Sung Won Park

Dankook University, Eidō, Chungcheongbuk-do, South Korea

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Publications (82)160.78 Total impact

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    ABSTRACT: Mucolipidoses II and III (ML II and ML III) are lysosomal disorders in which the mannose 6-phosphate recognition marker is absent from lysosomal hydrolases and other glycoproteins due to mutations in GNPTAB, which encodes two of three subunits of the heterohexameric enzyme, N-acetylglucosamine-1-phosphotransferase. Both disorders are caused by the same gene, but ML II represents the more severe phenotype. Bone manifestations of ML II include hip dysplasia, scoliosis, rickets and osteogenesis imperfecta. In this study, we sought to determine whether a recombinant adeno-associated viral vector (AAV2/8-GNPTAB) could confer high and prolonged gene expression of GNPTAB and thereby influence the pathology in the cartilage and bone tissue of a GNPTAB knock out (KO) mouse model. The results demonstrated significant increases in bone mineral density and content in AAV2/8-GNPTAB-treated as compared to non-treated KO mice. We also showed that IL-6 (interleukin-6) expression in articular cartilage was reduced in AAV2/8-GNPTAB treated ML II mice. Together, these data suggest that AAV-mediated expression of GNPTAB in ML II mice can attenuate bone loss via inhibition of IL-6 production. This study emphasizes the value of the MLII KO mouse to recapitulate the clinical manifestations of the disease and highlights its amenability to therapy.
    No preview · Article · Feb 2016 · Molecular Genetics and Metabolism
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    ABSTRACT: Background Mucopolysaccharidosis type II (MPS II, Hunter syndrome), is caused by a deficiency of iduronate-2-sulfatase (IDS). Despite the therapeutic effect of intravenous enzyme replacement therapy (ERT), the central nervous system (CNS) defects persist because the enzyme cannot cross the blood-brain barrier (BBB). There have been several trials of direct infusion to the cerebrospinal space showing promising results; however, this approach may have limitations in clinical situations such as CNS infection. The objective of this study was to improve the CNS defect with systemic high-dose ERT. Methods Systemic ERT was performed using three doses (1, 5, and 10 mg/kg weekly) of IDS for three different durations (1, 3, and 6 months) in IDS knock out (KO) mice of two age groups (2 months, 8 months). GAG measurement in tissues, brain pathology, and behavioral assessment were analyzed. Results Brain IDS activities increased in parallel with the concentrations of IDS injected. The glycosaminoglycan (GAG) level and histopathology in the brains of the young mice improved in a dose- and duration-dependent manner; however, those were not improved in the old mice, even at higher doses of IDS. The spontaneous alternation behavior was recovered in young KO mice treated with ≥ 5 mg/kg IDS; however, no significant improvement was observed in old KO mice. Conclusions These results suggest that high-dose ERT given to mice of earlier ages may play a role in preventing GAG accumulation and preventing CNS damage in IDS KO mice. Therefore, ERT above the present standard dose, starting in early childhood, could be a promising treatment regimen for reducing neurological impairment in Hunter syndrome. Electronic supplementary material The online version of this article (doi:10.1186/s13023-015-0356-0) contains supplementary material, which is available to authorized users.
    Full-text · Article · Dec 2015 · Orphanet Journal of Rare Diseases
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    ABSTRACT: The current recombinant human growth hormone (rhGH) therapy requires daily subcutaneous (sc) injections, which results in poor patient compliance, especially in young children. To reduce the dosing frequency, we generated a chimeric protein of rhGH and the Fc-domain of immunoglobulin G (IgG) (rhGH-Fc). The pharmacokinetics and pharmacodynamics of sc-injected rhGH-Fc were assessed in male Sprague-Dawley rats and hypophysectomized rats, respectively. A single sc injection of rhGH-Fc at a dose of 0.2 mg/kg slowly reached a Cmax of 16.80 ng/mL and remained for 7 days with a half-life of 51.1 h. Conversely, a single sc injection of rhGH 0.2 mg/kg rapidly reached a Cmax of 46.88 ng/mL and declined with a half-life of 0.55 h to baseline values in 4 h. In the efficacy study, the sc-injected rhGH-Fc induced rapid weight gain and tibial width growth at a dose of 240 μg/animal. The effect of two injections of rhGH-Fc separated by 1 week was comparable to that of the same dose of 14 daily injections of rhGH. The rhGH-Fc is a novel candidate for long-acting rhGH therapy with more convenient weekly administration, as it reduces glomerular filtration and receptor-mediated clearance while allowing for the rapid reversal of potential adverse events.
    Full-text · Article · Sep 2015 · Molecular Pharmaceutics
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    ABSTRACT: Patients with Marfan syndrome (MFS) presents with primary skeletal manifestations such as tall stature, chest wall abnormality, and scoliosis. These primary skeletal manifestations affect the growth pattern in MFS. Therefore, it is not appropriate to use normal growth charts to evaluate the growth status of MFS. We aimed to develop disease-specific growth charts for Korean MFS patients and to use these growth charts for understanding the growth patterns in MFS and managing of patients with MFS. Anthropometric data were available from 187 males and 152 females with MFS through a retrospective review of medical records. Disease-specific growth charts were generated and 3, 25, 50, 75, and 97 percentiles were calculated using the LMS (refers to λ, μ, and σ, respectively) smoothing procedure for height and weight. Comparisons between MFS patients and the general population were performed using a one-sample t-test. With regard to the height, the 50th percentile of MFS is above the normative 97th percentile in both genders. With regard to the weight, the 50 percentile of MFS is above the normative 75th percentile in male and between the normative 50th percentile and the 75th percentile in female. The disease-specific growth charts for Korean patients with MFS can be useful for monitoring growth patterns, planning the timing of growth-reductive therapy, predicting adult height and recording responses to growth-reductive therapy.
    Full-text · Article · Jul 2015 · Journal of Korean Medical Science

