Eun Hee Kim

Korea Basic Science Institute KBSI, Sŏul, Seoul, South Korea

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Publications (122)301.11 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective The degree of subclinical coronary atherosclerosis detected by coronary multidetector computed tomography (MDCT) in four groups defined by the state of metabolic health and obesity in an asymptomatic Korean population was compared.Methods The data of 4009 asymptomatic subjects who participated in a routine health screening examination were collected. Significant coronary artery stenosis defined as >50% stenosis, plaque, and coronary artery calcium scores (CACS) were assessed by MDCT. Participants were stratified by BMI (cut-off value, 25 kg/m2) and metabolically healthy state, which was defined by Wildman criteria.ResultsMHO subjects had a significantly higher prevalence of significant subclinical coronary atherosclerotic burden compared with metabolically healthy nonobese (MHNO) subjects. The adjusted odds ratios of the MHO group for various coronary MDCT findings (MHNO group as the reference), such as coronary artery stenosis, any plaque, calcified plaque, mixed plaque, CACS > 0, and CACS > 100, were 1.87 (95% CI 1.15-3.03), 1.31 (1.01-1.71), 1.40 (1.05-1.86), 1.57 (1.01-2.48), 1.38 (1.04-1.82), and 1.69 (1.03-2.78), respectively.Conclusions Our data illustrate that MHO subjects have substantial subclinical coronary atherosclerotic burden. Thus, it is important to consider the metabolic health state and obesity in evaluating cardiovascular risk.
    Obesity 08/2014; · 3.92 Impact Factor
  • Angewandte Chemie 07/2014;
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    ABSTRACT: Aptides, a novel class of high-affinity peptides, recognize diverse molecular targets with high affinity and specificity. The solution structure of the aptide APT specifically bound to fibronectin extradomain B (EDB), which represents an unusual protein–protein interaction that involves coupled unfolding and binding, is reported. APT binding is accompanied by unfolding of the C-terminal β strand of EDB, thereby permitting APT to interact with the freshly exposed hydrophobic interior surfaces of EDB. The β-hairpin scaffold of APT drives the interaction by a β-strand displacement mechanism, such that an intramolecular β sheet is replaced by an intermolecular β sheet. The unfolding of EDB perturbs the tight domain association between EDB and FN8 of fibronectin, thus highlighting its potential use as a scaffold that switches between stretched and bent conformations.
    Angewandte Chemie 07/2014;
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    ABSTRACT: This retrospective cohort study aimed to estimate the mean sojourn time (MST) of preclinical gastric cancer in Korean men.
    07/2014; 47(4):201-5.
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    ABSTRACT: Scutellaria baicalensis Georgi. (S. baicalensis G.), commonly known as skullcaps, and it has been widely used as traditional therapeutic herb in several eastern Asia including Korea, China and Japan because of its remarkable anti-inflammatory and anti-cancer effects.
    Journal of ethnopharmacology. 06/2014;
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    ABSTRACT: Cyclosporine is an immunosuppressant drug used in organ transplants or for the treatment of autoimmune diseases. We developed and validated a simple, sensitive, and specific method using UPLC-MS/MS to determine cyclosporine levels in human whole blood. MS/MS detection was performed in the positive electrospray ionization mode with multiple reaction monitoring. Cyclosporine was extracted from whole-blood samples using ascomycin as an internal standard. The mass transitions m/z 1203.49 → 1185.53 and m/z 814.71 → 796.67 were used to assay the analyte and IS. This method was validated with respect to linearity, specificity, accuracy, precision, recovery, and stability. The method exhibited a linear response from 10 to 1000 ng mL(-1) with correlation coefficient values >0.99. The precision and the accuracy values were within 15%, except at the lower limit of quatification (LLOQ). Cyclosporine was stable in whole blood with no evidence of degradation. This method was successfully applied to a pharmacokinetic study of cyclosporine in healthy volunteers following oral administration.
