https://scholar.dgist.ac.kr/handle/20.500.11750/11719 2026-05-21T21:46:35Z 2026-05-21T21:46:35Z Han, Bitnara Lim, Hyun Ji Kim, Su-Jung Shin, Jaejin Kim, Hyeong Hwan Kim, Kyun-Hwan Nam, Chang-Hoon Kim, Kwang Pyo https://scholar.dgist.ac.kr/handle/20.500.11750/60337 2026-05-06T18:01:18Z 2026-01-31T15:00:00Z

Title: Proteomics and phosphoproteomics of human colorectal cancer cells lacking a specific kinase activity reveal kinase-specific compensatory responses Author(s): Han, Bitnara; Lim, Hyun Ji; Kim, Su-Jung; Shin, Jaejin; Kim, Hyeong Hwan; Kim, Kyun-Hwan; Nam, Chang-Hoon; Kim, Kwang Pyo Abstract: Cell signaling regulates cell proliferation, survival, and migration, and abnormal kinase activity is often implicated in cancer. Although kinases are key targets for anticancer therapy, drug-induced compensatory signaling and pathway rewiring often drive acquired resistance. These compensatory responses enable tumor cells to maintain proliferation and survival, contributing to acquired drug resistance. In this study, we investigated adaptive responses following the knockout of four specific kinase genes, ERK2, PLK1, PIK3CA, and PAK4, using HCT-116, a human colorectal cancer cell line. Using CRISPR-Cas9, we generated individual knockout cell lines and conducted quantitative proteomic and phosphoproteomic profiling using isobaric tagging and tandem mass tag (TMTs) to evaluate alterations in the signaling landscape. Our integrated analysis quantified 7,531 proteins and 10,877 phosphopeptides, revealing kinase-specific patterns of compensatory signaling. ERK2 knockout was associated with activation of MAPK- and PI3K/AKT-related kinases, whereas PIK3CA knockout induced extensive proteomic remodeling and engagement of pro-survival phosphorylation programs, illustrating distinct modes of signaling network rewiring. Integration of kinase-substrate enrichment analysis (KSEA) with global proteomic data revealed that adaptive kinase activity was largely uncoupled from protein abundance and uncovered a synthetic lethal interaction between ERK2 loss and RPS6KB1 inhibition. Collectively, these findings elucidate how targeted kinase loss drives homeostatic signaling networks in cancer cells. By systemically characterizing cellular-level signaling changes and contextualizing them within known kinase pathways, our results provide insights into synthetic lethality and identify potential therapeutic targets to counteract adaptive resistance to kinase inhibitors.

2026-01-31T15:00:00Z Kim, Hwapyong Kim, Ki Nam Lee, Sang-Hyeon Nam, Chang-Hoon Lee, Young-Sam In, Su-Il https://scholar.dgist.ac.kr/handle/20.500.11750/59989 2026-02-09T18:01:18Z 2025-12-31T15:00:00Z

Title: Hydrogen Evolution via Oxygen Tolerant [NiFe]-Hydrogenase Immobilized on TiO2 Nanotubes Author(s): Kim, Hwapyong; Kim, Ki Nam; Lee, Sang-Hyeon; Nam, Chang-Hoon; Lee, Young-Sam; In, Su-Il Abstract: [FeFe]-hydrogenase has been of great interest due to its high enzymatic activity for hydrogen evolution reactions (HERs). However, the big challenge of [FeFe]-hydrogenase is a significant performance degradation in aerobic conditions. On the other hand, [NiFe]-hydrogenase of E. coli has an oxygen tolerant property. Therefore, using [NiFe]-hydrogenase is an effective solution to avoid performance degradation in aerobic conditions. Herein, we extracted [NiFe]-hydrogenases from E. coli and immobilized them on the TiO2 nanotube (TNT) electrode prepared by pyrrole-based electropolymerization for application in aerobic conditions. As a result, we can confirm that [NiFe]-hydrogenases coated TNT electrode demonstrates the increased HER activity underaerobic condition than control samples in in-vitro activity test using methylene viologen and linear sweep voltammetry.

