Do Yup Lee

Seoul National University | SNU · Department of Agricultural Biotechnology

Aim Cholesterol homeostasis is associated with Alzheimer's disease (AD). Despite the multitude of cholesterol metabolites, little is known about which metabolites are directly involved in AD pathogenesis and can serve as its potential biomarkers. Methods To identify “hit” metabolites, steroid profiling was conducted in mice with different age, die...

Metformin, a primary anti-diabetic medication, has been anticipated to provide benefits for Alzheimer’s disease (AD), also known as “type 3 diabetes”. Nevertheless, some studies have demonstrated that metformin may trigger AD pathology and even elevate AD risk in humans. Despite this, limited research has elucidated the behavioral outcomes of metfo...

Endocrine-disrupting chemicals (EDCs) are compounds that disturb hormonal homeostasis by binding to receptors. EDCs are metabolized through hepatic enzymes, causing altered transcriptional activities of hormone receptors, and thus necessitating the exploration of the potential endocrinedisrupting activities of EDC-derived metabolites. Accordingly,...

Metformin, a first-line anti-diabetic medication, may provide benefits against the pathogenesis of Alzheimer’s disease (AD) or “type 3 diabetes”. However, studies have demonstrated that metformin treatment may increase the risk of AD and aggravate its pathology. At present, no comprehensive investigation of the cognitive impact of chronic metformin...

A family of signal transduction pathways known as wingless type (Wnt) signaling pathways is essential to developmental processes like cell division and proliferation. Mutation in Wnt signaling results in a variety of diseases, including cancers of the breast, colon, and skin, metabolic disease, and neurodegenerative disease; thus, the Wnt signaling...

Rice (Oryza sativa L.) is a widely consumed food source, and its geographical origin has long been a subject of discussion. In our study, we collected 44 and 20 rice samples from different regions of the Republic of Korea and China, respectively, of which 35 and 29 samples were of white and brown rice, respectively. These samples were analyzed usin...

Fatty acid esters of hydroxyl fatty acids (FAHFAs) are a new family of endogenous lipids that exert anti-inflammatory action. Among the various FAHFA isomers, the dietary source of oleic acid-hydroxy stearic acid (OAHSA) and its anti-inflammatory functions are poorly understood. This study investigated the composition of OAHSA isomers in dietary oi...

The objective of this study was to identify predictable maternal serum signatures of cortisol metabolism during the first trimester of women who are expected to deliver small-for-gestational-age (SGA) neonates. This prospective cohort study included 112 pregnant women (with and without SGA, n = 56 each). Maternal serum samples were collected at 10–...

The root bark of Morus alba L. has cytotoxic activity against several types of cancer cells. However, little is known about its chemopreventive mechanisms and bioactive metabolites. In this study, we showed that M. alba L. root bark extracts (MRBE) suppressed β-catenin response transcription (CRT), which is aberrantly activated in various cancers,...

Background: Abnormal maternal hypothalamus-pituitary-adrenal axis is associated with fetal growth, and we hypothesized that the alteration in metabolic signatures of cortisol might be detectable during early pregnancy. The objective of this study was to identify predictable maternal serum signatures of cortisol metabolism during the first trimester...

The precise determination of the chemical composition in crops is important to identify their nutritional and functional value. The current study performed a systematic delineation of the rice metabolome, an important staple in Asia, to investigate the following: (1) comparative features between brown and white rice; (2) variety-specific compositio...

With the increase in soybean trade between countries, the intentional mislabeling of the origin of soybeans has become a serious problem worldwide. In this study, metabolic profiling of soybeans from the Republic of Korea and China was performed by nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistical analysis to predi...

Most extremophilic anaerobes possess a sulfur formation (Suf) system for Fe–S cluster biogenesis. In addition to its essential role in redox chemistry and stress responses of Fe–S cluster proteins, the Suf system may play an important role in keratin degradation by Fervidobacterium islandicum AW‐1. Comparative genomics of the order Thermotogales re...