    Analytical Sciences 01/2014; 30(2):293-8. · 1.57 Impact Factor
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    ABSTRACT: The repair process after CNS injury shows a well-organized cascade of three distinct stages: inflammation, new tissue formation, and remodeling. In the new tissue formation stage, various cells migrate and form the fibrotic scar surrounding the lesion site. The fibrotic scar is known as an obstacle for axonal regeneration in the remodeling stage. However, the role of the fibrotic scar in the new tissue formation stage remains largely unknown. We found that the number of A-kinase anchoring protein 12 (AKAP12)-positive cells in the fibrotic scar was increased over time, and the cells formed a structure which traps various immune cells. Furthermore, the AKAP12-positive cells strongly express junction proteins which enable the structure to function as a physical barrier. In in vivo validation, AKAP12 knock-out (KO) mice showed leakage from a lesion, resulting from an impaired structure with the loss of the junction complex. Consistently, focal brain injury in the AKAP12 KO mice led to extended inflammation and more severe tissue damage compared to the wild type (WT) mice. Accordingly, our results suggest that AKAP12-positive cells in the fibrotic scar may restrict excessive inflammation, demonstrating certain mechanisms that could underlie the beneficial actions of the fibrotic scar in the new tissue formation stage during the CNS repair process.
    PLoS ONE 01/2014; 9(4):e94695. · 3.73 Impact Factor
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    ABSTRACT: Hesperidin, a natural flavonoid abundantly present in Citrus is known for its anti-cancer, anti-oxidant and anti-inflammatory properties. In this study we examined the effect of hesperidin on HepG2 cells. HepG2 cells treated with various concentration of hesperidin undergo a distinct type of programed cell death. Cytoplasmic vacuolization, mitochondria and endoplasmic reticulum swelling and uncondensed chromatin were observed in hesperidin treated cells. DNA electrophoresis show lack of DNA fragmentation and western blot analysis demonstrates lack of caspase activation and PARP cleavage. It was observed that hesperidin induced cell death is nonautophagic and also activate mitogen activated protein kinase ERK1/2. Taken together, the data indicate that hesperidin induces paraptosis like cell death in HepG2 cells with the activation of ERK1/2. Thus our finding suggests that hesperidin inducing paraptosis may offer an alternative tool in human liver carcinoma therapy.
    PLoS ONE 01/2014; 9(6):e101321. · 3.73 Impact Factor
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    ABSTRACT: Aims/IntroductionInsulin has been associated with the risk of colorectal cancer (CRC). However, few studies have evaluated the association between insulin and colorectal adenoma. We investigated the relationship between fasting serum insulin levels or homeostasis model assessment of insulin resistance (HOMA-IR) and colorectal adenoma. Materials and Methods We retrospectively enrolled 15,427 participants who underwent both fasting serum insulin measurement and colonoscopy for a routine health examination at Asan Medical Center from January 2007 to December 2008. Participants with a history of any cancer, previous colectomy or polypectomy, those taking antidiabetic medications, and inflammatory bowel disease, non-specific colitis, non-adenomatous polyps only or CRC on colonoscopic findings were excluded. Finally, 3,606 participants with histologically confirmed colorectal adenoma and 6,019 controls with no abnormal findings on colonoscopy were included. Participants were categorized into quartiles (Q) based on fasting serum insulin levels and HOMA-IR. ResultsFasting serum insulin and HOMA-IR were significantly higher in participants with colorectal adenomas compared with controls. Multivariate regression analysis adjusting for age, sex, smoking habits, drinking habits and family history of CRC showed that participants with higher quartiles of fasting serum insulin levels (odd ratio [OR] 1.17 for 2nd Q, 1.19 for 3rd Q, and 1.42 for 4th Q, P < 0.05) or HOMA-IR (OR 1.18 for 2nd Q and 1.45 for 4th Q, P < 0.05) showed significantly increased ORs of colorectal adenoma compared with the lowest quartiles. Conclusions These findings showed that increased serum insulin levels and insulin resistance were significantly associated with the presence of colorectal adenoma.
