Jeong Hwa Lee

Kyung Hee University, Sŏul, Seoul, South Korea

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Publications (31)86.25 Total impact

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    ABSTRACT: In this study, we investigated whether hepatitis B virus (HBV) causes the alteration of lipid metabolism and composition during acute infection and liver regeneration in a mouse model. The liver controls lipid biogenesis and bile acid homeostasis. Infection of HBV causes various liver diseases and impairs liver regeneration. As there are very few reports available in the literature on lipid alterations by HBV infection or HBV-mediated liver injury, we have analyzed phospholipids that have important roles in liver regeneration by using matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) in the livers of HBV model mice. As a result, we identified different phosphatidylcholines (PCs) showing significant changes in their composition as well as cationized ion adduct formation in HBV-infected mouse livers which are associated with virus-mediated regeneration defects. To find the factor of altered PCs, the expression kinetics of enzymes was also examined that regulate PC biosynthesis during liver regeneration. It is noteworthy that the expression of choline-phosphate cytidylyltransferase A (PCYT1A) was significantly delayed in wild type HBV-expressing livers. Moreover, the amount of hepatic total PC was also significantly decreased in wt HBV-expressing mice. These results suggest that infection of HBV alters the composition of PCs which may involve in HBV-mediated regeneration defects and liver disease.
    Full-text · Article · Aug 2014 · PLoS ONE
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    ABSTRACT: Tissue matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS)may identify lipids differentially expressed between cancer and adjacent normal tissue. To identify lipidomic profiles for gastric cancer, 24 gastric cancerswere profiled for lipid by the histology-directed, tissue MALDI MS technology. Lipid profiles differed between gastric cancer and adjacent normal tissue samples. At P<0.05, median class prediction accuracy in 100 random training-to-test partitions was 83.3% (5/6) for all classifiers tested. A peak at m/z 741.6 (sphingomyelin 34:1 K) was overexpressed, and a peak at m/z 782.6 (phosphatidylcholine 34:1 Na) was underexpressed in gastric cancers compared with normal tissue. Thus, lipid MALDI MS analysis may capture a global alteration in lipid profile of gastric cancer tissue, distinguishing cancerous epithelium from normal epithelium.
    Full-text · Article · Jul 2014 · The Open Proteomics Journal
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    ABSTRACT: Direct tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization and time-of-flight (MALDI-TOF) mass spectrometry has become increasingly important in biology and medicine, because this technology can detect the relative abundance and spatial distribution of interesting proteins in tissues. Five thyroid cancer samples, along with normal tissue, were sliced and transferred onto conductive glass slides. After laser scanning by MALDI-TOF equipped with a smart beam laser, images were created for individual masses and proteins were classified at 200-µm spatial resolution. Based on the spatial distribution, region-specific proteins on a tumor lesion could be identified by protein extraction from tumor tissue and analysis using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using all the spectral data at each spot, various intensities of a specific peak were detected in the tumor and normal regions of the thyroid. Differences in the molecular weights of expressed proteins between tumor and normal regions were analyzed using unsupervised and supervised clustering. To verify the presence of discovered proteins through IMS, we identified ribosomal protein P2, which is specific for cancer. We have demonstrated the feasibility of IMS as a useful tool for the analysis of tissue sections, and identified the tumor-specific protein ribosomal protein P2. Graphical Abstract
    Full-text · Article · Jul 2014 · Journal of Korean Medical Science
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    ABSTRACT: Histopathologic diagnosis of renal cell carcinoma (RCC) may sometimes be difficult with small biopsy samples. We applied histology-directed matrix-assisted laser desorption/ionization mass spectrometry to RCC samples to evaluate whether and how lipid profiles are different between RCC and normal tissue. We evaluated 59 RCC samples and 24 adjacent normal tissue samples collected from patients who underwent surgery. Five peaks were significantly differently expressed (p < 10(-7) ) between RCCs and adjacent normal tissue samples. C24-OH sulfatide (ST-OH {18:1/24:0}[M-H](-) ; m/z 906.7 in the negative ion mode) and C22-OH sulfatide (ST-OH {18:1/22:0}[M-H](-) ; m/z 878.6 in the negative ion mode) were most significantly underexpressed in RCC samples, compared with adjacent normal tissue samples. With 100 random training-to-test partitions within these samples, the median prediction accuracy (RCC vs. normal) ranged from 96.3% to 100% at p cutoff values for feature selection ranging from 0.001 to 10(-7) . Two oncocytoma samples were predicted as normal tissue by five lipids that were differentially expressed between RCC and normal tissue at p < 10(-7) . Clear-cell, papillary, and chromophobe RCCs were different in lipid profiles. Permutation p- values for 0.632+ bootstrap cross-validated misclassification rates were less than 0.05 for all the classifiers. Thus, lipid profiles differentiate RCC from normal tissue and may possibly classify the histology of RCC. © 2014 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons, Ltd.