Early identification of patients at risk of developing preeclampsia (PE) would allow providers to tailor their prenatal management and adopt preventive strategies, such as low-dose aspirin. Nevertheless, no mid-trimester biomarkers have as yet been proven useful for prediction of PE. This study investigates the ability of metabolomic biomarkers in...

Sesame seeds are an oil crop mainly cultivated in Asian and African countries. Identification of the geographical origin of sesame seeds is an important issue for preventing adulteration and for quality assurance. This study was performed to establish a discrimination model and investigate potential biomarkers for differentiating the geographical o...

Nutrition-compositional evaluation is critical for quality control and value determination of agricultural products. Sesame seed is an important crop worldwide, enriched with primary nutrients and bioactive compounds. Here, we metabo-typed sesame seeds cultivated in Korea (N = 20) and imported from China (N = 11), South Asia (India and Pakistan), a...

Particulate matter (PM) exposure is related to an increased risk of sporadic Alzheimer's disease (AD), the pathogenesis of which is explained by chronic neurometabolic disturbance. Therefore, PM-induced alterations in neurometabolism might herald AD. We aimed to identify brain region-specific changes in metabolic pathways associated with ultrafine...

Fermentation has recently re-emerged as an approach for improved functionality of food products in addition to the traditional roles such as shelf life, taste, and texture. Here, we report dynamic changes in metabolite profiles of the Achyranthes japonica Nakai by Lactobacillus plantarum fermentation. Primarily, the significant increases in represe...

Bioconversion of lignocellulosic biomass into ethanol requires efficient xylose fermentation. Previously, we developed an engineered Saccharomyces cerevisiae strain, named SR8, through rational and inverse metabolic engineering strategies, thereby improving its xylose fermentation and ethanol production. However, its fermentation characteristics ha...

Internet Gaming Disorder (IGD) is characterized by uncontrollable and persistent playing of internet games despite the occurrence of negative consequences. Although there is a worldwide treatment demand, IGD still doesn't have an explicit biomarker. The primary goal of the study is to characterize lipidomic profiles specific to internet gaming diso...

The basis for region-specific neuronal toxicity in Huntington disease is unknown. Here, we show that region-specific neuronal vulnerability is a substrate-driven response in astrocytes. Glucose is low in HdhQ(150/150) animals, and astrocytes in each brain region adapt by metabolically reprogramming their mitochondria to use endogenous, non-glycolyt...

Classification and characterization of agricultural products at molecular levels are important but often impractical with genotyping, particularly for soybeans that have numerous types of variety and landraces. Alternatively, metabolic signature, a determinant for nutritional value, can be the good molecular indicator, which reflects cultivation re...

Guillain–Barré syndrome (GBS) is an acute fatal progressive disease caused by autoimmune mechanism mainly affecting peripheral nervous system. Although the syndrome is clinically sub-classified into several variants, specific biomarker and exact pathomechanism of each subtypes are not well elucidated yet. In current study, integrative metabolomic a...

In this study, an evolved Saccharomyces cerevisiae HJ7-14 with high ability of algae-based ethanol production was characterized by multi-omic approaches. Genome sequencing of the HJ7-14 revealed a point mutation in the GAL83 gene (G703A) involved in the catabolite repression as well as the galactose metabolism. Cultural and transcriptional analyses...

Graves' disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves' ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic...

Yeast with multiple tolerance onto harsh conditions has a number of advantages for bioethanol production. In this study, an alcohol yeast of Issatchenkia orientalis MTY1 was isolated in a Korean winery and its multiple tolerance against high temperature and acidic conditions was characterized in microaerobic batch cultures and by metabolomic analys...

The main aim of the current research is to characterize the molecular dynamics related to internet gaming disorder (IGD) using non-targeted plasma metabolite profiling based on gas-chromatography time-of-flight mass spectrometry (GC-TOF MS). IGD is a psychiatric disorder instigated by excessive and prolonged internet gaming, which shared many patho...

