1. Multiplex quantitation strategy for lipid mediators using liquid chromatography-tandem mass spectrometry

Lipid mediators including prostaglandins, leukotrienes, platelet-activating factor and many other bioactive lipid metabolites are attracting great attention as disease-related or physiologically important molecules. Comprehensive analysis of known lipid mediators is a useful unbiased method in disease mechanism studies, and the lipid mediator profile is a useful parameter that characterizes disease status as well. We have developed an original multiplex quantification method for trace amounts of lipid mediators using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We are developing more sensitive and rapid methods that cover more lipid mediators, which meet the demands on various large-scale studies and high-throughput screening approaches.

2. Lipid biomarker discovery

Lipid biomarker discovery by liquid chromatography-mass spectrometry-based method requires high-level integration of chromatography and mass spectrometry, which ensures lipid separation, semi-quantitative detection, and identification. We are collaborating with industries to solve known difficulties in lipid chromatography, develop differential analysis and feature-extraction methods, and establish an intelligent analytical system linked with lipid database.

3. Methods for clinical samples

Human clinical samples such as blood, urine, feces, and tissue biopsies vary much as compared with controlled animal studies. Furthermore, sampling and storage conditions are not always optimized for lipid analysis. We are developing techniques for handling clinical samples for a practical lipidomics analysis.

4. Lipidomics strategy for lipid metabolism

A simple lipidomics analysis provides large datasets that describe the amount-based profile of lipidome. However, it is not sufficient to investigate the status of lipid metabolic pathway, because changes in metabolic flux do not always reflect to static amount of metabolites. To overcome this, we develop a flux-oriented lipidomics analysis using stable-isotope tracers.

5. Lipid biomarker/lipid mediator discovery using animal models

Appling the latest lipidomics technologies to the analysis of the animal models of various diseases including metabolic disease, we are trying to discover novel lipid biomarkers. We also analyze various gene-deficient mice and transgenic mice to seek important lipid markers, lipid mediators, and lipid profiles.

6. Discovery of novel lipid mediator metabolizing pathways

Although major biosynthetic and catabolic pathways for classical lipid mediators have been well documented so far, there are still possibilities for yet unidentified lipid mediator metabolizing pathways in vivo. We have obtained a preliminary data for novel lipid mediator producing pathway using gene-deficient mice. Using the latest lipidomics techniques to the cell cultures and animal models, we will elucidate a novel lipid mediator related pathway and its biological significance.

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