Young Sik Lee

Korea University, Sŏul, Seoul, South Korea

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Publications (50)228.52 Total impact

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    ABSTRACT: Lymphocyte activation gene-3 (LAG-3; CD223), a structural homolog of CD4, binds to MHC class II molecules. Recent research indicated that signaling mediated by LAG-3 inhibits T cell proliferation, and LAG-3 serves as a key surface molecule for the function of regulatory T cells. Previous reports demonstrated that the majority of LAG-3 is retained in the intracellular compartments and is rapidly translocated to the cell surface upon stimulation. However, the mechanism by which LAG-3 translocates to the cell surface was unclear. In this study, we examined the trafficking of human LAG-3 under unstimulated as well as stimulated conditions of T cells. Under the unstimulated condition, the majority of LAG-3 did not reach the cell surface, but rather degraded within the lysosomal compartments. After stimulation, the majority of LAG-3 translocated to the cell surface without degradation in the lysosomal compartments. Results indicated that the cytoplasmic domain without Glu-Pro repetitive sequence is critical for the translocation of LAG-3 from lysosomal compartments to the cell surface. Moreover, protein kinase C signaling leads to the translocation of LAG-3 to the cell surface. However, two potential serine phosphorylation sites from the LAG-3 cytoplasmic domain are not involved in the translocation of LAG-3. These results clearly indicate that LAG-3 trafficking from lysosomal compartments to the cell surface is dependent on the cytoplasmic domain through protein kinase C signaling in activated T cells.
    Journal of immunology (Baltimore, Md. : 1950). 08/2014;
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    ABSTRACT: Previous studies have reported comorbidity of attention deficit and hyperactivity disorder (ADHD) and allergic diseases. The current study investigated ADHD like behavioral symptoms and parenting stress in pediatric allergic rhinitis.
    Psychiatry investigation 07/2014; 11(3):266-71. · 1.06 Impact Factor
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    ABSTRACT: Attention deficit hyperactivity disorder (ADHD) symptoms are associated with the deficit in executive functions. Playing Go involves many aspect of cognitive function and we hypothesized that it would be effective for children with ADHD.
    Psychiatry investigation 04/2014; 11(2):143-51. · 1.06 Impact Factor
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    ABSTRACT: Recent brain imaging studies suggested that both the frontal and temporal cortices are important candidate areas for mediating the symptoms of internet addiction. We hypothesized that deficits of prefrontal and temporal cortical function in patients with on-line game addiction (PGA) would be reflected in decreased levels of N-acetyl aspartate (NAA) and cytosolic, choline containing compound (Cho). Seventy three young PGA and 38 age and sex matched healthy control subjects were recruited in the study. Structural MR and 1H MRS data were acquired using a 3.0 T MRI scanner. Voxels were sequentially placed in right frontal cortex and right medial temporal cortices. In the right frontal cortex, the levels of NAA in PGA were lower than those in healthy controls. In the medial temporal cortex, the levels of Cho in PGA participants were lower than those observed in healthy controls. The Young Internet Addiction Scale (YIAS) scores and perseverative responses in PGA were negatively correlated with the level of NAA in right frontal cortex. The Beck Depressive Inventory (BDI) scores in the PGA cohort were negatively correlated with Cho levels in the right temporal lobe. To the best of our knowledge, this is the first MRS study of individuals with on-line game addiction. Although, the subjects with on-line game addiction in the current study were free from psychiatric co-morbidity, patients with on-line game addiction appear to share characteristics with ADHD and MDD in terms of neurochemical changes in frontal and temporal cortices.
    Journal of Psychiatric Research. 01/2014;
  • Hae Young Ko, Young Sik Lee, Soonhag Kim
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    ABSTRACT: MicroRNAs (miRNAs) are an abundant class of small noncoding RNA molecules that inhibit the expression of cognate genes in multicellular organisms. These small RNAs have been demonstrated to play crucial roles in a variety of biological processes including cell differentiation, proliferation, and survival. Knowledge of specific expression patterns of miRNAs is critical for functional studies. Here, we describe a bioluminescence reporter gene-based method to measure miRNA activity in cultured cells and mice using a Gaussia luciferase reporter gene controlled by miRNA binding sites in its 3'untranslated region. This method can be used to noninvasively monitor the expression patterns of functionally active miRNAs involved in different biological processes or diseases in mice.
