https://scholar.dgist.ac.kr/handle/20.500.11750/335 2026-04-04T19:03:59Z https://scholar.dgist.ac.kr/handle/20.500.11750/56374 Title: Proteomics in Rheumatoid Arthritis Research Author(s): Park, Yune-Jung; Chung, Min Kyung; Hwang, Dae Hee; Kim, Wan-Uk Abstract: Although rheumatoid arthritis (RA) is the most common chronic inflammatory autoimmune disease, diagnosis of RA is currently based on clinical manifestations, and there is no simple, practical assessment tool in the clinical field to assess disease activity and severity. Recently, there has been increasing interest in the discovery of new diagnostic RA biomarkers that can assist in evaluating disease activity, severity, and treatment response. Proteomics, the largescale study of the proteome, has emerged as a powerful technique for protein identification and characterization. For the past 10 years, proteomic techniques have been applied to different biological samples (synovial tissue/fluid, blood, and urine) from RA patients and experimental animal models. In this review, we summarize the current state of the application of proteomics in RA and its importance in identifying biomarkers and treatment targets. 2015-07-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/12669 Title: Statistical Modeling for Enhancing the Discovery Power of Citrullination from Tandem Mass Spectrometry Data Author(s): Huh, Sunghyun; Hwang, Daehee; Kim, Min-Sik Abstract: Citrullination is a post-translational modification implicated in various human diseases including rheumatoid arthritis, Alzheimer's disease, multiple sclerosis, and cancers. Due to a relatively low concentration of citrullinated proteins in the total proteome, confident identification of citrullinated proteome is challenging in mass spectrometry (MS)-based proteomic analysis. From these MS-based analyses, MS features that characterize citrullination, such as immonium ions (IMs) and neutral losses (NLs), called diagnostic ions, have been reported. However, there has been a lack of systematic approaches to comprehensively search for diagnostic ions and no statistical methods for the identification of citrullinated proteome based on these diagnostic ions. Here, we present a systematic approach to identify diagnostic IMs, internal ions (INTs), and NLs for citrullination from tandem mass (MS/MS) spectra. Diagnostic INTs mainly consisted of internal fragment ions for di- and tripeptides that contained two and three amino acids with at least one citrullinated arginine, respectively. A statistical logistic regression model was built for a confident assessment of citrullinated peptides that database searches identified (true positives) and prediction of citrullinated peptides that database searches failed to identify (false negatives) using the diagnostic IMs, INTs, and NLs. Applications of our model to complex global proteome data sets demonstrated the increased accuracy in the identification of citrullinated peptides, thereby enhancing the size and functional interpretation of citrullinated proteomes. Copyright © 2020 American Chemical Society. 2020-09-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/11653 Title: Regulation of stomatal development by stomatal lineage miRNAs Author(s): Zhu, Jiali; Park, Ji-Hwan; Lee, Seulbee; Lee, Jae Ho; Hwang, Daehee; Kwak, June Myoung; Kim, Yun Ju Abstract: Stomata in the plant epidermis play a critical role in growth and survival by controlling gas exchange, transpiration, and immunity to pathogens. Plants modulate stomatal cell fate and patterning through key transcriptional factors and signaling pathways. MicroRNAs (miRNAs) are known to contribute to developmental plasticity in multicellular organisms; however, no miRNAs appear to target the known regulators of stomatal development. It remains unclear as to whether miRNAs are involved in stomatal development. Here, we report highly dynamic, developmentally stage-specific miRNA expression profiles from stomatal lineage cells. We demonstrate that stomatal lineage miRNAs positively and negatively regulate stomatal formation and patterning to avoid clustered stomata. Target prediction of stomatal lineage miRNAs implicates potential cellular processes in stomatal development. We show that miR399-mediated PHO2 regulation, involved in phosphate homeostasis, contributes to the control of stomatal development. Our study demonstrates that miRNAs constitute a critical component in the regulatory mechanisms controlling stomatal development. © 2020 National Academy of Sciences. All rights reserved. 2020-02-29T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/10961 Title: CCN1 interlinks integrin and hippo pathway to autoregulate tip cell activity Author(s): Park, Myo-Hyeon; Kim, Ae kyung; Manandhar, Sarala; Oh, Su-Young; Jang, Gun-Hyuk; Kang, Li; Lee, Dong-Won; Hyeon, Do Young; Lee, Sun-Hee; Lee, Hye Eun; Huh, Tae-Lin.; Suh, Sang Heon.; Hwang, Daehee; Byun, Kyunghee; Park, Hae-Chul; Lee, You Mie Abstract: CCN1 (CYR61) stimulates active angiogenesis in various tumours, although the mechanism is largely unknown. Here, we report that CCN1 is a key regulator of endothelial tip cell activity in angiogenesis. Microvessel networks and directional vascular cell migration patterns were deformed in ccn1-knockdown zebrafish embryos. CCN1 activated VEGFR2 and downstream MAPK/PI3K signalling pathways, YAP/TAZ, as well as Rho effector mDia1 to enhance tip cell activity and CCN1 itself. VEGFR2 interacted with integrin αvβ3 through CCN1. Integrin αvβ3 inhibitor repressed tip cell number and sprouting in postnatal retinas from endothelial cell-specific Ccn1 transgenic mice, and allograft tumours in Ccn1 transgenic mice showed hyperactive vascular sprouting. Cancer patients with high CCN1 expression have poor survival outcomes and positive correlation with ITGAV and ITGB3 and high YAP/WWTR1. Thus, our data underscore the positive feedback regulation of tip cells by CCN1 through integrin αvβ3/VEGFR2 and increased YAP/TAZ activity, suggesting a promising therapeutic intervention for pathological angiogenesis. © 2019, Park et al. 2019-07-31T15:00:00Z