약물-질병 경로 네트워크의 구축과 비교를 통한 신약재창출

황소윤(Soyoun Hwang),황유현(Youhyeon Hwang),오민(Min Oh),윤영미(Youngmi Yoon) 한국정보기술학회 2016 한국정보기술학회논문지 Vol.14 No.9

As genome data are continuously increasing, there have been various efforts that elucidate a mechanism of drug action. However, the mechanism of drug action is still not elucidated perfectly despite various previous efforts. In this paper, we constructed drug-disease gene network based on protein-protein interaction to better understand a mechanism of drug action, and applied drug repositioning. In order to construct pathway networks for drug-disease pairs, we connected the drug target genes, drug related genes and the disease related genes respectively. We extracted critical gene networks for particular drug-disease pairs of which therapeutic indications are known. By estimating similarity between the critical gene networks and candidate networks derived from drug-disease pairs whose therapeutic effects are unknown, new drug indications were predicted. The putative drug indications significantly overlapped with those of CTD database (Fishers exact P = 7.01E-104). In performance evaluation, the prediction result showed the area under the ROC curve (AUC) of 0.7122.

Selection and elution of aptamers using nanoporous sol-gel arrays with integrated microheaters

Park, Seung-min,Ahn, Ji-Young,Jo, Minjoung,Lee, Dong-ki,Lis, John T.,Craighead, Harold G.,Kim, Soyoun Royal Society of Chemistry 2009 Lab on a chip Vol.9 No.9

<P>RNA and DNA aptamers that bind to target molecules with high specificity and affinity have been a focus of diagnostics and therapeutic research. These aptamers are obtained by SELEX (Systematic Evolution of Ligands by EXponential enrichment) often requiring more than 10 successive cycles of selection and amplification, where each cycle normally takes 2 days per cycle of SELEX. Here, we have demonstrated the use of sol-gel arrays of proteins in a microfluidic system for efficient selection of RNA aptamers against multiple target molecules. The microfluidic chip incorporates five sol-gel binding droplets, within which specific target proteins are imbedded. The droplets are patterned on top of individually addressable electrical microheaters used for selective elution of aptamers bound to target proteins in the sol-gel droplets. We demonstrate that specific aptamers bind their respective protein targets and can be selectively eluted by micro-heating. Finally, our microfluidic SELEX system greatly improved selection efficiency, reducing the number of selection cycles needed to produce high affinity aptamers. The process is readily scalable to larger arrays of sol-gel-embedded proteins. To our knowledge, this is the first demonstration of a chip-based selection of aptamers using microfluidics, thereby allowing development of a high throughput and efficient SELEX procedures.</P> <P>Graphic Abstract</P><P>Sol-gel arrays of proteins in a microfluidic system for efficient selection of RNA aptamers against multiple target molecules <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b814993c'> </P>

정신건강복지법 개정에 따른 입원적합성심사와 관련된 이해관계자의 경험

신소연 ( Shin Soyoun ),조윤민 ( Cho Yoon-min ),윤난희 ( Yoon Nan-he ),황서은 ( Hwang Seo Eun ),황종남 ( Hwang Jongnam ),최정원 ( Choi Jung Won ),김잔디 ( Kim Jandi ),허종호 ( Heo Jongho ),이선구 ( Lee Sun Goo ) 한국보건사회연구원 2021 保健社會硏究 Vol.41 No.2