    Journal of Diabetes Investigation. 12/2013;
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    ABSTRACT: Vitamin C (ascorbic acid) is an essential nutrient of most living tissues that readily acts as a strong reducing agent, which is abundant in fruits and vegetables. Although, it inhibits cell growth in many human cancer cells in vitro, treatment in cancer is still controversial. Hence, the purpose of this study was to investigate the molecular mechanism of the inhibitory effect of vitamin C on AGS cell growth, and protein profiles in AGS cells after exposure to vitamin C treatment, by using proteomic tools. Vitamin C showed a cytotoxic effect on AGS cells (IC50 300mug/mL) and, 20 differentially expressed proteins (spot intensities which show >=2 fold change and statistically significant, p<0.05 between the control and vitamin-C treated group) were successfully identified by assisted laser desorption/ ionization-time of flight/mass spectrometry (MALDI-TOF/MS). Of the 20 proteins, six were up-regulated and fourteen were down-regulated. Specifically, 14-3-3sigma, 14-3-3epsilon, 14-3-3delta, tropomyosin alpha-3 chain and tropomyosin alpha-4 chain were down-regulated and peroxiredoxin-4 and thioredoxin domain-containing proteins 5 were up-regulated. The identified proteins are mainly involved in cell mobility, antioxidant and detoxification, signal transduction and protein metabolism. Further, the expressions of 14-3-3 isoforms were verified with immuno-blotting analysis. Our proteome results suggest that the apoptosis related proteins were involved in promoting and regulating cell death of AGS cells, and might be helpful to understand the molecular mechanism of vitamin C on AGS cell growth inhibition.
    BMC Biochemistry 09/2013; 14(1):24. · 1.78 Impact Factor
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    ABSTRACT: The authors identified risk factors for acute kidney injury (AKI) defined by risk, injury, failure, loss, end-stage (RIFLE) criteria after aortic surgery with cardiopulmonary bypass and constructed a simplified risk score for the prediction of AKI. Retrospective and observational. Single large university hospital. Patients (737) who underwent aortic surgery with cardiopulmonary bypass between 1997 and 2010. Multivariate logistic regression analysis was used to evaluate risk factors. A scoring model was developed in a randomly selected derivation cohort (n = 417), and was validated on the remaining patients. The scoring model was developed with a score based on regression β-coefficient, and was compared with previous indices as measured by the area under the receiver operating characteristic curve (AUC). The incidence of AKI was 29.0%, and 5.8% required renal replacement therapy. Independent risk factors for AKI were age older than 60 years, preoperative glomerular filtration rate <60 mL/min/1.73 m(2), left ventricular ejection fraction <55%, operation time >7 hours, intraoperative urine output <0.5 mL/kg/h, and intraoperative furosemide use. The authors made a score by weighting them at 1 point each. The risk score was valid in predicting AKI, and the AUC was 0.74 [95% confidence interval (CI): 0.69 to 0.79], which was similar to that in the validation cohort: 0.74 (95% CI: 0.69 to 0.80; p = 0.97). The risk-scoring model showed a better performance compared with previously reported indices. The model would provide a simplified clinical score stratifying the risk of postoperative AKI in patients undergoing aortic surgery.