    Full-text · Article · May 2014 · Journal of Mass Spectrometry
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    ABSTRACT: Microvesicles (MVs, also known as exosomes, ectosomes, microparticles) are released by various cancer cells, including lung, colorectal and prostate carcinoma cells. MVs released from tumor cells and other sources accumulate in the circulation and in pleural effusion (PE). Although recent studies have shown that MVs play multiple roles in tumor progression, the potential pathological roles of MV in pleural effusion, and their protein composition, are still unknown. In this study we report the first global proteomic analysis of highly purified MVs derived from human non-small-cell-lung-cancer (NSCLC) pleural effusion. Using nano-LC-MS/MS following 1-D SDS-PAGE separation, we identified a total of 912 MV proteins with high confidence. Three independent experiments on three patients showed that MV proteins from PE were distinct from MV obtained from other malignancies. Bioinformatics analyses of the MS data identified pathologically relevant proteins and potential diagnostic makers for NSCLC, including lung-enriched surface antigens and proteins related to EGFR signaling. These findings provide new insight into the diverse functions of MVs in cancer progression and will aid in the development of novel diagnostic tools for NSCLC.
    No preview · Article · Jul 2013 · Proteomics
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    ABSTRACT: Accumulating data indicate that human epidermal growth factor receptor-2 (HER2)-positive breast cancer is a heterogeneous disease. We undertook a study to correlate lipid profiles with heterogeneous clinicopathological features of HER2-positive breast cancer. Histology-directed matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS) analyses were performed on 22 retrospective frozen tissue samples collected from patients with HER2-positive metastatic breast cancer, in order to correlate lipid profiles with clinicopathological characterisitics. Additionally, a pair of tumor and adjacent normal tissue was profiled to identify cancer-associated changes in lipid profiles. Sphingomyelin 34:1, phosphatidylcholine (PC) 32:0, and PC 34:1, and PC 36:2 were overexpressed in HER2-positive breast cancer compared to adjacent normal tissue (HER2 signature). Lipid MALDI-MS profiles were different between Ki-67-high and Ki-67-low tumors. The proliferation signature (Ki-67-high vs. Ki-67-low) and the HER2 signature (cancer vs. normal) did not significantly overlap with each other. For the first time to our knowledge, this study describes lipid profiles correlated with various clinicopathological characteristics of HER2-positive breast cancer. Lipid profiling might be helpful for the molecular characterization of this disease.
    No preview · Article · Jun 2013 · Anticancer research
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    ABSTRACT: Objective: Blocking agents targeting cell adhesion molecules have been developed to prevent cardiovascular diseases such as atherosclerosis, whereas relatively little attention has been paid to the therapeutic potential of vascular cell adhesion molecule (VCAM)-1 as an inflammatory disease target. Two novel, fully human antibodies, H6 and 7H, against human VCAM-1 (hVCAM-1) were developed and tested to validate the hypothesis that blocking VCAM-1 ameliorates atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. Methods and results: Treatment with H6 or 7H effectively inhibited VCAM-1 adhesion to inflammatory cells, and reduced RhoA activation and the production of reactive oxygen species in human umbilical cord vascular endothelial cells. As 7H showed binding affinity to both murine VCAM-1 (mVCAM-1) and hVCAM-1, the therapeutic effects of 7H in ApoE(-/-) mice were tested. After confirming specific in vivo binding activity of 7H to mVCAM-1, we showed that administering 7H resulted in significantly ameliorated plaque formation compared to administering a control antibody in ApoE(-/-) mice fed a Western diet for 12 weeks. Also, 7H treatment significantly reduced infiltration of CD45(+) cells into plaques and reduced inflammation and improved plaque stability. Conclusion: These results indicate that the anti-VCAM-1 antibody attenuates atherosclerosis in ApoE(-/-) mice, improves plaque inflammation and stability as well as inhibiting the adhesion of inflammatory cell, and suggest that blocking VCAM-1 with a monoclonal antibody may be an effective means of anti-atherosclerotic therapy.