    Methods in molecular biology (Clifton, N.J.) 01/2014; 1098:85-95. · 1.29 Impact Factor
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    ABSTRACT: Endogenous small interfering RNAs (endo-siRNAs) are a newly emerged class of small regulatory RNAs. In Drosophila melanogaster, the production of endo-siRNAs depends on the RNase III enzyme Dicer-2 (Dcr-2). Loss of dcr-2 function reduces the resistance of adult flies to various stresses and shortens their life span. The mutants also exhibit alterations in carbohydrate and lipid metabolism. These findings suggest that the endo-siRNA pathway plays a protective role during exposure to stress and aging in D. melanogaster, possibly by regulating metabolic homeostasis. Here, we describe the methods that were used to discover the phenotypes associated with endo-siRNA deficiency by using dcr-2 null mutants.
    Methods in molecular biology (Clifton, N.J.) 01/2014; 1173:51-8. · 1.29 Impact Factor
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    ABSTRACT: The development of gene delivery systems into embryos is challenging due to technical difficulties, delivery efficiency and toxicity. Here, we developed an organic compound (VisuFect)-mediated gene delivery system for zygotes. The VisuFect, which is hydrophilic and Cy5.5-labeled, was conjugated with poly(A) oligo (VFA). The VFA into CHO cells showed clathrin-mediated internalization and no toxicity. The VFA successfully penetrated through the zona pellucida of fertilized eggs of various species including pigs, zebrafish, drosophilas and mice. The experiment with VisuFect-mediated delivery of the miR34c inhibitor showed similar results with direct microinjection of the miR34c inhibitor by suppressing the development of zygotes up to the blastocyst stage. Noticeable features of the VisuFect will provide great benefits for further studies on gene function in sperms and embryos.
    Scientific reports. 01/2014; 4:5417.
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    ABSTRACT: Suicide among adolescents is an emerging global public health problem as well as a socioeconomic problem. Stress-coping strategies have been shown to be associated with suicidal ideation. We examined coping behaviors related to suicidal ideation and gender differences in adolescents using the data from the 2010 Korea Youth Risk Behavior Survey (ages 12-19 years; N = 73,238). Logistic regression analysis was used to evaluate associations between suicidal ideation and specific coping behaviors while controlling for potentially confounding variables. In both male and female groups, the coping behavior "drinking alcoholic beverages" and "smoking cigarettes" were positively associated with suicidal ideation. "Watching TV," "playing online/mobile games," and "sleeping" were negatively associated with suicidal ideation in both groups. In males, "engaging in sports" was negatively related to suicidal ideation. In females, "venting by talking to others" and "eating" were negatively related to suicidal ideation. The results indicate that there are gender differences in the effects of coping behaviors on adolescent suicidal ideation, and that developing adaptive coping strategies may function to reduce suicidality. Future studies are needed to examine whether improving coping skills can reduce suicidal ideation in a gender-specific manner.