    Journal of cardiothoracic and vascular anesthesia 09/2013; · 1.06 Impact Factor
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    ABSTRACT: Unlike most other mammals, human bodies do not have the ability to synthesize vitamin C inside of their own bodies. Therefore, humans must obtain vitamin C through daily diet. Gulo(-/-) mice strain is known with deficiency, in which vitamin C intake can be controlled by diet like human, and would be valuable for investigating the molecular mechanism of various diseases. In the present study, we established Gulo(-/-) mice model and investigated the differentially expressed proteins in stomach tissue of Gulo(-/-) mice after Helicobacter pylori-infected, and followed by DENA, using immunohistochemistry and proteomic approach. The results of immunohistochemistry analysis of stomach tissue showed that the tumor suppressor, p53 protein, expression was significantly decreased (p<0.05) but not messenger RNA (mRNA) transcriptional level, and 14-3-3ε, 14-3-3δ, Ki-67 and cleaved caspase 3 expressions were significantly increased (p<0.05) by H. Pylori infection, and followed by DENA treatment in Gulo(-/-) mice. Moreover, knockdown of 14-3-3 isoforms (14-3-3 ε, 14-3-3 σ, 14-3-3 ζ and 14-3-3 η) were significantly increased sub-G1 phase (characteristics of apoptosis) in AGS cells and, phenotypic changes like cell shrinkage, density and cleaved nuclei were also observed. Proteome analyses showed that 14-3-3σ, 14-3-3η, and tropomyosin alpha-1 chain were down-regulated, and Hspd1 protein and HSC70 were up-regulated after H. Pylori-infection, and followed by DENA. The combined results of immunohistochemistry and proteomic analysis suggest that H.pylori altered the p53 and 14-3-3 isoforms expression and DENA further enhanced the H.pylori effect, which might be involved in carcinogenesis and metastasis of gastric cancer on Gulo(-/-) mice.
    Chemico-biological interactions 09/2013; · 2.46 Impact Factor
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    ABSTRACT: The purpose of this study was to quantify the intelligence of children with epilepsy and to determine the clinical factors associated with intellectual impairment. The medical records of patients diagnosed with childhood-onset epilepsy at a single tertiary medical center in Korea between 2006 and 2011 were retrospectively reviewed. The Korean Education Development Institute-Wechsler Intelligence Scale for Children or Korean Wechsler Intelligence Scale for adults was used to quantify the level of intelligence. Age at seizure onset, etiology, epilepsy duration, number of seizures in the last year, use of antiepileptic drugs, EEG/MRI findings, and epilepsy classification were recorded. The association between clinical factors and the intelligence was determined using logistic regression. Three hundred and twenty-two patients were included in the analysis. One hundred and seventy-six (54.7%) patients had low intelligence (intelligence quotient [IQ]<80) with 18 (5.6%) defined as borderline mental retardation (IQ 70-79), 47 (14.6%) as mild mental retardation (IQ 60-69), and 111 (34.5%) as moderate-to-severe mental retardation (IQ<60). Epilepsy duration, number of seizures in the last year, and epilepsy classification were significantly associated with low intelligence in multivariate logistic regression (p<0.05). However, when analyzed according to etiology, these factors were not associated with low intelligence in children with idiopathic epilepsy. The most important factors associated with low intelligence in childhood-onset epilepsy are the underlying etiology and, in cryptogenic and symptomatic epilepsy, seizure burden. The results of this study underscore the importance of seizure control to alleviate the harmful impact of epilepsy on cognition.
    Epilepsy & Behavior 08/2013; 29(1):166-171. · 1.84 Impact Factor
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    ABSTRACT: Sirtuin 6 (SIRT6) belongs to the sirtuin family of NAD(+)-dependent deacetylases and has been implicated in the regulation of metabolism, inflammation, and aging. Here we found that SIRT6 was predominantly expressed in neuronal cells throughout the entire brain. Ischemia models using transient middle cerebral artery occlusion in rats and oxygen/glucose deprivation (OGD) in SH-SY5Y neuronal cells showed that ischemia reduced SIRT6 expression and induced the release of high mobility group box-1 (HMGB1) from cell nuclei. The reduced expression of SIRT6 via treatment with SIRT6 siRNA dramatically enhanced the OGD-induced release of HMGB1 in SH-SY5Y cells. Together, our data suggest that SIRT6 may serve as a potential therapeutic target for HMGB1-mediated inflammation after cerebral ischemia.