  • No preview · Article · May 2015 · Cancer Research
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    Su Jin Kim · Sung Won Park · Younghee Kwun · Dong-Kyu Jin

    Preview · Article · Apr 2015 · International Journal of Pediatric Endocrinology
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    ABSTRACT: To standardize the corneal haze model in the resection depth and size for efficient corneal haze development, the new method of air assisted lamellar keratectomy was performed. The ex vivo porcine corneas were categorized into 4 groups depend on the trephined depth: 250(G1), 375(G2), 500(G3) and 750-μm(G4). The stroma was equally ablated at the five measurement sites in all groups. Significant difference was observed between the trephined corneal depths for resection and ablated corneal thickness in G1 (P<0.001). No significant differences were detected between the trephined corneal depth for resection and the ablated corneal thickness in G2, G3, and G4. The resection percentage was similar in all groups after microscopic imaging of corneal sections. The air assisted lamellar keratectomy (AK) and conventional keratectomy (CK) method were performed on six beagles in vivo. Development of corneal haze was evaluated every week until 28 days postoperatively. The occurrence of corneal haze in AK-group was significantly greater than that in CK-group beginning 14 days after surgery. Alpha-smooth muscle actin expression was significantly higher in AK-group (P<0.001) than that in CK-group. The air assisted lamellar keratectomy was used to achieve a desired corneal thickness after resection and to produce sufficient corneal haze.
    Preview · Article · Mar 2015 · Journal of veterinary science (Suwŏn-si, Korea)