    Anxiety, stress, and coping 12/2013; · 1.55 Impact Factor
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    ABSTRACT: To examine the short-term efficacy and tolerability of aripiprazole for children and adolescents with Tourette's disorder. This 10-week multicenter, double-blind, randomized, placebo-controlled trial was conducted from August 2008 to April 2010. Children and adolescents (aged 6-18 years) with a DSM-IV diagnosis of Tourette's disorder and a Yale Global Tic Severity Scale total tic score of 22 or more were randomly assigned (1:1 ratio) to placebo or aripiprazole. The primary outcome measure was mean change from baseline in the total tic score on the Yale Global Tic Severity Scale (last observation carried forward). Assessments of safety and tolerability included spontaneously reported adverse events, extrapyramidal symptoms, serum prolactin level, metabolic variables, and other laboratory evaluations. Of 61 subjects, 89% completed the study. Patients who received aripiprazole demonstrated a significant reduction from baseline to end of study on the mean (SD) total tic score of the Yale Global Tic Severity Scale compared to those who received placebo (-15.0 [8.4] and -9.6 [8.8], respectively,P=.0196). Response rate on the Tourette's Syndrome Clinical Global Impression-Improvement was 66% and 45% in the aripiprazole and placebo groups, respectively. Mean decrease in the Tourette's Syndrome Clinical Global Impression-Severity of Illness score was significantly different between the groups (P=.0321). In general, aripiprazole was well tolerated and there were no early discontinuations due to adverse events. The incidence of treatment-emergent adverse events between the groups was not significantly different (P=.7550). While aripiprazole decreased serum prolactin concentration (P<.0001), it increased mean body weight, body mass index, and waist circumference significantly (P=.0055,P=.0142, and P=.0270, respectively). In comparison with placebo, aripiprazole was efficacious, generally tolerated and safe in the short-term treatment of children and adolescents with Tourette's disorder. ClinicalTrials.gov identifier:NCT00706589.
    The Journal of Clinical Psychiatry 08/2013; 74(8):e772-80. · 5.81 Impact Factor
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    ABSTRACT: AIM: The problems of youth social withdrawal (or hikikomori) became a hot-button social issue in Japan in the 1990s. Unfortunately, current nosology in the DSM-IV may not adequately capture the concept of socially withdrawn youth (SWY) or hikikomori. This study aimed to investigate core SWY issues, evaluate SWY's psychopathologies, and approach them therapeutically through a home visitation program. METHODS: Participants were 65 youth referred by community mental health centers and psychiatric clinics around Seoul and Kyongki-Do province. Among them, only 41 participants (31 male, 10 female, mean age 15 ± 3.6 years) fit our SWY criteria. In addition, 248 middle and high school students in Seoul were recruited as a baseline control group. Caseworkers interviewed the SWY participants and their parents in their homes, using our structured interview manual and a number of psychiatric scales. Caseworkers also approached the participants therapeutically. RESULTS: Participants' Depression Inventory, Trait Anxiety Inventory, Social Anxiety Scale, and Internet Addiction Scale scores were significantly higher than those of baseline controls. Participants' mean number of psychotherapeutic sessions was 2.8, and the mean number of parental interview sessions was 3.4. After the therapeutic sessions, Global Assessment Functioning scores and social activities had improved somewhat in 68.3% of participants. CONCLUSION: These findings suggest that SWY is a complex phenomenon, so an individual psychopathologic process is very important for treatment. The most difficult problem in SWY treatment was therapeutic access. Hence, the home visit approach with a structured manual may be a good gateway for solving this problem.
    Psychiatry and Clinical Neurosciences 05/2013; 67(4):193-202. · 2.04 Impact Factor
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    ABSTRACT: The purpose of the current study was to evaluate possible overlapping substance abuse and internet addiction in a large, uniformly sampled population, ranging in age from 13 to 18years. Participants (N=73,238) in the current study were drawn from the 6th Korea Youth Risk Behavior Web-based Survey (KYRBWS-V) for students from 400 middle schools and 400 high schools in 16 cities within South Korea. Of adolescent internet users, 85.2% were general users (GU), 11.9% were users with potential risk for internet addiction (PR), and 3.0% were users with high risk for internet addiction (HR). There was a difference in the number of students with alcohol drinking among the GU, PR, and HR groups (20.8% vs 23.1% vs 27.4%). There was a difference in the number of students who smoked among the GS, PR, and HR groups (11.7% vs 13.5% vs 20.4%). There was a difference in the number of students with drug use among the GU, PR, and HR groups (1.7% vs 2.0% vs 6.5%). After adjusting for sex, age, stress, depressed mood, and suicidal ideation, smoking may predict a high risk for internet addiction (OR=1.203, p=0.004). In addition, drug use may predict a high risk for internet addiction (OR=2.591, p<0.001). Because students with a high risk for internet addiction have vulnerability for addictive behaviors, co-morbid substance abuse should be evaluated and, if found, treated in adolescents with internet addiction.