    Biochemical and Biophysical Research Communications 07/2013; · 2.41 Impact Factor
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    ABSTRACT: In this study, pharmacophore and 3D-QSAR models were developed for analogues of 3-substituted-benzofuran-2-carboxylate as inhibitors of Fas-mediated cell death pathways. Our pharmacophore model has good correspondence with experimental results and can explain the variance in biological activities coherently with respect to the structure of the data set compounds. The predictive power for our synthesized compounds were 0.96 for the pharmacophore model, 0.58 for the comparative molecular field analysis (CoMFA) model, and 0.57 for the comparative molecular similarity analysis (CoMSIA) model.
    Bioorganic & medicinal chemistry letters 07/2013; · 2.65 Impact Factor
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    ABSTRACT: Laser lipolysis has a skin tightening effect by heating the deep dermis, in addition to the removal of fat tissues. The 1444-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has been expected to be more effective and safe for laser lipolysis, due to higher affinity to fat and water, than 1064-nm and 1320-nm wavelengths. The purpose of this study was to evaluate the skin tightening effect of the 1444-nm Nd:YAG laser through in vivo guinea pig models. The 1444-nm Nd:YAG laser was used to irradiate shaved dorsal skin of the guinea pigs and compared with controls (no power, only tunneling). Immediately, 1 week, 1 month and 3 months after laser administration, full-thickness skins were harvested and to evaluate dermal thickness, collagen organization, fibroblast proliferation, and intensity of elastic fibers and mucopolysaccharides, using hematoxylin-eosin, Masson-trichrome, Verhoeff's stain and Alcian blue stain. Dermal thickness showed an increase with time in all groups. In collagen organization, fibroblast proliferation, and intensity of elastic fibers and mucopolysaccharides, the treatment groups were higher than those of the control group, overall. Our study showed that the 1444-nm Nd:YAG laser appeared to be effective for the skin tightening effect in in vivo guinea pig models. The 1444-nm Nd:YAG laser can be used for skin tightening, as well as reduction of fat tissues.
    The Journal of Dermatology 07/2013; · 1.77 Impact Factor
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    ABSTRACT: OBJECTIVES: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and suggested as a marker of atherosclerosis. We investigated whether plasma OPG levels were associated with the presence and severity of cerebral atherosclerosis. DESIGN AND METHODS: We used an enzyme-linked immunosorbent assay to measure the plasma OPG levels of 107 patients with acute cerebral infarction. We compared the plasma OPG levels according to the presence and number of arteries with cerebral atherosclerosis (≥ 50% stenosis). RESULTS: Of 107 patients, 73 (68.2 %) had cerebral atherosclerosis. OPG levels were increased in patients with cerebral atherosclerosis (374.69 ± 206.48 vs 261.17 ± 166.91 pg/mL, p=0.006). OPG levels showed positive correlation with the number of cerebral arteries with atherosclerosis (Spearman's rho=0.342, p<0.001). After adjustment for vascular risk factors, OPG > 229.9 pg/mL was independently associated with the presence [OR 4.61, 95% CI 1.57-13.55, p=0.005, binary logistic regression] of cerebral atherosclerosis and number [OR 3.20, 95% CI 1.26-8.12, p=0.014, ordinal logistic regression] of arteries with cerebral atherosclerosis. CONCLUSIONS: Plasma OPG levels were significantly associated with presence and severity of cerebral atherosclerosis. This finding suggests that plasma OPG might have a role in cerebral atherosclerosis.
    Clinical biochemistry 05/2013; · 2.02 Impact Factor
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    ABSTRACT: Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT), its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1 increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT.