2016년, 구 정신보건법이 「정신건강증진 및 정신질환자 복지서비스 지원에 관한 법률」로 개정되면서, 입원적합성심사위원회(이하 입적심) 제도가 신설되고 비자의입원 절차가 강화되었다. 본 연구는 입적심의 목표인 정신질환자의 인권증진 여부를 평가하기 위해 이해관계자들의 참여경험을 질적으로 분석하고, 향후 나아갈 방안을 모색하였다. 이에 전국 5개 국립정신병원에서 입적심과 관련된 총 27명의 전문의, 법조인, 정신건강전문요원, 가족, 당사자, 조사원, 정신질환자를 심층 면담하였다. 주제분석 결과, 4개의 주제와 16개의 하위주제가 도출되었다. 입적심 제도는 부당한 비자의입원 및 강압 이송행위에 대한 안전장치를 마련하여 인권을 향상시켰지만, 대면조사보다 서류심사가 주를 이루고 의사결정지원이 미흡하여 자기결정권이 제한된다는 한계를 드러냈다. 추후 자기결정권을 보장하기 위한 대면조사와 절차보조사업을 확충하고, 의료기관과 지역사회서비스를 연결하는 협력시스템이 구축되어야 한다. The revision of the “Mental Health Act” into the “Act on the Improvement of Mental Health and the Support for Welfare Services for Mental Patients” in 2016 led to the tightening of procedures for involuntary hospitalization through the implementation of the “Committee for Review as to Legitimacy of Admission” (hereinafter “Admission Review Committee”). This study evaluated whether the Admission Review Committee has achieved its goal to promote the human rights of people with a mental illness through qualitative analysis of stakeholder experiences. The evaluation is based on interviews with a total of 27 subcommittee members from all the five national psychiatric hospitals which have an Admission Review Committee in place. Those interviewed were psychiatrists, lawyers, mental health professionals, patients and their families, and investigators. As a result, a total of four categories and 16 themes emerged from the thematic analysis. Our study shows that the Admission Review Committee has promoted human rights by functioning as a minimum safeguard to prevent unjust involuntary hospitalization and forced transfer to psychiatric hospitals. However, insufficient procedural assistance has limited the right to self-determination, and the committee heavily relied on paper review rather than the face-to-face investigation with people with a mental illness. For a better supportive committee for the human rights of people with a mental illness, we suggest that the committee adopt the face-to-face review process, procedural assistance services, and a governance system closely connecting medical facilities with local communities.

Existence of glioma stroma mesenchymal stemlike cells in Korean glioma specimens.

Kim, Young Goo,Jeon, Soyoun,Sin, Ga-Yeong,Shim, Jin-Kyoung,Kim, Bo-Kyung,Shin, Hye-Jin,Lee, Ji-Hyun,Huh, Yong-Min,Lee, Su-Jae,Kim, Eui-Hyun,Park, Eun Kyung,Kim, Se-Hoon,Chang, Jong Hee,Kim, Dong Seok Springer Verlag 2013 Child’s nervous system Vol.29 No.4

<P>It was presented that mesenchymal stem cells (MSCs) can be isolated from western glioma specimens. However, whether MSCs exist in glioma specimens of different ethnicities is unknown. To verify the existence of MSCs in an independent cohort, we undertook studies to isolate MSCs from a group of Korean patients. We hypothesized that cells resembling MSCs that were deemed mesenchymal stemlike cells (MSLCs) exist in an independent cohort of Korean gliomas. We cultured fresh glioma specimens using the protocols used for culturing MSCs. The cultured cells were analyzed with fluorescence-activated cell sorting (FACS) for surface markers associated with MSCs. Cultured cells were exposed to mesenchymal differentiation conditions. To presume possible locations of MSLCs in the glioma, sections of glioma were analyzed by immunofluorescent labeling for CD105, CD31, and NG2. From nine of 31 glioma specimens, we isolated cells resembling MSCs, which were deemed Korean glioma stroma MSLCs (KGS-MSLCs). KGS-MSLCs were spindle shaped and adherent to plastic. KGS-MSLCs had similar surface markers to MSCs (CD105(+), CD90(+), CD73(+), and CD45(-)). KGS-MSLCs were capable of mesenchymal differentiation and might be located around endothelial cells, pericytes, and in a disorganized perivascular area inside glioma stroma. We found that cells resembling MSCs indeed exist in an independent cohort of glioma patients, as presented in western populations. We could presume that the possible location of KGS-MSLCs was in perivascular area or in glioma stroma that was a disorganized vascular niche. It might be possible that KGS-MSLCs could be one of constituent of stroma of glioma microenvironment.</P>

Microphysiological Engineering of Immune Responses in Intestinal Inflammation

Yoko M. Ambrosini,Woojung Shin,Soyoun Min,Hyun Jung Kim 대한면역학회 2020 Immune Network Vol.20 No.2

Phosphorylation of the RNA polymerase II C-terminal domain by TFIIH kinase is not essential for transcription of Saccharomyces cerevisiae genome.