    No preview · Article · Dec 2012 · Atherosclerosis
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    ABSTRACT: Since the development of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, this procedure has been specifically used for analyzing proteins or high molecular weight compounds because of the interference of matrix signals in the regions of the low mass range. Recently, scientists have been using a wide range of chemical compounds as matrices that ionize small molecules in a mass spectrometer and overcome the limitations of MALDI mass spectrometry. In this study, we developed a new combination matrix of 3-hydroxycoumarin (3-HC) and 6-aza-2-thiothymine (ATT), which is capable of ionizing small molecules, including drugs and single amino acids. In addition to ionization of small molecules, the combination matrix by itself gives less signals in the low mass region and can be used for performing imaging mass spectrometry (IMS) experiments on tissues, which confirms the vacuum stability of the matrix inside a MALDI chamber. The drug donepezil was mapped in the intact tissue slices of mice simultaneously with a spatial resolution of 150 μm during IMS. IMS analysis clearly showed that intact donepezil was concentrated in the cortical region of the brain at 60 min after oral administration. Our observations and results indicate that the new combination matrix can be used for analyzing small molecules in complex samples using MALDI mass spectrometry.
    Full-text · Article · Oct 2012 · The Analyst
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    ABSTRACT: Neuronal membrane phospholipids are highly affected by oxidative stress caused by ischemic injury. Thus, it is necessary to identify key lipid components that show changes during ischemia to develop an effective approach to prevent brain damage from ischemic injury. The recent development of MALDI imaging MS (MALDI IMS) makes it possible to identify phospholipids that change between damaged and normal regions directly from tissues. In this study, we conducted IMS on rat brains damaged by ischemic injury and detected various phospholipids that showed unique distributions between normal and damaged areas of the brain. Among them, we confirmed changes in phospholipids such as lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin by MALDI IMS followed by MS/MS analysis. These lipids were present in high concentrations in the brain and are important for maintenance of cellular structure as well as production of second messengers for cellular signal transduction. Our results emphasize the identification of phospholipid markers for ischemic injury and successfully identified several distinctly located phospholipids in ischemic brain tissue.
    Full-text · Article · Jun 2012 · The Journal of Lipid Research
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    ABSTRACT: Pancreatic pseudocysts occur following acute pancreatitis, chronic pancreatitis or secondary to pancreatic trauma. Most pancreatic pseudocysts are located in or around the pancreas, but they can be found in all the potential spaces around viscera in and outside of the abdominal cavity. The complications of pancreatic pseudocyst are infection, rupture, obstruction, fistula, or hemorrhage. Hemorrhage is a rare but frequently fatal complication of pancreatic pseudocysts. We report a case of pancreatic pseudocyst presented as bleeding of duodenum, which was misidentified for duodenal submucosal tumor bleeding.
    No preview · Article · Jan 2012
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    ABSTRACT: We investigated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis on lipid may assist with the histopathologic diagnosis of non-small cell lung cancers (NSCLCs). Twenty-one pairs of frozen, resected NSCLCs and adjacent normal tissue samples were initially analyzed using histology-directed, MALDI MS. 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. A lipid profile that could differentiate cancer and adjacent normal samples with a median accuracy of 92.9% was discovered. Several phospholipids including phosphatidylcholines (PC) {34:1} were overexpressed in lung cancer. Squamous cell carcinomas and adenocarcinomas were found to have different lipid profiles. Discriminatory lipids correctly classified the histology of 80.4% of independent NSCLC surgical tissue samples (41 out of 51) in validation set. MALDI MS image of 11 discriminatory lipids validated their differential expression according to the histologic type in cancer cells of bronchoscopic biopsy samples. PC {32:0} [M+Na](+) (m/z 756.68) and ST-OH {42:1} [M-H](-) (m/z 906.89) were overexpressed in adenocarcinomas. Thus, lipid profiles accurately distinguish tumor from adjacent normal tissue and classify non-small cell lung cancers according to the histologic type.
    No preview · Article · Nov 2011 · Lung cancer (Amsterdam, Netherlands)
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    ABSTRACT: Procedures for MALDI MS analysis. A representative cancer tissue cryosection, with the DHB/CHCA matrix applied at the locations marked in the H&E section, is shown at the bottom. The H&E section marked at discrete locations (enriched in tumor cells) using a red color marker pen (center) and magnified (× 20) areas of the H&E-stained section corresponding to matrix-loaded spots (top left and right) are shown at the top.
    Preview · Dataset · Oct 2011
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    ABSTRACT: Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) has been demonstrated to be useful for molecular profiling of common solid tumors. Using recently developed MALDI matrices for lipid profiling, we evaluated whether direct tissue MALDI MS analysis on proteins and lipids may classify human breast cancer samples according to the intrinsic subtype. Thirty-four pairs of frozen, resected breast cancer and adjacent normal tissue samples were analyzed using histology-directed, MALDI MS analysis. Sinapinic acid and 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. Protein and lipid profiles distinguish cancer from adjacent normal tissue samples with the median prediction accuracy of 94.1%. Luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by permutation P values less than 0.01 for 0.632+ bootstrap cross-validated misclassification rates with all classifiers tested. Discriminatory proteins and lipids were useful for classifying tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in random test sets. Protein and lipid profiles accurately distinguish tumor from adjacent normal tissue and classify breast cancers according to the intrinsic subtype.