Central nervous system (CNS) inflammatory demyelinating diseases (IDDs) are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and idiopathic transverse myelitis (ITM). Differential diagnosis of the CNS IDDs still re...

Subject and sample characteristics by subject group. (TIF)

Principal component analysis of metabolomic profiles of CSF samples. Score scatter plots show no significant effect of therapeutic treatments regardless of IDDs types. (TIF)

ROC curves with the 95% confidence intervals using 500 bootstrappings. (TIF)

Shared-and-unique-structures (SUS) plots with the p(corr) values in the OPLS-DA model. The SUS plot analysis for the relative contribution of metabolite variables to the discriminant models of control versus remission (X-axis) and control versus relapse (Y-axis) in merged data set (control vs all disease). (TIF)

Optimal number of metabolites in the biomarker panel. The X-axis indicates the number of metabolites within the biomarker panel. To optimize this number, area under the curve (AUC) values were calculated using receiver operating characteristic (ROC) analysis, as depicted on the Y-axis. (TIF)

The goal of this study is to identify systematic biomarker panel for primary nephrotic syndromes from urine samples by applying a non-target metabolite profiling, and to validate their utility in independent sampling and analysis by multiplex statistical approaches. Nephrotic syndrome (NS) is a nonspecific kidney disorder, which is mostly represent...

The microalga-sourced bioactive metabolites are of particular interest related to new product strategy for medicinal, nutritional, cosmetic, and food industries. Conventional approach is to introduce physical stimuli such as pH and luminescence for the algal production. However, considering the specificity and effectiveness, it would be the best wa...

Transient receptor potential (TRP) cation channels are highly conserved in humans and insects. Some of these channels are expressed in internal organs and their functions remain incompletely understood. By direct knock-in of the GAL4 gene into the trpA1 locus in Drosophila, we identified the expression of this gene in the subesophageal ganglion (SO...

An essential question in cancer is why individuals with the same disease have different clinical outcomes. Progress toward a more personalized medicine in cancer patients requires taking into account the underlying heterogeneity at different molecular levels. Here, we present a model in which there are complex interactions at different cellular and...

Huntington's Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the e...

For the analysis of multiple-reaction intermediates for long-chain dicarboxylic acid biotransformation, simple and reproducible methods of extraction and derivatization were developed on the basis of gas chromatography with flame ionization detector (GC-FID) instead of mass spectrometer (MS). In the derivatization step, change of the ratio of pyrid...

Trinucleotide repeats (TNRs) expansion disorders are severe neurodegenerative and neuromuscular disorders that arise from inheriting a long tract (30–50 copies) of a trinucleotide unit within or near an expressed gene (Figure 1a). The mutation is referred to as ‘trinucleotide expansion’ since the number of triplet units in a mutated gene is greater...

Metabolomic results on human blood plasma largely depend on the sample preparation protocols employed for protein precipitation and metabolite extraction. Five different extraction methods were examined, which can be grouped into two categories, liquid-liquid extraction and protein precipitation methods, including long-standing protocols such as th...

Stress is now recognized as a universal premorbid factor associated with many risk factors of various chronic diseases. Acute stress may induce an individual's adaptive response to environmental demands. However, chronic, excessive stress causes cumulative, negatively impacts on health outcomes through "allostatic load". Thus monitoring of quantifi...

Loss of cholesterol homeostasis and altered vesicle trafficking have been detected in Huntington's disease (HD) cellular and animal models, yet the role of these dysfunctions in pathophysiology of HD is unknown. We demonstrate here that defects in caveolar-related cholesterol trafficking directly contribute to the mechanism of HD in vivo. We genera...

Many hereditary diseases are characterized by region-specific toxicity, despite the fact that disease-linked proteins are generally ubiquitously expressed. The underlying basis of the region-specific vulnerability remains enigmatic. Here, we evaluate the fundamental features of mitochondrial and glucose metabolism in synaptosomes from four brain re...

