Seung Il Kim

Yonsei University Hospital, Sŏul, Seoul, South Korea

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Publications (115)360.2 Total impact

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    ABSTRACT: Outer membrane vesicles (OMVs) are produced by various pathogenic Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. In this study, we isolated OMVs from a representative soil bacterium, Pseudomonas putida KT2440, which has biodegradative activity towards various aromatic compounds. Proteomic analysis identified the outer membrane proteins OprC, OprD, OprE, OprF, OprH, OprG, and OprW as major components of OMV of P. putida KT2440. The production of OMVs was dependent to the nutrient availability in the culture media, and up- or down-regulation of specific outer membrane proteins were observed according to culture conditions. In particular, porins (e.g., benzoate-specific porin, BenF-like porin) and enzymes (e.g., catechol 1,2-dioxygenase, benzoate dioxygenase) for benzoate degradation were uniquely found in OMVs prepared from P. putida KT2440 cultured in media containing benzoate as the energy source. OMVs of P. putida KT2440 showed low pathological activity towards cultured cells originated from human lung cells, suggesting their potential as adjuvants or OMV vaccine carriers. Our results suggest that the protein composition of OMVs of P. putida KT2440 reflects the characteristics of the total proteome of P. putida KT2440.
    Journal of Proteome Research 09/2014; · 5.06 Impact Factor
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    ABSTRACT: & Aims: Endoplasmic reticulum (ER) stress is implicated in the development of type 2 diabetes mellitus. ER stress activates the unfolded protein response pathway, which contributes to apoptosis and insulin resistance. We investigated the roles of cytochrome P450 4A (CYP4A) in regulation of hepatic ER stress, insulin resistance, and the development of diabetes in mice.
    Gastroenterology 06/2014; · 12.82 Impact Factor
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    ABSTRACT: The secretion of extracellular membrane vesicles (EMVs) is a common phenomenon that occurs in archaea, bacteria, and mammalian cells. EMVs contain biologically active proteins, which have diverse roles in biological processes. The outer membrane vesicles (OMVs) of Gram-negative bacteria and membrane vesicles (MVs) of Gram-positive bacteria have been discovered in various species. The main issues related to bacterial EMVs are their virulence, biogenesis mechanisms, host cell interaction mechanisms, and their potential use as new vaccine candidates. Recently, proteomics has become an essential tool for the characterization of EMVs. Proteomics is useful for the identification, quantification, and protein-protein interaction analysis of EMV protein components. This review describes the current understanding of secretory EMVs based on proteomic methods and the characteristics of various bacterial secretory EMVs. Finally, evidence for their potential roles and future applications are discussed.
    Current Protein and Peptide Science 05/2014; · 2.33 Impact Factor
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    ABSTRACT: Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer.Trial registration: Identifier NCT01589367.
    BMC Cancer 03/2014; 14(1):170. · 3.33 Impact Factor
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    ABSTRACT: Novosphingobium pentaromativorans US6-1 is a halophilic marine bacterium able to degrade polycyclic aromatic hydrocarbons (PAHs). Genome sequence analysis revealed that the large plasmid pLA1 present in N. pentaromativorans US6-1 consists of 199 ORFs and possess putative biodegradation genes that may be involved in PAH degradation. 1-DE/LC-MS/MS analysis of N. pentaromativorans US6-1 cultured in the presence of different PAHs and monocyclic aromatic hydrocarbons (MAHs) identified approximately 1,000 and 1,400 proteins, respectively. Up-regulated biodegradation enzymes, including those belonging to pLA1, were quantitatively compared. Among the PAHs, phenanthrene induced the strongest up-regulation of extradiol cleavage pathway enzymes such as ring-hydroxylating dioxygenase, putative biphenyl-2,3-diol 1,2-dioxygenase, and catechol 2,3-dioxygenase in pLA1. These enzymes lead the initial step of the lower catabolic pathway of aromatic hydrocarbons through the extradiol cleavage pathway and participate in the attack of PAH ring cleavage, respectively. However, N. pentaromativorans US6-1 cultured with p-hydroxybenzoate induced activation of another extradiol cleavage pathway, the protocatechuate 4,5-dioxygenase pathway, that originated from chromosomal genes. These results suggest that N. pentaromativorans US6-1 utilizes two different extradiol pathways and plasmid pLA1 might play a key role in the biodegradation of PAH in N. pentaromativorans US6-1.