    Addictive behaviors 01/2013; 38(4):2022-2025. · 2.25 Impact Factor
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    ABSTRACT: Objectives : The objective of this study is to find out the differences in psychopathology, temperament, and character factors between young adults with and without childhood attention-deficit hyperactivity disorder (ADHD) symptoms. Methods : The subjects consisted of 314 university students (male=72, female=242) in Gongju. They were divided into childhood ADHD group (N=54) and normal group (N=260) to the Wender-Utah Rating Scale. Participants were assessed using Korean Adult ADHD Scale, Beck Depression Inventory-II, Beck Anxiety Inventory, Kimberly Young's Internet Addiction Test, Barratt Impulsiveness Scale, Paranoia Scale, Korean-Schizotypal Ambivalence Scale, Lubben Social Network Scale, and Temperament and Character Inventory-Revised. Descriptive statistics, t-test, chi-square, spearman correlation, and stepwise multiple regression were applied to analyze the data. Results : Participants with childhood ADHD symptoms had high level of adult ADHD symptoms (p
    Journal of the Korean Academy of Child and Adolescent Psychiatry. 01/2013; 24(4).
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    ABSTRACT: RNA interference is a eukaryotic regulatory mechanism by which small non-coding RNAs typically mediate specific silencing of their cognate genes. In Drosophila, the RNase III enzyme Dicer-2 (Dcr-2) is essential for biogenesis of endogenous small interfering RNAs (endo-siRNAs), which have been implicated in regulation of endogenous protein-coding genes. Although much is known about microRNA-based regulatory networks, the biological functions of endo-siRNAs in animals remain poorly understood. We performed gene expression profiling on Drosophila dcr-2 null mutant pupae to investigate transcriptional effects caused by a severe defect in endo-siRNA production, and found 306 up-regulated and 357 down-regulated genes with at least a 2-fold change in expression compared with the wild type. Most of these up-regulated and down-regulated genes were associated with energy metabolism and development, respectively. Importantly, mRNA sequences of 39% of the up-regulated genes were perfectly complementary to the sequences of previously reported endo-siRNAs, suggesting they may be direct targets of endo-siRNAs. We confirmed up-regulation of five selected genes matching endo-siRNAs and concomitant down-regulation of the corresponding endo-siRNAs in dcr-2 mutant pupae. Most of the potential endo-siRNA target genes were associated with energy metabolism, including the citric acid cycle and oxidative phosphorylation in mitochondria, implying that these are major metabolic processes directly affected by endo-siRNAs in Drosophila. Consistent with this finding, dcr-2 null mutant pupae had lower ATP content compared with controls, indicating that mitochondrial energy production is impaired in these mutants. Our data support a potential role for the endo-siRNA pathway in energy homeostasis through regulation of mitochondrial metabolism. J. Cell. Biochem. © 2012 Wiley Periodicals, Inc.
    Journal of Cellular Biochemistry 09/2012; · 3.06 Impact Factor
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    ABSTRACT: The purpose of the current study was to evaluate the efficacy of cognitive behavioral therapy (CBT) in combination with bupropion for treatment of problematic on-line game play in adolescents with co-morbid major depressive disorder. Sixty-five depressed adolescents with excessive on-line game play were randomly assigned to a CBT group (CBT-Med group (N = 32)) or a clinical control group (Med group (N = 33)). Measures of severity of internet use, depressive symptoms, anxiety symptoms, life satisfaction and school adaptation were assessed at baseline, after the 8 week intervention, and at the end of a 4 week follow-up post-treatment period. Young Internet Addiction Scale scores in the CBT-Med group were reduced compared to those of the Med group, but there was no significant difference in the change of depression scores between two groups. The mean anxiety scores in the CBT-Med group did not change while those in the Med group were increased. The mean life satisfaction scores in the CBT-Med group were increased compared to those of the Med group. CBT in combination with bupropion may be effective for the treatment of depressed adolescents with on-line game addiction, particularly in reducing on-line game play and anxiety, as well as in improving life satisfaction.
