Seok Jong Yu

Novel inhibitory function of miR-125b in melanogenesis

MicroRNAs are known to be the important regulators of skin physiology and considered as new therapeutic targets to treat skin diseases. In this study, miR‐125b was identified as a potent regulator of steady‐state melanogenesis. We found that the expression of miR‐125b was inversely related to pigment levels. A miR‐125b mimic decreased the expression of pigmentation‐related gene and melanin content, implying that miR‐125b functions to decrease pigmentation. Moreover, we observed that the reduction in miR‐125b expression in pigmented cells was at least partially due to the hypermethylation of the MIR125B‐1 promoter, and miR‐125b expression was regulated by intracellular cAMP levels.

S100A7 (psoriasin) inhibits human epidermal differentiation by enhanced IL‐6 secretion through IκB/NF‐κB signalling

Psoriasin (S100A7), a member of the S100 protein family, is a well‐known antimicrobial peptide and a signalling molecule which regulates cellular function and is highly expressed in hyperproliferative skin conditions such as atopic dermatitis (AD) and psoriasis with disrupted skin barrier function. However, its role in epidermal differentiation remains unknown. We examined the effect of S100A7 on epidermal differentiation in normal human keratinocytes (NHKs) and on a reconstituted human epidermis model. When NHKs were exposed to disruptive stimuli such as Staphylococcus aureus, ultraviolet irradiation and retinoic acid, the secretion of S100A7 into the culture medium increased and the expression of epidermal differentiation markers decreased. Treatment of NHKs with S100A7 significantly inhibited epidermal differentiation by reducing the expression of keratin 1, keratin 10, involucrin and loricrin and by increasing the expression of abnormal differentiation markers (keratin 6 and keratin 16). We verified that the MyD88‐IκB/NF‐κB signal cascade was activated via RAGE after S100A7 treatment, resulting in the upregulation of interleukin‐6. Finally, we confirmed that S100A7 is a negative regulator of epidermal differentiation using a reconstituted human epidermis model. This study suggests that S100A7‐related signalling molecules could be potent targets for recovering skin barrier function in AD and psoriasis where S100A7 is accumulated excessively.

ΔNp63 intronic miR-944 is implicated in the ΔNp63-mediated induction of epidermal differentiation.

ΔNp63 is required for both the proliferation and differentiation of keratinocytes, but its role in the differentiation of these cells is poorly understood. The corresponding gene, TP63, harbors the MIR944 sequence within its intron. However, the mechanism of biogenesis and the function of miR-944 are unknown. We found that miR-944 is highly expressed in keratinocytes, in a manner that is concordant with that of ΔNp63 mRNA, but the regulation of miR-944 expression under various conditions did not correspond with that of ΔNp63. Bioinformatics analysis and functional studies demonstrated that MIR944 has its own promoter. We demonstrate here that MIR944 is a target of ΔNp63. Promoter analysis revealed that the activity of the MIR944 promoter was markedly enhanced by the binding of ΔNp63, which was maintained by the supportive action of AP-2 during keratinocyte differentiation. Our results indicated that miR-944 biogenesis is dependent on ΔNp63 protein, even though it is generated from ΔNp63 mRNA-independent transcripts. We also demonstrated that miR-944 induces keratin 1 and keratin 10 expression by inhibiting ERK signaling and upregulating p53 expression. Our findings suggested that miR-944, as an intronic miRNA and a direct target of ΔNp63, contributes to the function of ΔNp63 in the induction of epidermal differentiation.

Development of Network Analysis and Visualization System for KEGG Pathways

Big data refers to informationalization technology for extracting valuable information through the use and analysis of large-scale data and, based on that data, deriving plans for response or predicting changes. With the development of software and devices for next generation sequencing, a vast amount of bioinformatics data has been generated recently. Also, bioinformatics data based big-data technology is rising rapidly as a core technology by the bioinformatician, biologist and big-data scientist. KEGG pathway is bioinformatics data for understanding high-level functions and utilities of the biological system. However, KEGG pathway analysis requires a lot of time and effort because KEGG pathways are high volume and very diverse. In this paper, we proposed a network analysis and visualization system that crawl user interest KEGG pathways, construct a pathway network based on a hierarchy structure of pathways and visualize relations and interactions of pathways by clustering and selecting core pathways from the network. Finally, we construct a pathway network collected by starting with an Alzheimer’s disease pathway and show the results on clustering and selecting core pathways from the pathway network.

Accelerating Genome Sequence Alignment on Hadoop on Lustre Environment

Genome sequence alignment is one of the basic procedure of genome sequencing analysis pipeline and also one of the most time-consuming parts. Including BigBWA, a number of tools were proposed to accelerate genome sequence alignment by parallelizing computation with Hadoop technologies. However, HDFS incurs considerable I/O overhead. In this research, we propose a new sequence alignment tool adopting Hadoop on Lustre. Based on BigBWA, we removed data transfer overhead caused by HDFS and parallelized whole I/O steps. Experimental result shows that our solution is five times faster than original BigBWA in a ten-node Lustre based Hadoop cluster.

Implementing Biological Network Analysis System through Oriental Medical Literature Analysis

최근 한의학에 대한 과학적 접근이 진행되면서 한약재 성분의 효능을 검증하고자 하는 다양한 분자 생물 학 분야의 연구가 진행되고 있다. 하지만 관련 한약재의 주요 성분과 관련된 생화학적 기작을 손쉽게 검색 할 수 있는 시스템이 갖추어져 있지 못한 실정이다. 본 연구는 국내 한약재에 대한 약효 성분과 생물학적 기작에 대한 정보를 수집 및 텍스트마이닝을 수행하여 한약재 정보 데이터베이스를 구축하고자 하였다. 연구자가 손쉽게 분석된 한약재의 화합물, 유전자 그리고 생물학적 상호작용 정보를 검색할 수 있는 웹사 이트 원형을 개발하였다. 문헌 분석결과 한의학분야 주요 화합물 및 유전자/단백질 정보를 추출할 수 있었 고 현대 한의학 연구 현황의 특징을 보여주었다. 분석된 결과는 웹을 통해 한약재별 PubMed 문헌 정보와 관련된 한약재의 약재 정보 및 생물학적 상호작용 정보를 가시화하여 볼 수 있도록 개발하였다.

Network Comparison of Inflammation in Colorectal Cancer and Alzheimer’s Disease

Recently, a large clinical study revealed an inverse correlation of individual risk of cancer versus Alzheimers disease (AD). However, no explanation exists for this anticorrelation at the molecular level; however, inflammation is crucial to the pathogenesis of both diseases, necessitating a need to understand differing signaling usage during inflammatory responses distinct to both diseases. Using a subpathway analysis approach, we identified numerous well-known and previously unknown pathways enriched in datasets from both diseases. Here, we present the quantitative importance of the inflammatory response in the two disease pathologies and summarize signal transduction pathways common to both diseases that are affected by inflammation.