    PLoS ONE 03/2014; 9(3):e90812. · 3.53 Impact Factor
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    ABSTRACT: To determine the genomic sequence of extensively drug-resistant Acinetobacter baumannii DU202 and to perform proteomic characterization of antibiotic resistance in this strain using genome data. The genome sequence of A. baumannii DU202 was determined using the Hi-Seq 2000 system and comparative analysis was performed to determine the unique characteristics of A. baumannii DU202. Previous proteomic results from the cell wall membrane fraction by one-dimensional electrophoresis and liquid chromatography combined with mass spectrometry analysis (1DE-LC-MS/MS), using the A. baumannii ATCC 17978 genome as a reference, were reanalysed to elucidate the resistance mechanisms of A. baumannii DU202 using strain-specific genome data. Additional proteomic data from the cytosolic fraction were also analysed. The genome of A. baumannii DU202 consists of 3660 genes and is most closely related to the Korean A. baumannii 1656-2 strain. More than 144 resistance genes were annotated in the A. baumannii DU202 genome, of which 72 that encoded proteins associated with antibiotic resistance were identified in the proteomic analysis of A. baumannii DU202 cultured in tetracycline, imipenem and Luria-Bertani broth (control) medium. Strong induction of β-lactamases, a multidrug resistance efflux pump and resistance-nodulation-cell division (RND) multidrug efflux proteins was found to be important in the antibiotic resistance responses of A. baumannii DU202. Combining genomic and proteomic methods provided comprehensive information about the unique antibiotic resistance responses of A. baumannii DU202.
    Journal of Antimicrobial Chemotherapy 01/2014; · 5.34 Impact Factor
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    ABSTRACT: Pseudomonas taeanensis MS-3(T), isolated from a crude oil-contaminated seashore in South Korea, is capable of degrading petroleum oils, such as gasoline, diesel, and kerosene. Here, we report the draft genome sequence of this strain, which consists of 5,477,045 bp, with a G+C content of 60.72%.
    Genome announcements. 01/2014; 2(1).
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    ABSTRACT: We presented the photoacoustic imaging (PAI) tool and to evaluate whether microcalcifications in breast tissue can be detected on photoacoustic (PA) images.
    PLoS ONE 01/2014; 9(8):e105878. · 3.53 Impact Factor
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    ABSTRACT: This study evaluated the efficacy and safety of S-1 combined with docetaxel (SD) following doxorubicin plus cyclophosphamide (AC) as neoadjuvant therapy in patients with HER2-negative, stage II-III breast cancer. Patients received AC every 3 weeks for four cycles followed by S-1 (30 mg/m2 orally b.i.d. on days 1-14) and docetaxel (75 mg/m2 i.v. on day 1) every 3 weeks for four cycles. The primary endpoint was the pathological complete response (pCR) rate in breast and axillary lymph nodes. The study included 49 patients with a median age of 43 years. The median breast tumor size was 4.0 cm by palpation. All patients were positive for involvement of axillary lymph node and five patients also had supraclavicular lymph node metastasis, which was confirmed by histological examination. In total, 85.4% of patients (41/49) completed eight cycles of therapy and 95.9% of patients (47/49) received curative surgery. The pCR rate was 22.5% (n = 11). The clinical response rate was 67.4%. During SD chemotherapy, the most frequent grade 3-4 toxicity was neutropenia (8.5% by cycle). There was a single treatment-related mortality from severe neutropenia. Grade 3 S-1 specific toxicities such as epigastric pain (12.2% by person), stomatitis (4.1% by person), and diarrhea (2.0% by person) were also observed. In particular, gastrointestinal discomfort led to dose reduction of S-1 in 45.8% of patients. Given all axillary lymph node positive diseases, neoadjuvant S-1 combined with docetaxel following AC showed a favorable anti-tumor activity but gastrointestinal discomfort should be carefully considered for future studies.Trial registration: NCT00994968.
