Nayoung Kim

Fast Synthesis of High-Performance Graphene Films by Hydrogen-Free Rapid Thermal Chemical Vapor Deposition

The practical use of graphene in consumer electronics has not been demonstrated since the size, uniformity, and reliability problems are yet to be solved to satisfy industrial standards. Here we report mass-produced graphene films synthesized by hydrogen-free rapid thermal chemical vapor deposition (RT-CVD), roll-to-roll etching, and transfer methods, which enabled faster and larger production of homogeneous graphene films over 400 × 300 mm(2) area with a sheet resistance of 249 ± 17 Ω/sq without additional doping. The properties of RT-CVD graphene have been carefully characterized by high-resolution transmission electron microscopy, Raman spectroscopy, chemical grain boundary analysis, and various electrical device measurements, showing excellent uniformity and stability. In particular, we found no significant correlation between graphene domain sizes and electrical conductivity, unlike previous theoretical expectations for nanoscale graphene domains. Finally, the actual application of the RT-CVD films to capacitive multitouch devices installed in the most sophisticated mobile phone was demonstrated.

Atypical hemolytic uremic syndrome: Korean pediatric series.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in the Asian population. We studied a Korean pediatric cohort to delineate the clinical characteristics and genotypes.

Good Laboratory Standards for Clinical Next-Generation Sequencing Cancer Panel Tests

Next-generation sequencing (NGS) has recently emerged as an essential component of personalized cancer medicine due to its high throughput and low per-base cost. However, no sufficient guidelines for implementing NGS as a clinical molecular pathology test are established in Korea. To ensure clinical grade quality without inhibiting adoption of NGS, a taskforce team assembled by the Korean Society of Pathologists developed laboratory guidelines for NGS cancer panel testing procedures and requirements for clinical implementation of NGS. This consensus standard proposal consists of two parts: laboratory guidelines and requirements for clinical NGS laboratories. The laboratory guidelines part addressed several important issues across multistep NGS cancer panel tests including choice of gene panel and platform, sample handling, nucleic acid management, sample identity tracking, library preparation, sequencing, analysis and reporting. Requirements for clinical NGS tests were summarized in terms of documentation, validation, quality management, and other required written policies. Together with appropriate pathologist training and international laboratory standards, these laboratory standards would help molecular pathology laboratories to successfully implement NGS cancer panel tests in clinic. In this way, the oncology community would be able to help patients to benefit more from personalized cancer medicine.

Comprehensive genetic exploration of skeletal dysplasia using targeted exome sequencing

Purpose:The purpose of this study was to evaluate the clinical utility of targeted exome sequencing (TES) as a molecular diagnostic tool for patients with skeletal dysplasia.Methods:A total of 185 patients either diagnosed with or suspected to have skeletal dysplasia were recruited over a period of 3 years. TES was performed for 255 genes associated with the pathogenesis of skeletal dysplasia, and candidate variants were selected using a bioinformatics analysis. All candidate variants were confirmed by Sanger sequencing, correlation with the phenotype, and a cosegregation study in the family.Results:TES detected “confirmed” or “highly likely” pathogenic sequence variants in 74% (71 of 96) of cases in the assured clinical diagnosis category and 20.3% (13 of 64 cases) of cases in the uncertain clinical diagnosis category. TES successfully detected pathogenic variants in all 25 cases of previously known genotypes. The data also suggested a copy-number variation that led to a molecular diagnosis.Conclusion:This study demonstrates the feasibility of TES for the molecular diagnosis of skeletal dysplasia. However, further confirmation is needed for a final molecular diagnosis, including Sanger sequencing of candidate variants with suspected, poorly captured exons.Genet Med 18 6, 563–569.

Hydrazine Doped Graphene and Its Stability

The electronic property of graphene was investigated by hydrazine treatment. Hydrazine (N₂H₄) highly increases electron concentrations and up-shifts Fermi level of graphene based on significant shift of Dirac point to the negative gate voltage. We have observed contact resistance and channel length dependent mobility of graphene in the back-gated device after hydrazine monohydrate treatment and continuously monitored electrical characteristics under Nitrogen or air exposure. The contact resistance increases with hydrazine-treated and subsequent Nitrogen-exposed devices and reduces down in successive Air-exposed device to the similar level of pristine one. The channel conductance curve as a function of gate voltage in hole conduction regime keeps analogous value and shape even after Nitrogen/Air exposure specially whereas, in electron conduction regime change rate of conductance along with the level of conductance with gate voltage are decreased. Hydrazine could be utilized as the highly effective donor without degradation of mobility but the stability issue to be solved for future application.

Wide Field Imaging Analysis of Graphene

A Raman spectrometer is essential for analyzing the characteristics of graphene. The commercial micro-Raman spectrometer is useful for measuring small areas, but due to the small measuring area, it has limited use in industry, as a sampling measure. This paper suggests a Raman spectrometer able to get a large area image of graphene. By using this image, we can get information on defects and on the presence of graphene. Therefore, this equipment can be used for quality assessment for production of graphene.