2025-12-31T15:00:00Z Heo, Jin-Woong Kim, Hyeong Hwan Lee, Jae Ho Lee, Hyeong Min Park, Hyung Soon Nam, Chang-Hoon https://scholar.dgist.ac.kr/handle/20.500.11750/59369 2026-02-25T06:40:13Z 2025-10-31T15:00:00Z

Title: Targeting PON2 with Vutiglabridin Restores Mitochondrial Integrity and Attenuates Oxidative Stress-Induced Senescence Author(s): Heo, Jin-Woong; Kim, Hyeong Hwan; Lee, Jae Ho; Lee, Hyeong Min; Park, Hyung Soon; Nam, Chang-Hoon Abstract: Oxidative stress-induced mitochondrial dysfunction has been identified as a central driver of cellular senescence and age-related degeneration. The present study investigated the potential of vutiglabridin, a paraoxonase 2 (PON2) agonist, to mitigate reactive oxygen species (ROS)-induced senescence in human LO2 hepatocytes. The process of senescence was induced by the administration of hydrogen peroxide, followed by the recovery of the cells in fresh medium. The levels of intracellular ROS, the senescence-associated β-galactosidase staining, the p16/p21 expression, and the mitochondrial morphology were the focus of a comprehensive assessment utilizing a range of analytical techniques, including microscopy, quantitative PCR, and Western blotting. The present study demonstrated that the administration of vutiglabridin resulted in a dose-dependent reduction in attenuation of the expression of senescence markers. Transmission electron microscopy (TEM) and stimulated emission depletion (STED) imaging revealed the preservation of mitochondrial structure and network connectivity in cells treated with vutiglabridin. These effects were absent in PON2 knockout cells, confirming that vutiglabridin’s action requires functional PON2. The present study demonstrates that vutiglabridin alleviates oxidative stress-induced cellular senescence by preserving mitochondrial integrity and redox balance via a PON2-dependent mechanism. This study lends further support to the investigation of the PON2 pathway as a therapeutic target in age-related cellular dysfunction.

2025-10-31T15:00:00Z Kim, Jihyun Lee, Jieun Kang, Eunho Lee, Kyoungmin Lee, Kyungeun Cheon, Yeongmi Lee, Seongsoo Kim, Bokyung Ko, Young Ho Kim, Jin Hae In, Su Il Nam, Chang-Hoon https://scholar.dgist.ac.kr/handle/20.500.11750/57266 2025-07-25T02:42:29Z 2024-12-31T15:00:00Z

Title: Insights into an indolicidin-derived low-toxic anti-microbial peptide's efficacy against bacterial cells while preserving eukaryotic cell viability Author(s): Kim, Jihyun; Lee, Jieun; Kang, Eunho; Lee, Kyoungmin; Lee, Kyungeun; Cheon, Yeongmi; Lee, Seongsoo; Kim, Bokyung; Ko, Young Ho; Kim, Jin Hae; In, Su Il; Nam, Chang-Hoon Abstract: Antimicrobial peptides (AMPs) are a current solution to combat antibiotic resistance, but they have limitations, including their expensive production process and the induction of cytotoxic effects. We have developed novel AMP candidate (peptide 3.1) based on indolicidin, among the shortest naturally occurring AMP. The antimicrobial activity of this peptide is demonstrated by the minimum inhibitory concentration, while the hemolysis tests and MTT assay indicate its low cytotoxicity. In optical diffraction tomography, red blood cells treated with peptide 3.1 showed no discernible effects, in contrast to indolicidin. However, peptide 3.1 did induce cell lysis in E. coli, leading to a reduced potential for the development of antibiotic resistance. To investigate the mechanism underlying membrane selectivity, the structure of peptide 3.1 was analyzed using nuclear magnetic resonance spectroscopy and molecular dynamics simulations. Peptide 3.1 is structured with an increased distinction between hydrophobic and charged residues and remained in close proximity to the eukaryotic membrane. On the other hand, peptide 3.1 exhibited a disordered conformation when approaching the prokaryotic membrane, similar to indolicidin, leading to its penetration into the membrane. Consequently, it appears that the amphipathicity and structural rigidity of peptide 3.1 contribute to its membrane selectivity. In conclusion, this study may lead to the development of Peptide 3.1, a promising commercial candidate based on its low cost to produce and low cytotoxicity. We have also shed light on the mechanism of action of AMP, which exhibits selective toxicity to bacteria while not damaging eukaryotic cells. © 2024 International Union of Biochemistry and Molecular Biology.

2024-12-31T15:00:00Z