Simplified diagram of glycolysis and oxidative phosphorylation and inhibitors. Glycolysis converts glucose to cytosolic pyruvate, which is either converted to lactic acid or enters the mitochondrial matrix as a substrate for oxidative phosphorylation, measured as oxygen consumption rate (OCR, red). Rotenone, antimycin A, and oligomycin are the inhi...

Mass spectrometry data transformation. (A) The distribution of metabolite intensities after logarithmic normalization. (B) The distribution of metabolite intensities following quantile normalization. X and Y-axis indicate frequency and normalized abundances of metabolites respectively. (TIF)

Relative pool size of primary metabolites of the hippocampus region. The metabolic network shows relative abundance of primary metabolites of the cortex compared to those of other brain regions. Blue = down regulated metabolites, red = up regulated metabolites at 0%<median false discovery rate <0.5% from SAM (n = 5 or 6). Ball sizes reflect magnitu...

GC/MS profiles of TCA cycle intermediates. The abundance of TCA cycle intermediates among four different brain regions is measured using gas-chromatography mass spectrometry (GC/MS) (n = 5 or 6) (cerebellum: till, hippocampus: blue, striatum: red, cortex: light green). Data are displayed by box-whisker plots, giving the arithmetic mean for each cat...

Identification of metabolites with significant differences in abundance using Significance Analysis of Microarray. Scatter plot of the observed relative difference versus the expected relative difference. The solid line indicates the line for the condition, where the observed relative difference is identical to the expected relative difference. The...

Relative pool size of primary metabolites of the cortex region. The metabolic network shows relative abundance of primary metabolites of the cortex compared to those of other brain regions. Blue = down regulated metabolites, red = up regulated metabolites at a median false discovery rate <0.5% from SAM (n = 5 or 6). Ball sizes reflect magnitude of...

Contains: Table S1, S2, S3. (XLSX)

GC/MS profiles of glycolytic intermediates. The abundance of glycolytic intermediates among four different brain regions is measured using gas-chromatography mass spectrometry (GC/MS) (n = 5 or 6) (cerebellum: till, hippocampus: blue, striatum: red, cortex: light green). Data are displayed by box-whisker plots, giving the arithmetic mean for each c...

Relative pool size of primary metabolites of the striatum region. The metabolic network shows relative abundance of primary metabolites of the cortex compared to those of other brain regions. Blue = down regulated metabolites, red = up regulated metabolites at 0%<median false discovery rate <0.5% from SAM (n = 5 or 6). Ball sizes reflect magnitude...

Relative pool size of primary metabolites of the cerebellum region. The metabolic network shows relative abundance of primary metabolites of the cortex compared to those of other brain regions. Blue = down regulated metabolites, red = up regulated metabolites at 0%<median false discovery rate <0.5% from SAM (n = 5 or 6). Ball sizes reflect magnitud...

Current tandem mass spectral libraries for lipid annotations in metabolomics are limited in size and diversity. We provide a freely available computer-generated tandem mass spectral library of 212,516 spectra covering 119,200 compounds from 26 lipid compound classes, including phospholipids, glycerolipids, bacterial lipoglycans and plant glycolipid...

Many trinucleotide repeat disorders exhibit region-specific toxicity within tissues, the basis of which cannot be explained by traditional methods. For example, in Huntington's Disease (HD), the toxic disease-causing protein is ubiquitously expressed. However, only the medium spiny neurons in the striatum are initially targeted for death. Many chan...

Rapamycin, known as inhibitor of Target of Rapamycin (TOR), is an immunosuppressant drug used to prevent rejection in organ transplantation. Despite the close association of TOR signaling cascade with various scopes of metabolism, it has not been thoroughly investigated at the level of metabolome yet. In our current study, we applied mass spectrome...

Metabolome sampling is one of the most important factors that determine the quality of metabolomics data. The main steps in metabolite sample preparation include quenching and metabolite extraction. Quenching with 60% (v/v) cold methanol at -40°C has been most commonly used for Saccharomyces cerevisiae, and this method was recently modified as "lea...