  • No preview · Conference Paper · Jan 2015
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    ABSTRACT: Schmid-type metaphyseal chondrodysplasia (MCDS) is characterized by short stature with short legs, bowing of the long bones, coxa vara, and waddling gait. MCDS is a relatively common form of MCD. Most mutations that cause MCDS occur within the carboxyl-terminal non-collagenous domain (NC1) of the COL10A1 gene. We performed mutational analysis of the COL10A1 genes in 4 unrelated Korean patients with diagnosed MCDS. Mutational analysis of COL10A1 identified c.1904_1915delinsT (p.Gln635LeufsX10) and c.1969dupG (p.Ala657GlyfsX10), 2 novel frameshift mutations, and c.2030T>A (p.Val677Glu) and c.862G>C (p.Gly288Arg) at unusual mutational sites, which could be pathogenic. We present the first report of the molecular characteristics of MCDS in 4 Korean patients. Our findings suggest that a novel sequence variation involving an unusual mutational site of the COL10A1 gene can cause mild MCDS. Copyright © 2014. Published by Elsevier Masson SAS.
    No preview · Article · Dec 2014 · European Journal of Medical Genetics
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    ABSTRACT: Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders that are characterized by susceptibility to bone fractures, and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Most patients have defects in type I collagen biosynthesis with autosomal dominant inheritance; but, many autosomal recessive genes have been reported. We applied whole exome sequencing to identify mutations in a Korean OI patient who had an umbilical hernia, frequent fractures, a markedly short stature, delayed motor development, scoliosis, and dislocation of the radial head, with a bowed radius and ulna. We identified two novel variants in the BMP1 gene: c.808A>G and c.1297G>T. The former variant caused a missense change p.(Met270Val) and the latter variant caused the skipping of exon 10. The hypo-functional nature of the two variants was demonstrated in a zebrafish assay.This article is protected by copyright. All rights reserved
    Full-text · Article · Nov 2014 · Human Mutation
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    ABSTRACT: Purpose The reliability of the quantitative measurement of breast density with a semi-automated thresholding method (Cumulus™) has mainly been investigated with film mammograms. This study aimed to evaluate the intrarater reproducibility of percent density (PD) by Cumulus™ with digital mammograms. Methods This study included 1,496 craniocaudal digital mammograms from the unaffected breast of breast cancer patients. One rater reviewed each mammogram and estimated the PD using the Cumulus™ method. All images were reassessed by the same rater 1 month later without reference to the previously assigned values. The repeatability of the PD was evaluated by an intraclass correlation coefficient (ICC). All patients were grouped based on their body mass index (BMI), age, family history of breast cancer, breastfeeding history and breast area (calculated with Cumulus™), and subgroup analysis for the ICC of each group was performed. All patients were categorized by their Breast Imaging Reporting and Data System (BI-RADS) density pattern, and the mean and standard deviation of the PD by each BI-RADS categories were compared. Results The ICC for the PD was 0.94, indicating excellent repeatability. The discrepancy between the paired PD values ranged from 0 to 23.93, with an average of 3.90 (standard deviation=3.39). The subgroup ICCs for the PD ranged from 0.88 to 0.96, indicating excellent reliability in all subgroups regardless of patient variables. The ICCs of the PD for the high-risk (BI-RADS 3 and 4) and low-risk (BI-RADS 1 and 2) groups were 0.90 and 0.88, respectively. Conclusion This study suggests that PD calculated with digital mammograms has an acceptable reliability regardless of patient age, BMI, family history of breast cancer, breastfeeding history, breast size, and BI-RADS density pattern.
    Full-text · Article · Jun 2014 · Journal of Breast Cancer
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    Sang-Hyun Kim · Hyun Seok · Seung Yeol Lee · Sung Won Park
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    ABSTRACT: An acetabular paralabral cyst is a benign soft tissue cyst usually seen in association with a tear of the acetabular labrum. Acetabular paralabral cysts are often the cause of joint pain, but they rarely cause compression of the adjacent neurovascular structures. We present a case of a 63-year-old male patient who had paresis and atrophy of right hip adductor muscles. Right obturator neuropathy was confirmed through an electrodiagnostic study. In addition, magnetic resonance imaging showed a paralabral cyst in the right acetabulum which extended to the pelvic wall. The patient underwent conservative treatment without surgical procedure. The pain was decreased after 1 month of conservative therapy. The pain was decreased at the 1-month follow-up. Follow-up electromyography showed polyphasic motor unit potentials in adductor magnus and adductor longus muscles. Based on the experience of this case, an acetabular paralabral cyst should be considered as one of the rare causes of obturator neuropathy.
    Preview · Article · Jun 2014 · Annals of Rehabilitation Medicine
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    ABSTRACT: Hunter syndrome (or mucopolysaccharidosis type II [MPS II]) arises because of a deficiency in the lysosomal enzyme iduronate-2-sulfatase. Short stature is a prominent and consistent feature in MPS II. Enzyme replacement therapy (ERT) with idursulfase (Elaprase®) or idursulfase beta (Hunterase®) have been developed for these patients. The effect of ERT on the growth of Korean patients with Hunter syndrome was evaluated at a single center. This study comprised 32 patients, who had received ERT for at least 2 yr; they were divided into three groups according to their ages at the start of ERT: group 1 (<6 yr, n=14), group 2 (6-10 yr, n=11), and group 3 (10-20 yr, n=7). The patients showed marked growth retardation as they got older. ERT may have less effect on the growth of patients with the severe form of Hunter syndrome. The height z-scores in groups 2 and 3 revealed a significant change (the estimated slopes before and after the treatment were -0.047 and -0.007, respectively: difference in the slope, 0.04; P<0.001). Growth in response to ERT could be an important treatment outcome or an endpoint for future studies. Graphical Abstract
    Full-text · Article · Feb 2014 · Journal of Korean medical science
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    ABSTRACT: Embryonic stem cell test is a valuable model for evaluating developmental toxicity because the in vitro developmental process mimics in vivo. This study aimed to assess the neurotoxic effects of chemicals by quantifying neural-specific proteins in vitro. Quantitation of the markers during 14-d-differentiation indicated that the mouse embryonic stem cells were completely differentiated into neural cells on day 8. Non-cytotoxic concentrations of methylmercury (MM), arsanilic acid (AA) and danofloxacin (DF) treated on the differentiating and the differentiated stage. Low exposure of MM decreased the expression of GABAA-R in the differentiating stage and of Nestin in the differentiated stage. However, GFAP, Tuj1 and MAP2 were affected only by relatively high dosages in both stages. AA affected the quantities of GABAA-R and GFAP in the differentiated stage, but the quantitative changes of Nestin and Tuj1 were greater in the differentiating stage. For those neural markers (except Nestin) expressed by both stages, DF affected at lower concentrations in the differentiated stage than the differentiating stage. Acetylcholinesterase activity was inhibited by relatively low dosages of MM and AA in the differentiating stage, while this activity was inhibited only by more than 40 µM of DF in the differentiated stage. In conclusion, non-cytotoxic concentrations of chemicals differentially induced changes in marker expression between the treated groups as functions of the exposure dosages and stages. Our results could provide useful information for the different toxicities of chemicals in the neural development.
    Full-text · Article · Oct 2013 · Journal of veterinary science (Suwŏn-si, Korea)
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    Sung Won Park · Se Jin Park · Jae Il Shin