    Full-text · Article · Oct 2011 · BMC Cancer
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    ABSTRACT: Peroxiredoxin 2 (Prdx2), a thiol-specific peroxidase, has been reported to regulate proinflammatory responses, vascular remodeling, and global oxidative stress. Although Prdx2 has been proposed to retard atherosclerosis development, no direct evidence and mechanisms have been reported. We show that Prdx2 is highly expressed in endothelial and immune cells in atherosclerotic lesions and blocked the increase of endogenous H(2)O(2) by atherogenic stimulation. Deficiency of Prdx2 in apolipoprotein E-deficient (ApoE(-/-)) mice accelerated plaque formation with enhanced activation of p65, c-Jun, JNKs, and p38 mitogen-activated protein kinase; and these proatherogenic effects of Prdx2 deficiency were rescued by administration of the antioxidant ebselen. In bone marrow transplantation experiments, we found that Prdx2 has a major role in inhibiting atherogenic responses in both vascular and immune cells. Prdx2 deficiency resulted in increased expression of vascular adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemotactic protein-1, which led to increased immune cell adhesion and infiltration into the aortic intima. Compared with deficiency of glutathione peroxidase 1 or catalase, Prdx2 deficiency showed a severe predisposition to develop atherosclerosis. Prdx2 is a specific peroxidase that inhibits atherogenic responses in vascular and inflammatory cells, and specific activation of Prdx2 may be an effective means of antiatherogenic therapy.
    Preview · Article · Aug 2011 · Circulation Research
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    ABSTRACT: Mesenchymal stem cells (MSCs) are multipotent cells, which have the capability to differentiate into various mesenchymal tissues such as bone, cartilage, fat, tendon, muscle, and marrow stroma. However, they lose the capability of multi-lineage differentiation after several passages. It is known that basic fibroblast growth factor (bFGF) increases growth rate, differentiation potential, and morphological changes of MSCs in vitro. In this report, we have used 2-DE coupled to MS to identify differentially expressed proteins at the cell membrane level in MSCs growing in bFGF containing medium. The cell surface proteins isolated by the biotin-avidin affinity column were separated by 2-DE in triplicate experiments. A total of 15 differentially expressed proteins were identified by quadrupole-time of flight tandem MS. Nine of the proteins were upregulated and six proteins were downregulated in the MSCs cultured with bFGF containing medium. The expression level of three actin-related proteins, F-actin-capping protein subunit alpha-1, actin-related protein 2/3 complex subunit 2, and myosin regulatory light chain 2, was confirmed by Western blot analysis. The results indicate that the expression levels of F-actin-capping protein subunit alpha-1, actin-related protein 2/3 complex subunit 2, and myosin regulatory light chain 2 are important in bFGF-induced morphological change of MSCs.
    No preview · Article · Sep 2009 · Proteomics
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    ABSTRACT: When we treated rat bone marrow stromal cells (rBMSCs) with neuronal differentiation induction media, typical unfolded protein response (UPR) was observed. BIP/GRP78 protein expression was time-dependently increased, and three branches of UPR were all activated. ATF6 increased the transcription of XBP1 which was successfully spliced by IRE1. PERK was phosphorylated and it was followed by eIF2alpha phosphorylation. Transcription of two downstream targets of eIF2alpha, ATF4 and CHOP/GADD153, were transiently up-regulated with the peak level at 24 h. Immunocytochemical study showed clear coexpression of BIP and ATF4 with NeuN and Map2, respectively. UPR was also observed during the neuronal differentiation of mouse embryonic stem (mES) cells. Finally, chemical endoplasmic reticulum (ER) stress inducers, thapsigargin, tunicamycin, and brefeldin A, dose-dependently increased both mRNA and protein expressions of NF-L, and, its expression was specific to BIP-positive rBMSCs. Our results showing the induction of UPR during neuronal differentiations of rBMSCs and mES cells as well as NF-L expression by ER stress inducers strongly suggest the potential role of UPR in neuronal differentiation.