    Journal of Korean medical science 05/2013; 28(5):709-16. · 0.84 Impact Factor
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    ABSTRACT: In this study, we investigated the efficacy and safety of the recently developed modifiable bioabsorbable plates and screws, which are made of PLGA [poly(lactic-co-glycolic acids)]. An in vitro extract test and a mammalian erythrocyte micronucleus test revealed that neither cytotoxicity nor genotoxicity was observed with the plates and screws tested in this study. An in vivo mandible fracture model in rabbit was introduced to evaluate the in vivo efficacy and of the PLGA-based plates and screws. At 4, 6, 8, and 10 weeks after implantation, tissue specimens were taken from the implanted sites of the rabbits and a histologic analysis was performed for each of the specimens. After 4 weeks, the plate was covered by connective tissues and severe chronic active inflammation in soft tissue was observed. After 6 weeks, the inflammation decreased and some of the specimens exhibited new bone formation around the periosteum. After 8 and 10 weeks, new bone formation was observed with all samples, where almost no severe inflammation was involved, implying the healing of the fracture. Given these, it can be suggested that the biodegradable plate and screw system that we evaluated in this study is effective for treatment of mandible fracture, one of the regions under a high load-bearing condition. The adjustment process and the long-term follow-up study are in progress for clinical application of the plate and screw system introduced in this study.
    The Journal of craniofacial surgery 05/2013; 24(3):1021-1025. · 0.81 Impact Factor
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    ABSTRACT: Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is preferentially cytotoxic to cancer cells over normal cells. However, many cancer cells, including malignant glioma cells, tend to be resistant to TRAIL. Monensin (a polyether ionophore antibiotic that is widely used in veterinary medicine) and salinomycin (a compound that is structurally related to monensin and shows cancer stem cell-inhibiting activity) are currently recognized as anticancer drug candidates. In the present study, we show that monensin effectively sensitizes various glioma cells, but not normal astrocytes, to TRAIL-mediated apoptosis; this occurs at least partly via monensin-induced endoplasmic reticulum (ER) stress, CHOP-mediated DR5 upregulation, and proteasome-mediated downregulation of c-FLIP. Interestingly, other polyether antibiotics, such as salinomycin, nigericin, narasin, and lasalocid A, also stimulated TRAIL-mediated apoptosis in glioma cells via ER stress, CHOP-mediated DR5 upregulation and c-FLIP downregulation. Taken together, these results suggest that combined treatment of glioma cells with TRAIL and polyether ionophore antibiotics may offer an effective therapeutic strategy.
    Carcinogenesis 04/2013; · 5.64 Impact Factor

Publication Stats

1k Citations
301.11 Total Impact Points

Institutions

  • 2004–2014
    • Korea Basic Science Institute KBSI
      Sŏul, Seoul, South Korea
  • 2013
    • Eulji University
      Sŏngnam, Gyeonggi Province, South Korea
    • CHA University
      Sŏul, Seoul, South Korea
    • Yonsei University
      Sŏul, Seoul, South Korea
    • Sungkyunkwan University
      • Samsung Medical Center
      Seoul, Seoul, South Korea
  • 2011–2013
    • Gyeongsang National University
      • College of Veterinary Medicine
      Shinshū, South Gyeongsang, South Korea
    • Korea Food and Drug Administration
      Seishō-gun, North Gyeongsang, South Korea
  • 2008–2013
    • Asan Medical Center
      • Department of Gastroenterology
      Sŏul, Seoul, South Korea
  • 2007–2013
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
    • Konyang University
      Ronsan, South Chungcheong, South Korea
  • 2004–2013
    • Ajou University
      • Institute for Medical Sciences
      Seoul, Seoul, South Korea
    • Yonsei University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2012
    • Jeju National University
      Tse-tsiu, Jeju, South Korea
  • 2001–2011
    • Chungnam National University
      • • School of Bioscience and Biotechnology
      • • Department of Chemistry
      Daiden, Daejeon, South Korea
  • 2009–2010
    • Kyungpook National University
      • College of Nursing
      Daikyū, Daegu, South Korea
  • 2004–2008
    • Pusan National University
      • Department of Polymer Science and Engineering
      Pusan, Busan, South Korea
  • 2005
    • Korean Institute of Geoscience and Mineral Resources
      Sŏul, Seoul, South Korea
  • 2003
    • Keimyung University
      Sŏul, Seoul, South Korea
    • Sungshin Women's University
      Sŏul, Seoul, South Korea