    BMC Cancer 12/2013; 13(1):583. · 3.33 Impact Factor
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    ABSTRACT: Mouse double minute 2 (Mdm2) is a negative regulator of the tumor suppressor p53. The p53-Mdm2 pathway may play a role in cancer development and prognosis, although the role of p53-Mdm2 in breast cancer remains unclear. p53 and Mdm2 expressions were determined by immunohistochemistry of tissue microarrays of 865 breast cancer patients who underwent surgery. Clinicopathological characteristics and survival data were analyzed. Mdm2 expression was categorized into four groups: negative, cytoplasm positive, nucleus positive, and concurrent nuclear and cytoplasm positive (N+&C+). Negative, cytoplasm-positive, nucleus-positive, and N+&C+ expressions of Mdm2 were observed in 59.2, 10.9, 27.8, and 2.1 % of patients, respectively. The N+&C+ group was associated with larger tumor size, higher grade, negativity for estrogen and progesterone receptors, HER2 positivity, high Ki-67 index, p53 positivity, and triple negative breast cancer. p53-positive tumors showed poorer overall survival than p53-negative tumors. The nucleus-positive and N+&C+ groups showed poorer disease-free survival than the negative and cytoplasm-positive groups. In multivariate analysis, nuclear Mdm2 expression including the N+&C+ group was significantly related to poor prognosis. Concurrent nuclear and cytoplasmic Mdm2 expression was an independent prognostic factor in patients with breast cancer. Subcellular localization of Mdm2 expression should be considered in the evaluation of Mdm2 in breast cancer.
    International Journal of Clinical Oncology 11/2013; · 1.41 Impact Factor
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    ABSTRACT: Both total plasma and tumor-derived microvesicle (TMV)-associated miRNAs have been proposed as potential blood-based biomarkers for cancer diagnosis. However, there has been no comparison of the two types of miRNAs for biomarker discovery because of technological challenges of isolating TMVs from human plasma. The effective isolation of TMVs can be hardly achieved with conventional immunobead-based methods due to the high content of plasma proteins. In the current study, zwitterionic sulfobetaine-conjugated immunobeads are prepared using cluster of differentiation 83 (CD83) as a candidate protein marker for breast cancer-derived microvesicles. The zwitterionic immunobeads are more than 10-fold efficient for isolating TMVs from clinical plasma samples by suppressing nonspecific protein binding than conventional immunobeads. Early-stage breast cancer can be distinguished from benign breast disease by using the sulfobetaine-modified immunobeads, whereas conventional immunobeads show poor discriminatory performance. Further, we demonstrate that miRNAs in the form of TMVs offer a major improvement over total plasma miRNAs for early cancer detection. The analyses of miRNA expression levels show that in total, 6 miRNAs are significantly upregulated in the CD83-positive microvesicles of breast cancer patients, whereas differential miRNA expression is not detected on using total plasma RNA. The results indicate that our zwitterionic immunobead platform may constitute a powerful tool to identify circulating biomarkers and open a new avenue for highly sensitive blood-based cancer diagnostics.