    Full-text · Article · Apr 2009 · Experimental and Molecular Medicine
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    ABSTRACT: Pilus-mediated motility is essential for the optimization of photosynthesis and environmental adaptation in the cyanobacterium Synechocystis sp. PCC 6803 (Syn6803). To identify the genes required for pilus-mediated motility in Syn6803, we applied a forward genetic approach using a Tn5 mutant library and reverse genetics using interposon mutagenesis. One of the identified genes, sll0899, bears sequence similarity to acyltransferases and nucleotidyltransferases. The sll0899 gene product is not involved in the transcription or translation of pilA1, which encodes pilin, the major component of pili. Instead, the sll0899::Cm(r) mutant produced pilins with increased molecular mass, suggesting the existence of different PTMs. Using MS, we found that the wild-type (WT) and mutant pilins were glycosylated between amino acids 67 and 75. Analyses by quantitative MS and high-pH anion exchange chromatography (HPAEC) revealed that the glycan in WT pilin is composed of xylose and fucose, whereas an additional sugar, rhamnose, was found in the glycan of sll0899::Cm(r). Our findings suggest that an alteration in the O-linked glycan of pilin is responsible for the loss of pilus-mediated motility in sll0899::Cm(r).
    No preview · Article · Feb 2009 · Proteomics
  • Gun-Woo Kim · Jeong Hwa Lee · Jin Hyun Son
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    ABSTRACT: Business Process may have unexpected design anomalies in modeling phase. If business process engine executed without anomalies detection, the inappropriate progress will be executed and that will be lead to massive loss of costs and human capitals in organization. To ensure that there is no design anomalies in business process modeling phase and to detect anomalies of predefined actions within modeling tools are important issues in business process management. In this paper, we provide classification and analyses of business process anomalies, which can effectively use to detect or verification in business process modeling phase.
    No preview · Article · Jan 2009
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    ABSTRACT: Recently it was shown that single nucleotide polymorphisms (SNPs) can explain individual variation because of the small changes of the gene expression level and that the 50% decreased expression of an allele might even lead to predisposition to cancer. In this study, we found that a decreased expression of an allele might cause predisposition to genetic disease. Dopa responsive dystonia (DRD) is a dominant disease caused by mutations in GCH1 gene. The sequence analysis of the GCH1 in a patient with typical DRD symptoms revealed two novel missense mutations instead of a single dominant mutation. Family members with either of the mutations did not have any symptoms of DRD. The expression level of a R198W mutant allele decreased to about 50%, suggesting that modestly decreased expression caused by an SNP should lead to predisposition of a genetic disease in susceptible individuals.
    Preview · Article · Jul 2008 · Experimental and Molecular Medicine
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    ABSTRACT: We investigated the in vitro effect of modified Je-Ho-Tang (MJHT) hot-water extract on platelet aggregation and activation induced by agonists in human whole blood, and on platelet adhesion to a collagen-coated surface under flow shear stress conditions. MJHT extract potently inhibited the collagen-induced platelet aggregation in human whole blood in a dose-dependent manner, with a half-maximal inhibitory dose (IC(50)) value of 526 microg/mL. We accessed several markers of platelet activation using receptor expression on platelet membranes, including GPIIb/IIIa-like expression (PAC-1) and P-selectin (CD62); we monitored the intracellular calcium mobilization response by flow cytometry in healthy subjects. A significant decrease in PAC-1 (P=0.002), CD62 (P=0.002), and intracellular calcium mobilization (P<0.001) were seen in the presence of MJHT extract. In addition, we have used image analysis to study human platelet adhesion to collagen under physiologic flow conditions in a perfusion chamber. MJHT extract markedly decreased platelet adhesion to the collagen-coated surface. These results show that MJHT has potent anti-platelet activity.
    No preview · Article · May 2008 · Thrombosis Research

Publication Stats

386 Citations
86.25 Total Impact Points

Institutions

  • 2014
    • Kyung Hee University
      • Department of Applied Chemistry
      Sŏul, Seoul, South Korea
  • 2011-2014
    • Konkuk University
      • • Department of Internal medicine
      • • School of Medicine
      Sŏul, Seoul, South Korea
  • 2011-2012
    • Ewha Womans University
      • Department of Life Sciences
      Sŏul, Seoul, South Korea
  • 2006-2012
    • Catholic University of Korea
      • • Department of Internal Medicine
      • • College of Medicine
      Sŏul, Seoul, South Korea
  • 2009
    • Hanyang University
      • Department of Computer Science and Engineering
      Sŏul, Seoul, South Korea
  • 2008
    • Korea Institute of Oriental Medicine
      Bucheon, Gyeonggi-do, South Korea
    • National Cancer Center Korea
      Kōyō, Gyeonggi Province, South Korea
  • 2003-2008
    • Korea Basic Science Institute KBSI
      • Division of Magnetic Resonance Research
      Sŏul, Seoul, South Korea