    Computers in Human Behavior 09/2012; 28(5):1954–1959. · 2.27 Impact Factor
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    ABSTRACT: Because of its superior stretchability, graphene exhibits rich structural deformation behaviours and its strain engineering has proven useful in modifying its electronic and magnetic properties. Despite the strain-sensitivity of the Raman G and 2D modes, the optical characterization of the native strain in graphene on silica substrates has been hampered by excess charges interfering with both modes. Here we show that the effects of strain and charges can be optically separated from each other by correlation analysis of the two modes, enabling simple quantification of both. Graphene with in-plane strain randomly occurring between -0.2% and 0.4% undergoes modest compression (-0.3%) and significant hole doping on thermal treatments. This study suggests that substrate-mediated mechanical strain is a ubiquitous phenomenon in two-dimensional materials. The proposed analysis will be of great use in characterizing graphene-based materials and devices.
    Nature Communications 08/2012; 3:1024. · 10.74 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) are a group of evolutionarily conserved small noncoding RNAs with regulatory functions. Increasing evidence suggests that polymorphisms in miRNA genes are associated with phenotypic variation by affecting miRNA expression and/or function. Here, we identified two single nucleotide polymorphisms (SNPs) in the porcine miR-1 locus, both of which were linked and located downstream from the stem-loop miRNA precursor sequence within the primary miR-1 region. An association study on muscle fiber characteristics and meat quality traits was performed with a total of 451 pigs representing three pig breeds (Berkshire, n=153; Landrace, n=125; Yorkshire, n=173). The miR-1 SNPs were significantly associated with type I and type IIa muscle fibers in number and area compositions, respectively, but not with meat quality traits. Notably, these polymorphisms were also significantly associated with altered expression of the primary miR-1 transcript, ultimately leading to comparable changes in the levels of both precursor and mature miR-1. Furthermore, altered miR-1 levels were correlated with the variation in muscle fiber composition. Our data suggest that miR-1 may be a candidate gene associated with muscle fiber type composition.
    Gene 06/2012; 506(1):211-6. · 2.20 Impact Factor
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    ABSTRACT: We evaluated whether a brief 3-week family therapy intervention would change patterns of brain activation in response to affection and gaming cues in adolescents from dysfunctional families who met criteria for on-line game addiction. Fifteen adolescents with on-line game addiction and fifteen adolescents without problematic on-line game play and an intact family structure were recruited. Over 3 weeks, families were asked to carry out homework assignments focused on increasing family cohesion for more than 1 hour/day and 4 days/week. Before therapy, adolescents with on-line game addiction demonstrated decreased activity as measured by functional magnetic resonance imaging (fMRI) within the caudate, middle temporal gyrus, and occipital lobe in response to images depicting parental affection and increased activity of the middle frontal and inferior parietal in response scenes from on-line games, relative to healthy comparison subjects. Improvement in perceived family cohesion following 3 weeks of treatment was associated with an increase in the activity of the caudate nucleus in response to affection stimuli and was inversely correlated with changes in on-line game playing time. With evidence of brain activation changes in response to on-line game playing cues and images depicting parental love, the present findings suggest that family cohesion may be an important factor in the treatment of problematic on-line game playing.
    Psychiatry Research 06/2012; 202(2):126-31. · 2.68 Impact Factor
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    ABSTRACT: MicroRNAs are a class of small non-coding RNA molecules that repress gene expression primarily at the post-transcriptional level. Genetic variations in microRNA genes may contribute to phenotypic differences by altering the expression of microRNAs and their targets. Here, we identified 12 single nucleotide polymorphisms (SNPs) in the genomic region of the porcine MIR206 / MIR133B cluster, 10 and 2 of which were associated with MIR206 and MIR133B respectively. All 12 SNPs were located within primary microRNAs. Allele frequency determination in different pig breeds (Berkshire, n = 153; Landrace, n = 125; Yorkshire, n = 173) and association studies of muscle fiber characteristics, lean meat production and meat quality traits were performed on the MIR206 and MIR133B SNPs. The MIR206 SNPs were associated with the percentage of type IIa and IIb fibers for muscle fiber area composition, meat quality traits including drip loss and lightness, and backfat thickness, a parameter of lean meat production. In addition, we found significant association of the MIR133B SNPs with total muscle fiber number, loin eye area, and muscle pH. Furthermore, these SNPs significantly affected the levels of mature MIR206 and MIR133B , respectively, primarily by regulating the processing of primary microRNAs into precursor microRNAs. Interestingly, altered MIR206 levels correlated with phenotypic variability among genotypes of the MIR206 SNP. Our data suggest that polymorphisms in the porcine MIR206 / MIR133B cluster are a genetic factor affecting muscle and meat quality traits.