    Biomaterials 10/2013; · 8.31 Impact Factor
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    ABSTRACT: The identification of novel diagnostic markers of pathogenic bacteria is essential for improving the accuracy of diagnoses and for developing targeted vaccines. Streptococcus pneumoniae is a significant human pathogenic bacterium that causes pneumonia. N-acetylglucosamine-6-phosphate deacetylase (NagA) was identified in a protein mixture secreted by S. pneumoniae and its strong immunogenicity was confirmed in an immuno-proteomic assay against the anti-serum of the secreted protein mixture. In this study, recombinant S. pneumoniae NagA protein was expressed and purified to analyze its protein characteristics, immunospecificity, and immunogenicity, thereby facilitating its evaluation as a novel diagnostic marker for S. pneumoniae. Mass spectrometry analysis showed that S. pneumoniae NagA contains four internal disulfide bonds and that it does not undergo post-translational modification. S. pneumoniae NagA antibodies successfully detected NagA from different S. pneumoniae strains, whereas NagA from other pathogenic bacteria species was not detected. In addition, mice infected with S. pneumoniae generated NagA antibodies in an effective manner. These results suggest that NagA has potential as a novel diagnostic marker for S. pneumoniae because of its high immunogenicity and immunospecificity.
    The Journal of Microbiology 10/2013; 51(5):659-64. · 1.28 Impact Factor
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    ABSTRACT: Breast-conserving surgery (BCS) in patients with large tumors shrunk by neoadjuvant chemotherapy (NCT) remains controversial. We investigated oncologic outcomes of BCS in patients receiving NCT to treat locally advanced breast cancer (LABC). We reviewed 1,994 patients who underwent surgery with/without NCT. Patients were categorized into three groups according to treatment methods: initial BCS, BCS after NCT (NCT-BCS), and mastectomy after NCT (NCT-MX). Their characteristics and outcomes were analyzed. The NCT-BCS group had earlier stage cancer, more hormone receptor-negative and triple-negative breast cancers (TNBC) than the NCT-MX group. However, outcomes did not differ statistically between the two groups. BCS patients receiving NCT were younger, and had more advanced, hormone receptor-negative, HER2-positive, and TNBC breast cancers than BCS patients without NCT. Patients with pathological complete remission (pCR) in the NCT-BCS group had better survival outcomes than non-pCR patients and the initial BCS group. By multivariate analysis in patients receiving NCT, final stage and TNBC were associated with poor overall survival (stage III: P = 0.008; TNBC: P = 0.01), however surgery type was not (P = 0.20). BCS after NCT is a safe option for LABC that responded well to NCT. Shrinking tumors with NCT allows more opportunities to apply BCS without compromising outcomes. J. Surg. Oncol. © 2013 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 09/2013; · 2.64 Impact Factor
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    ABSTRACT: To investigate the prognostic value of tumor markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels at diagnosis of systemic recurrence. After primary treatments of locoregional breast cancers, serum CA 15-3 and/or CEA concentrations were regularly measured, and systemic recurrences were identified in 351 patients between January 1999 and December 2009. The association between tumor marker levels at systemic recurrence and survival were investigated by univariate and multivariate analyses. Elevated CA 15-3 and CEA levels were identified in 194 of 349 (55.6 %) and 111 of 308 (36.0 %) patients, respectively, at diagnosis of systemic recurrence. Elevated levels of CA 15-3 and CEA were correlated with visceral or multiple recurrences and elevated preoperative levels. Elevation of CA 15-3 was more prominent in younger patients and in primary node-positive tumors, while CEA was elevated in older patients at diagnosis and in estrogen receptor (ER)-positive tumors. Elevated tumor markers as well as ER negativity, short disease-free interval, and advanced stage at initial diagnosis showed independent prognostic significance on multivariate analysis. Among 306 patients for whom levels of both tumor markers at recurrence were available, 106 patients without elevation of either marker showed significantly better overall survival than those with elevated levels of either one or both markers, and the significance persisted in multivariate analysis. Elevated serum CA 15-3 and CEA levels at recurrence suggest increased tumor burden and may be prognostic for survival for metastatic breast cancer patients.