    Preview · Article · Sep 2013 · The Journal of Rheumatology
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    ABSTRACT: Purpose The purpose of the study was to evaluate endocrine patterns of patients with congenital adrenal hyperplasia and each gene mutation and to analyze the correlation between each phenotype and genotype. Methods This was a retrospective study of the patients with congenital adrenal hyperplasia in the pediatric outpatient clinic at the Samsung Medical Center from November 1994 to December 2012. We analyzed the medical records of 27 patients (male, 19; female, 8) with congenital adrenal hyperplasia who had been diagnosed by genetic testing to have 21-hydroxylase deficiency. Results In genetic analysis of 54 alleles from 27 patients, 13 types of mutations were identified. The distribution of 21-hydroxylase deficiency gene mutations revealed that intron 2 splice site (c.293-13A/C>G) mutations and large deletions were the most common, at 31.5% and 22.2% respectively, followed by p.I173N, p.R356W, and p.I172N mutations at 11.1%, 9.3%, and 9.3%, respectively. Other mutations were observed at 1.9-3.7%. No novel mutations were detected. Conclusion The analysis of 54 alleles revealed 13 types of mutation. The salt wasting form showed a good correlation between genotype and phenotype, but the simple virilizing and nonclassic forms showed inconsistencies between genotype and phenotype. The distribution of CYP21A2 mutations was evaluated for 21-hydroxylase deficiency patients from a single center. This study provides limited data on mutation spectrum and genotype-phenotype correlation of 21-hydroxylase deficiency in Korea.
    Full-text · Article · Sep 2013
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    ABSTRACT: Mucopolysaccharidosis II (MPS II, Hunter syndrome) is a rare X-linked lysosomal storage disorder caused by the deficiency of iduronate-2-sulfatase (IDS). In affected patients, glycosaminoglycan (GAG) accumulates in the lysosomes of many organs and tissues contributing to the pathology associated with MPS II. The objective of this phase I/II clinical study was to evaluate the efficacy and safety of recombinant human iduronate-2-sulfatase (idursulfase beta, Hunterase®) in the treatment of MPS II. Thirty-one MPS II patients between 6 and 35 years of age were enrolled in a randomized, single-blinded, active comparator-controlled phase I/II trial for 24 weeks. Patients were randomized to active comparator infusions (N=11), 0.5 mg/kg idursulfase beta infusions (N=10), or 1.0 mg/kg idursulfase beta infusions (N=10). The primary efficacy variable was the level of urinary GAG excretion. The secondary variables were changes in the distance walked in 6 minutes (6-minute walk test, 6MWT), echocardiographic findings, pulmonary function tests, and joint mobility. Patients in all three groups exhibited reduction in urine GAG and this reduced GAG level was maintained for 24 weeks. Urine GAG was also significantly reduced in the 0.5 mg/kg and 1.0 mg/kg idursulfase beta groups when compared to the active comparator group (P = 0.043, 0.002, respectively). Changes in 6MWT were significantly greater in the 0.5 mg/kg and 1.0 mg/kg idursulfase groups than in the active comparator group (p= 0.003, 0.015, respectively). Both idursulfase beta infusions were generally safe and well tolerated, and elicited no serious adverse drug reactions. The most frequent adverse events were urticaria and skin rash, which were easily controlled with administration of antihistamines. This study indicates that idursulfase beta generates clinically significant reduction of urinary GAG, improvements in endurance as measured by 6MWT, and it has an acceptable safety profile for the treatment of MPS II. Trial registration ClinicalTrials.gov: NCT01301898
    Full-text · Article · Mar 2013 · Orphanet Journal of Rare Diseases