Hong, Sun Woo,Hong, Seong Min,Yoo, Jae Wook,Lee, Young Chul,Kim, Soyoun,Lis, John T,Lee, Dong-Ki National Academy of Sciences 2009 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.106 No.34

<P>Ser-5 phosphorylation of the RNA polymerase II (Pol II) C-terminal domain by TFIIH kinase has been implicated in critical steps in mRNA synthesis, such as Pol II promoter escape and mRNA 5'-capping. However, the general requirement and precise role of TFIIH kinase in Pol II transcription still remain elusive. Here we use a chemical genetics approach to show that, for a majority of budding-yeast genes, specific inhibition of the yeast TFIIH kinase results in a dramatic reduction in both mRNA level and Ser-5 C-terminal domain phosphorylation. Surprisingly, inhibition of TFIIH kinase activity only partially affected both Pol II density and Ser-2 phosphorylation level. The discrepancy between mRNA level and Pol II density is attributed to the defective 5'-capping, which results in the destabilization of mRNAs. Therefore, contrary to the current belief, our study points strongly toward a minor role of TFIIH kinase in Pol II transcription, and a more significant role in mRNA capping in budding yeast.</P>

Microphysiological Engineering of Immune Responses in Intestinal Inflammation

Yoko M. Ambrosini,Woojung Shin,Soyoun Min,Hyun Jung Kim 대한면역학회 2020 Immune Network Vol.20 No.2

The epithelial barrier in the gastrointestinal (GI) tract is a protective interface that endures constant exposure to the external environment while maintaining its close contact with the local immune system. Growing evidence has suggested that the intercellular crosstalk in the GI tract contributes to maintaining the homeostasis in coordination with the intestinal microbiome as well as the tissue-specific local immune elements. Thus, it is critical to map the complex crosstalks in the intestinal epithelial-microbiome-immune (EMI) axis to identify a pathological trigger in the development of intestinal inflammation, including inflammatory bowel disease. However, deciphering a specific contributor to the onset of pathophysiological cascades has been considerably hindered by the challenges in current in vivo and in vitro models. Here, we introduce various microphysiological engineering models of human immune responses in the EMI axis under the healthy conditions and gut inflammation. As a prospective model, we highlight how the human “gut inflammation-on-a-chip” can reconstitute the pathophysiological immune responses and contribute to understanding the independent role of inflammatory factors in the EMI axis on the initiation of immune responses under barrier dysfunction. We envision that the microengineered immune models can be useful to build a customizable patient's chip for the advance in precision medicine.

Label-free Detection of the Transcription Initiation Factor Assembly and Specific Inhibition by Aptamers

Ren, Shuo,Jiang, Yuanyuan,Yoon, Hye Rim,Hong, Sun Woo,Shin, Donghyuk,Lee, Sangho,Lee, Dong-Ki,Jin, Moonsoo M.,Min, Irene M.,Kim, Soyoun Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.5

The binding of TATA-binding protein (TBP) to the TATA-box containing promoter region is aided by many other transcriptional factors including TFIIA and TFIIB. The mechanistic insight into the assembly of RNA polymerase II preinitation complex (PIC) has been gained by either directly altering a function of target protein or perturbing molecular interactions using drugs, RNAi, or aptamers. Aptamers have been found particularly useful for studying a role of a subset of PIC on transcription for their ability to inhibit specific molecular interactions. One major hurdle to the wide use of aptamers as specific inhibitors arises from the difficulty with traditional assays to validate and determine specificity, affinity, and binding epitopes for aptamers against targets. Here, using a technique called the bio-layer interferometry (BLI) designed for a label-free, real-time, and multiplexed detection of molecular interactions, we studied the assembly of a subset of PIC, TBP binding to TATA DNA, and two distinct classes of aptamers against TPB in regard to their ability to inhibit TBP binding to TFIIA or TATA DNA. Using BLI, we measured not only equilibrium binding constants ($K_D$), which were overall in close agreement with those obtained by electrophoretic mobility shift assay, but also kinetic constants of binding ($k_{on}$ and $k_{off}$), differentiating aptamers of comparable KDs by their difference in binding kinetics. The assay developed in this study can readily be adopted for high throughput validation of candidate aptamers for specificity, affinity, and epitopes, providing both equilibrium and kinetic information for aptamer interaction with targets.