Involvement of DDX6 gene in radio- and chemoresistance in glioblastoma

CCRT (concomitant chemotherapy and radiation therapy) is often used for glioblastoma multiforme (GBM) treatment after surgical therapy, however, patients treated with CCRT undergo poor prognosis due to development of treatment resistant recurrence. Many studies have been performed to overcome these problems and to discover genes influencing treatment resistance. To discover potential genes inducing CCRT resistance in GBM, we used whole genome screening by infecting shRNA pool in patient-derived cell. The cells infected ~8,000 shRNAs were implanted in mouse brain and treated RT/TMZ as in CCRT treated patients. We found DDX6 as the candidate gene for treatment resistance after screening and establishing DDX6 knock down cells for functional validation. Using these cells, we confirmed tumor associated ability of DDX6 in vitro and in vivo. Although proliferation improvement was not found, decreased DDX6 influenced upregulated clonogenic ability and resistant response against radiation treatment in vivo and in vitro. Taken together, we suggest that DDX6 discovered by using whole genome screening was responsible for radio- and chemoresistance in GBM.

Abstract 2931: Integrated genomic approaches identify upregulation of SCRN1 as a novel mechanism associated with acquired resistance to erlotinib in non small cell lung cancer cells with oncogenic EGFR mutation

Therapies targeting the tyrosine kinase activity of Epidermal Growth Factor Receptor (EGFR) have been proven to be effective in treating a subset of non-small cell lung cancer (NSCLC) patients harboring activating EGFR mutations. Inevitably these patients develop resistance to the EGFR-targeted tyrosine kinase inhibitors (TKIs). Here, we performed integrated genomic analyses using an in vitro system to uncover alternative genomic alterations responsible for acquired resistance to EGFR-TKIs. Specifically, we identified 80 genes whose expression is significantly increased in the resistant clones and RNAi-based systematic synthetic lethal screening revealed that suppression of one upregulated transcript, SCRN1, a secernin family member, restores sensitivity to erlotinib by enhancing inhibition of PI3K/AKT signaling pathway. Furthermore, we detected increased levels of SCRN1 in 5 of 11 lung tumor specimens from EGFR-TKIs refractory patients by immunohistochemistry. Taken together, we propose that upregulation of SCRN1 is an additional mechanism associated with acquired resistance to EGFR-TKIs in a subset of lung cancer patients and that its suppression serves as a novel therapeutic strategy to overcome drug resistance in these patients. Citation Format: Nayoung Kim, Ahye Cho, Hideo Watanabe, Yoon-La Choi, Meraj Aziz, Michelle Kassner, Je-Gun Joung, Angela KJ Park, Joshua Francis, Joon Seol Bae, Soo-min Ahn, Kyoung-Mee Kim, Joon-Oh Park, Woong-Yang Park, Myung-Ju Ahn, Keunchil Park, Hongwei Holly Yin, Jeonghee Cho. Integrated genomic approaches identify upregulation of SCRN1 as a novel mechanism associated with acquired resistance to erlotinib in non small cell lung cancer cells with oncogenic EGFR mutation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2931.

Abstract LB-91: Identification and feasibility test of novel methylation biomarkers for stool DNA-based colorectal cancer screening

Aberrant DNA methylation event is known to be early and frequent process in tumorigenesis and could therefore serve as a convenient biomarker for early detection of cancers. For the identification of novel methylation markers we compared each methylation profiles in super normal tissues (n=2) of healthy individuals and primary tumors and their matched normal appearing adjacent tissues (non-tumor) from colorectal cancer patients (n=12) relative to that of common reference DNA through genome-wide CpG microarray analysis following methylated DNA enrichment with a minimum size of methyl binding domain. Unsupervised hierarchical clustering of with entire methylation pattern data successfully discriminated normal, match-paired normal and primary tumors. We then statistically selected novel methylation candidates showing high frequency of methylation in primary tumor samples and intermediate in non-tumor but no methylation in supernormal tissues for early detection and confirmed in colorectal cancer cell lines by quantitative pyrosequencing-based methylation assay. For final candidates with high specificity, we selected 4 genes, GABRA1, gt-SD, gt-SI, gt-SO which showed a low methylation level in 2 healthy normal tissues. All of 4 genes appeared to be much more frequently hypermethylated in primary tumors than in non-tumor tissues in pyrosequencing assay. For the applicability into non-invasive sample we analyzed methylation status of 4 genes in stool DNAs obtained from patients with colorectal cancer (n=106) and healthy volunteers (n=10) by modified two-round nested MSP for improving analytic sensitivity. The sensitivity and specificity of each of 4 genes were estimated as 50.5% to 60.2% and 85.7% to 100%, respectively. The sensitivity of the four-gene panel was 88.7% (94/106) and its specificity was 80.0% (2/10) in detecting colorectal cancer with stool DNA. Consequently, 4 novel genes have a great potential in noninvasive stool DNA testing for colorectal cancer screening. Further large-scale clinical validation will be needed for clinical setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-91.