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    ABSTRACT: Mucopolysaccharidosis IVA (MPS IVA; OMIM #253000) is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), a lysosomal enzyme involved in the catabolism of keratan and chondroitin sulfate. In this study, we examined biochemical and genetic data from 6 Korean patients presenting with classic MPS IVA by measuring GALNS activity in peripheral blood leukocytes and skin fibroblasts. We initially identified Korean patients with MPS IVA by clinical, biochemical, and genetic analyses. We performed PCR-direct sequencing to identify molecular defects of the GALNS gene in patients and assessed the mutational statuses of family members as well as 50 healthy unrelated subjects. In silico analyses were performed to check for novel mutations. The mean age of the six female patients was 8.0 ± 5.2 years (range: 2-17 years), and were all found to have severe reductions of GALNS enzyme. A total of 12 mutant alleles were identified, corresponding to 7 different mutations. Five novel mutations were c.218A>G (p.Y73C), c.451C>A (p.P151T), c.725C>G (p.S242C), c.752G>A (p.R251Q), and c.1000C>T (p.Q334X). Two other mutations were c.1156C>T (p.R386C) and c.1243-1G>A. Two mutations, c.451C>A and c.1000C>T, accounted for 58% of all mutations in this sample. © 2013 Wiley Periodicals, Inc.
    No preview · Article · Mar 2013 · American Journal of Medical Genetics Part A
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    ABSTRACT: Objective: Metabolic syndrome is a risk factor for age-related hearing impairment (ARHI). There are metabolic differences between abdominal adipose tissue present in subcutaneous and visceral areas. In this study, we investigated the association between abdominal fat composition, measured by computerized tomography (CT), and hearing thresholds. Patients and methods: We recruited 662 adults aged 40-82 years with normal or symmetrical sensorineural hearing loss who underwent fat measurement by CT. Linear regression models were used to address the association between risk factors, including abdominal fat composition, and average hearing levels at low and high frequencies. Results: After adjusting for age, systemic disease and other variables, a positive association between visceral adipose tissue (VAT) area and average hearing threshold was observed in women. In men, there was no significant association between abdominal fat composition and hearing threshold. Conclusion: Our findings show an association between VAT and hearing impairment in women. A reduction in visceral adiposity may help to prevent hearing loss in women.
    No preview · Article · Feb 2013 · Clinical Endocrinology
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    ABSTRACT: A clone (NVRQS-DON) to DON was prepared in this experiment. Using the NVRQS-DON, Ag or Ab-coated enzyme linked immunosorbent assay (ELISA) was prepared by coating the DON-BSA and DON mAb. Quantitative calculations for DON from DON ELISA ranged from 50 to 4,000 ng/mL and from 25 to 500 ng/mL (r2 > 0.99), respectively. The IC50s of DON, HT-2, 15-acetyl-DON, and nivalenol were 23.44, 22,545, 5,518, and 5,976 ng/mL, respectively, based on the DON-Ab ELISA. The cross-reactivity of the mAb to HT-2, 15-acetyl-DON, and nivalenol was 0.1, 0.42, and 0.40%, respectively. The intra- and interassay precision coefficient variations (CV) were both < 10%. The mAb-coated ELISA was validated by spiking DON (0 to 1,000 μg/kg in feed). Recoveries ranged from 68.34 to 95.49%, with the CVs ranging from 4.10 to 13.38%. A buffer solution of 250, 500 and 1,000 ng/mL DON was separated using 300 mg of NVRQS-DON and 3 mg of magnetic nanoparticles (MNPs). NVRQS-DON was coupled to the MNP in an antibody concentration-dependent manner. The recoveries of DON by this mAb-MNP system were 75.2, 96.9, and 88.1%. In conclusion, we developed competitive ELISAs for the detection of DON in animal feed and a new extraction tool for DON using mAb-coupled MNPs.
    Full-text · Article · Feb 2013 · Journal of veterinary science (Suwŏn-si, Korea)