    Breast Cancer Research and Treatment 09/2013; · 4.47 Impact Factor
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    Seung Il Kim, Soo Hyun Kim
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    ABSTRACT: Lotus-leaf-like structured PLCL copolymer films' surfaces were casted by using the solvent-nonsolvent casting method. PLCL copolymers were synthesized by well-known copolymerization process, and were confirmed by 1H-NMR analysis. The molecular weight was measured by gel permeation chromatography (GPC). The films were casted with various nonsolvent ratios. Tetrahydrofuran (THF) was used as the solvent and alcohols were used as the nonsolvent. Surface hydrophobic characteristic was confirmed by the water contact angle. The water contact angle was increased by surface topology modification. Prepared film surfaces were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM) and X-ray diffraction (XRD). Platelet adhesion tests on the modified film surfaces were evaluated by platelet-rich plasma (PRP). The cell adhesive behavior on the modified film surfaces was also evaluated. Prepared lotus-leaf-like structured film surfaces exhibited reduced platelet adhesion behavior.
    Fall meeting of Korean Society for Biomaterials; 09/2013
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    ABSTRACT: NELL2 was first identified as a mammalian homolog of the chicken NEL protein. It was expressed in neurons and has been suggested to play a role in cell survival. However, no clear evidence has yet been available for functions of NELL2. In this study, we found two E2F1 binding sites located in the NELL2 promoter region. We examined the expression of NELL2 and E2F1 in human breast cancer cells (MDA-MB231, MCF7) and bladder cancer cells (5637, UC5). In MDA-MB231 and 5637, the expression levels of NELL2 and E2F1 were higher. To examine the interaction between E2F1 and NELL2, the binding activity was checked by a promoter assay and chromatin immunoprecipitation. From the results, we suggest that NELL2 is a novel target gene of E2F1, which is a key regulator of cell proliferation. We reveal that expression of NELL2 is regulated by E2F1, specifically, mRNA and protein levels of NELL2 are elevated upon activation of exogenous E2F1. Moreover, cells overexpressing NELL2 increased their invasive ability and an enhancement of the effect was observed when NELL2 and E2F1 were coexpressed in MDA-MB231 cells. Therefore, we suggest a novel activity for NELL2 in cancer progression through the regulation of E2F1.
    DNA and cell biology 07/2013; · 2.28 Impact Factor
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    ABSTRACT: Analysis of cancer cells: A new technique isolates rare circulating tumor cells (CTCs) and analyzes their protein expression by the use of detachable beads and high-pore-density filters. This technique shows significantly improved efficiency in the isolation of rare CTCs from peripheral blood and enables accurate measurement of in situ protein-expression levels.
    Angewandte Chemie International Edition 07/2013; · 11.34 Impact Factor
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    ABSTRACT: BACKGROUND: The performance of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NCT) was investigated in patients with locally advanced breast cancer (LABC). METHODS: After NCT of 178 patients with cytology-proven axillary/supraclavicular nodes metastasis at the time of diagnosis, SLNB using radioisotope was performed including completion node dissection between 2008 and 2011. The detection rate, sensitivity, false negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were analyzed. RESULTS: SLNB was successfully performed in 169 (94.9 %) patients. Tumor nonresponse and extensive residual nodal disease were found to be significantly associated with detection failure of sentinel nodes. Sensitivity, FNR, NPV, and accuracy of SLNB were 78.0, 22.0, 75.8, and 87.0 %, respectively, and a greater number of retrieved SLNs increased all four of these performance measures. Conversion to node-negative disease was achieved in 69 (40.8 %) patients: 24 % of patients with the luminal A subtype, 51.6 % of patients with the luminal B, 51.7 % of patients with the HER2-enriched, and 58.5 % of patients with the triple-negative breast cancer (TNBC) subtype. Luminal B, HER2-enriched, and TNBC subtypes showed comparable responses to NCT; however, the TNBC subtype had a significantly better FNR and accuracy. CONCLUSIONS: SLNB was found to be technically feasible, but its routine use was not recommended for LABCs after NCT. However, acceptable performance was noted for locally advanced TNBCs, and thus SLNB might be safely considered in these selected patients.
