolts’ of biological systems and very often the large-scale quantification of hundreds to thousands of biological compounds. In turn, this has changed the way we view biology and medicine, enabling the construction of digital maps of biological systems and having detailed views of them. Through these bioanalytical tools, we could then begin to characterize how physiological systems are perturbed in cells, tissues and organisms, for biomarker discovery and understanding the mechanisms underlying diseases such as endometriosis and dengue and in characterization of cellular secreted compounds for optimized cell-release therapeutic products.

2. What impact would you like to see/expect to see as a result of your publication?
Structurally diverse sphingolipids might confer different biological activities and potencies. Our publication demonstrates how one could reliably probe sphingolipidomes, even for sphingolipids that do not comply to chemical synthesis standards, for their confident identification and quantification. Thus, the ability to identify which peaks conform to the structurally unique sphingolipid species helps  to evaluate the changes in sphingolipidome profiles across different experimental conditions and diseases.

Our publication also highlights the particular need for more careful evaluation of endogenous sphingolipids as standards for quantification. Thoughtful selection of appropriate sphingolipid standards has tremendous effects on accuracy of readouts and will vary according to the biological matrix used. The complexity of biofluids and tissues warrants an even heightened need for thorough evaluation. The same can be said of the use of other lipids and biological compounds for quantification.

3. What are the next steps for your research and this field of bioanalysis?
Understanding the functional impact of these sphingolipids on cellular functions such as proliferation, apoptosis, migration and angiogenesis. Translation of these results along with the bioanalytical methods for medicine are some long-term goals that I hope to accomplish.

4. Are there any researchers/projects/technologies that you are watching at the moment, and any you think we should be keeping an eye on?
Cell-based therapies or advanced cell therapeutics. During the past 15 years, cell-based therapies have dramatically changed the field of regenerative medicine and treatment of cancers. Innovations in cell-based therapies have accelerated in recent years due to re-programming of differentiated cells into induced pluripotent stem cells, gene editing (CRISPR-Cas9), chimeric antigen receptor T-cell therapies, personalized vaccinations and understanding of individualized metabolic profiles. For all of these innovative developments, growing evidence has revealed that secreted soluble and/or paracrine factors are responsible for mediating many of the immunomodulatory and regenerative cellular functions. As such, the reliable characterization of cellular secreted products is paramount to fundamentally understanding cellular function and optimizing secreted factors and cellular processes for efficacious and safe medical treatments. Thus, bioanalytics continue to play a critical role and the evolution of bioanalytical technologies that revolve around accuracy, sensitivity, reproducibility, rapidness and pluggability are anticipated for scaled-up production.

5. Do you have any advice for anyone who may be interested in working in this field?
Keep up-to-date on fields that demand innovation that improves the techniques and also allows them to be adapted within the specific needs of the field(s).

Author affiliations: KK Women’s & Children’s Hospital, Singapore; Singapore-MIT Alliance for Research and Technology-Critical Analytics for Manufacturing Personalized Medicine (SMART-CAMP).

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Reference: Zhu L, Zhou J, Liang C et al. Retention time bracketing for targeted sphingolipodomics by liquid chromatography–tandem mass spectrometry. Bioanalysis. 11(3): 185–201 (2019).

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