Publication Stats

777 Citations
160.78 Total Impact Points

Institutions

  • 2015
    • Dankook University
      Eidō, Chungcheongbuk-do, South Korea
  • 2001-2015
    • Seoul National University
      Sŏul, Seoul, South Korea
  • 2014
    • Soonchunhyang University
      Onyang, South Chungcheong, South Korea
  • 2013-2014
    • Catholic Kwandong University
      • College of Medicine
      Gangneung, Gangwon-do, South Korea
    • Cheil General Hospital
      Sŏul, Seoul, South Korea
    • Animal Plant And Fisheries Quarantine And Inspection Agency
      Anyō, Gyeonggi-do, South Korea
  • 2011-2014
    • University of Ulsan
      Ulsan, Ulsan, South Korea
    • Hannam University
      Daiden, Daejeon, South Korea
    • Chonnam National University
      • College of Veterinary Medicine
      Gwangju, Gwangju, South Korea
  • 2009-2014
    • Sungkyunkwan University
      • Department of Pediatrics
      Sŏul, Seoul, South Korea
    • University of Toronto
      Toronto, Ontario, Canada
  • 2008-2012
    • Samsung Medical Center
      • Department of Pediatrics
      Sŏul, Seoul, South Korea
  • 2006-2011
    • Carnegie Mellon University
      • Department of Electrical and Computer Engineering
      Pittsburgh, Pennsylvania, United States
    • Eulji University
      • Department of Internal Medicine
      Seoul, Seoul, South Korea
  • 2010
    • Inje University Paik Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
    • Ulsan College
      Urusan, Ulsan, South Korea
  • 2007
    • Pukyong National University
      Tsau-liang-hai, Busan, South Korea
    • Hyundai Heavy Industries
      Urusan, Ulsan, South Korea
  • 2003
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
  • 1994
    • Korea University
      • Department of Electrical Engineering
      Seoul, Seoul, South Korea