    Annals of Surgical Oncology 05/2013; · 4.12 Impact Factor
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    ABSTRACT: It is unnecessary to perform axillary staging in patients with ductal carcinoma in situ (DCIS) of the breast because of the low incidence of axillary metastasis. However, diagnosis of DCIS by core needle biopsy showed a high rate of underestimation of invasive cancer. Thus, it is necessary to predict invasiveness in DCIS patients on core before surgery. We analyzed 340 patients with DCIS diagnosed by needle biopsy. The cases were divided into training and validation sets. Logistic regression was performed to predict the presence of invasive cancer in the final pathology, and a nomogram was constructed from the training set using the presence of palpability, the presence of ultrasonographic calcification and mass, the biopsy tools, and the presence of microinvasion. The model was subsequently applied to the validation set. The nomogram for the training set was both accurate and discriminating, with an area under the receiver operating characteristic curve (AUC) of 0.75. When applied to the validation group, the model accurately predicted the likelihood of invasive cancer (AUC: 0.71). Our nomogram will allow surgeons to easily and accurately estimate the likelihood of invasive cancer in patients with DCIS as diagnosed by preoperative needle biopsy.
    Breast (Edinburgh, Scotland) 04/2013; · 2.09 Impact Factor
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    ABSTRACT: Abstract Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, and notorious for resistance to chemoradiotherapy. MicroRNAs (miRNAs) are significantly involved in the initiation and progression of numerous cancers; however, the role of miRNAs in recurrence of tumors remains unknown. Here we tried to identify novel miRNAs that are differentially expressed in recurrent GBM. Tissue samples were obtained from patients with primary and recurrent GBM treated with chemoradiotherapy, and the expression changes of miRNAs were measured by microarray. A total of 318 miRNAs were expressed in the GBM patients. The expression of 43 miRNAs were significantly altered at least 2-fold in primary and recurrent GBMs. Bioinformatic analysis revealed that the differentially expressed miRNAs and their putative target genes were mainly involved in cell death, cellular development, and cellular growth and proliferation, which are the key regulators for stem cells. Pathway analysis supported that the miRNAs may regulate signaling associated with induction and maintenance of cancer and stem cell, such as p53, ErbB1, Notch, Wnt, and TGF-β signaling pathways. These data suggest that, in recurrent GBM, growth factor and anti-apoptotic signalings for cancer cell growth and proliferation are regulated by miRNAs. Our findings will aid future research in understanding the pathophysiology of recurrent GBM and identifying diagnostic markers and/or therapeutic targets for recurrence of GBM.
    Omics: a journal of integrative biology 04/2013; · 2.29 Impact Factor

Publication Stats

911 Citations
360.20 Total Impact Points


  • 2011–2014
    • Yonsei University Hospital
      • Surgery
      Sŏul, Seoul, South Korea
    • Kyungpook National University Hospital
      Sŏul, Seoul, South Korea
  • 1998–2014
    • Korea Basic Science Institute KBSI
      • Division of Magnetic Resonance Research
      Sŏul, Seoul, South Korea
  • 2013
    • Yonsei University
      • Department of Surgery
      Sŏul, Seoul, South Korea
    • Korea Institute of Science and Technology
      • Center for Biomaterials
      Sŏul, Seoul, South Korea
  • 1999–2013
    • Dong-A University
      • • College of Natural Sciences
      • • Department of Biology and Biomedical Science
      Pusan, Busan, South Korea
  • 2012
    • Soongsil University
      • Department of Statistics and Actuarial Science
      Seoul, Seoul, South Korea
  • 2009
    • Korea Research Institute of Bioscience and Biotechnology KRIBB
      • Korean BioInformation Center
      Ansan, Gyeonggi, South Korea
  • 2008
    • Seoul National University
      • Department of Biological Sciences
      Sŏul, Seoul, South Korea
  • 2002
    • Jeju National University
      Tse-tsiu, Jeju, South Korea