    Animal Genetics 05/2012; · 2.58 Impact Factor
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    ABSTRACT: Methionine sulfoxide reductase B3A (MsrB3A), which catalyzes the stereospecific reduction of methionine-R-sulfoxide to methionine, is localized to the endoplasmic reticulum (ER). Here, we report a critical role of the ER-targeted MsrB3 in protection against ER stress in Drosophila and in mammalian cells. Flies overexpressing human MsrB3A exhibited significantly increased resistance to ER stress induced by dithiothreitol. These flies also showed slightly enhanced resistance to tunicamycin-induced ER stress. In addition, overexpression of MsrB3A in mammalian cells increased resistance to dithiothreitol- and thapsigargin-induced ER stresses. However, MsrB3A overexpression had no effect on the resistance to tunicamycin-induced ER stress. Knockdown of MsrB3A in mammalian cells led to a significant decrease in the resistance to thapsigargin-induced ER stress, but had no effects on the resistance to either dithiothreitol- or tunicamycin-induced ER stress. Collectively, our data provide evidence that the ER-type of MsrB3 plays an important role in protection against ER stress, suggesting that MsrB3 may be involved in the regulation of ER homeostasis.
    Biochemical and Biophysical Research Communications 03/2012; 420(1):130-5. · 2.28 Impact Factor
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    ABSTRACT: Methionine sulfoxide reductase B (MsrB) is an enzyme that repairs oxidatively damaged proteins by specifically reducing methionine-R-sulfoxide back to methionine. Three MsrBs, localized in different cellular compartments, are expressed in mammals. However, the physiological roles of each MsrB with regard to its location remain poorly understood. Here, we expressed endoplasmic reticulum (ER)-targeted human MsrB3A (hMsrB3A) in Drosophila and examined its effects on various phenotypes. In two independent transgenic lines, both ubiquitous and neuronal expression of hMsrB3A rendered flies resistant to oxidative stress. Interestingly, these flies also showed significantly enhanced cold and heat tolerance. More strikingly, expression of hMsrB3A in the whole body and nervous system extended the lifespan of fruit flies at 29 °C by 43-50% and 12-37%, respectively, suggesting that the targeted expression of MsrB in the ER regulates Drosophila lifespan. A significant increase in lifespan was also observed at 25 °C only when hMsrB3A was expressed in neurons. Additionally, hMsrB3A overexpression significantly delayed the age-related decline in locomotor activity and fecundity. Taken together, our data provide evidence that the ER type of MsrB, MsrB3A, plays an important role in protection mechanisms against oxidative, cold and heat stresses and, moreover, in the regulation of fruit fly aging.
    Biochemical and Biophysical Research Communications 03/2012; 419(1):20-6. · 2.28 Impact Factor

Publication Stats

2k Citations
228.52 Total Impact Points

Institutions

  • 2008–2014
    • Korea University
      • • College of Life Sciences
      • • Department of Biotechnology
      Sŏul, Seoul, South Korea
    • National Fisheries Research and Development Institution
      Sŏul, Seoul, South Korea
  • 2005–2014
    • Chung-Ang University Hospital
      Sŏul, Seoul, South Korea
  • 2013
    • Korea Brain Research Institute
      Daikyū, Daegu, South Korea
  • 2012–2013
    • Chung-Ang University
      • College of Medicine
      Sŏul, Seoul, South Korea
  • 2003–2009
    • Northwestern University
      • Department of Cell and Molecular Biology
      Evanston, Illinois, United States
  • 2007–2008
    • Harvard Medical School
      • Department of Psychiatry
      Boston, MA, United States