https://scholarworks.unist.ac.kr/handle/201301/1 2026-04-17T22:54:25Z https://scholarworks.unist.ac.kr/handle/201301/91350 Title: BCR::ABL1 tyrosine kinase inhibitors induce ribosome collisions to activate ZAK-dependent ribotoxic stress and apoptosis in chronic myeloid leukemia Author(s): Park, Jumin; Kim, Soo-Hyun; Park, Jongmin; Park, Heeju; Kim, Hongtae; Kim, Dong-Wook; Lim, Chunghun Abstract: Ribosome collisions act as molecular sensors of cellular stress, yet their role in disease physiology remains unclear. Here, we demonstrate that inhibition of the oncogenic kinase BCR::ABL1 in chronic myeloid leukemia (CML) cells induces ribosome collisions and activates the ribotoxic stress response (RSR). Clinical analyses revealed that CML progression from the chronic phase to the aggressive blast phase correlated with elevated expression of the RSR-initiating kinase ZAK. Although ZAK sustained CML cell proliferation by promoting AKT activity, loss of ZAK function paradoxically reduced the cytotoxic effects of BCR::ABL1 inhibitors. Mechanistically, BCR::ABL1 inhibition promoted phosphorylation of eukaryotic translation elongation factor 2 (EEF2) via the mTOR-EEF2K pathway, slowed translation elongation, and generated nuclease-resistant collided ribosomes that triggered ZAK-dependent p38 activation and apoptosis. Furthermore, pharmacological modulation of translation flux fine-tuned the efficacy of BCR::ABL1 inhibitors, including in primary patient cells. These findings define a ribosome-based stress pathway crucial for CML apoptosis and highlight ZAK-dependent RSR as a therapeutic vulnerability. 2026-02-28T15:00:00Z https://scholarworks.unist.ac.kr/handle/201301/91347 Title: Leukemia-Targeting NK cell Nanoengagers Effectively Promote Robust NK Activation and Potent Anti-Acute Myeloid Leukemia Response Author(s): Kim, Hyo Jeong; Jun, Heejin; Lee, Hyun Bin; Eom, Soomin; Kim, Junsu; Jeon, Jun Pyo; Park, Sung Ho; Kang, Sebyung Abstract: Natural killer (NK) cells are key components of innate immunity, playing a pivotal role in tumor recognition and eradication, and numerous NK cell-based immunotherapeutic approaches have been extensively investigated for cancer treatment. Here, we develop leukemia-targeting NK cell nanoengagers, termed AaLS/aCD16Nb/aCD13Nb, by simultaneously displaying NK cell-engaging nanobodies (aCD16Nb) and acute myeloid leukemia (AML)-targeting nanobodies (aCD13Nb) on lumazine synthase (AaLS) protein nanoparticles. The AaLS/aCD16Nb/aCD13Nb nanoengagers effectively bind to both NK cells and AML cells, thereby facilitating selective engagement of NK cells with leukemic targets. Through this targeted engagement, the AaLS/aCD16Nb/aCD13Nb nanoengagers promote NK cell activation, leading to enhanced interferon gamma (IFN-γ) production and robust AML cell killing in vitro. Furthermore, in AML-engraft mouse models, administration of the AaLS/aCD16Nb/aCD13Nb nanoengagers significantly reduce leukemic burden across multiple tissues, with pronounced effects in the bone marrow niche, and extend overall survival in two independent AML (U937 and THP-1) engrafted models. Collectively, our study demonstrates that this dual-ligand-displaying nanoengager platform represents a promising and potent anti-leukemic strategy, offering a multifunctional protein nanoparticles-based approach for AML immunotherapy that may be broadly adaptable to other malignancies. 2026-03-31T15:00:00Z https://scholarworks.unist.ac.kr/handle/201301/91274 Title: Antiplatelet activity of a Korean red ginseng–derived saponin fraction and its inhibition of influenza A virus–induced thrombosis Author(s): Lee, Ga Hee; Oh, Jueun; Lee, Jin Pyo; Heo, Na Yoon; Lee, SangJoon; Lee, Dong-Ha Abstract: Background: Platelets play a central role in thrombus formation, which is a major cause of morbidity and mortality worldwide. Viral infections have been reported to further promote thrombus formation, posing a critical risk in unpredictable pandemic situations. Therefore, we evaluated whether a Korean red ginseng–derived saponin fraction could serve as a safe and effective antithrombotic agent by assessing its inhibitory effects. Methods: Human platelets were examined using an aggregometer, flow cytometry, fluorescence assays, ELISA kits, and western blotting to assess cGMP, intracellular Ca2+ levels, fibrinogen binding, granule secretion (ATP and serotonin), and phosphorylation of IP3R, VASP, MAPKs, PI3K/Akt, and cPLA2. Thrombin-induced clot retraction was quantified. The in vivo effects were further evaluated in influenza A virus (IAV)-infected mice using a FeCl3-induced carotid artery thrombosis model, where thrombus formation and blood flow were monitored. Results: The saponin fraction markedly inhibited platelet aggregation, enhanced cGMP production, and increased phosphorylation of IP3R and VASP Ser239. Conversely, it suppressed phosphorylation of MAPKs (JNK and p38), PI3K/Akt, and cPLA2, thereby blocking downstream signaling pathways. In vivo, IAV infection accelerated thrombus formation and reduced blood flow, whereas administration of the saponin fraction significantly attenuated these pathological changes. Conclusion: The saponin fraction effectively suppressed platelet activation in vitro and thrombus formation in vivo, even under virus-induced prothrombotic conditions. These findings suggest that the saponin fraction has potential as a safe and effective natural antithrombotic agent. 2025-12-31T15:00:00Z https://scholarworks.unist.ac.kr/handle/201301/91250 Title: Fucoxanthin Extracted from the Microalgae Phaeodactylum tricornutum Ameliorates Alzheimer's Pathologies with the Reduction of Aβ-Induced NLRP3 Inflammasome Activation in APP/PS1 Mice Author(s): Ahn Na-Hyun; Hong Sung-Chul; Hong Chi Rac; Lee Eun Ha; Lee Joo-Hee; Choi Su-Bin; Jung Jaewoon; Kim Yebeen; Kim, Jung-Seok; Park Keunwan; Kim Yun Kyung; Kim Youngsoo; Yang Seung-Hoon Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder, one of the most common types of dementia, accompanying severe learning and memory dysfunctions. In AD brains, the misfolded aggregation and deposits of amyloid-beta (A beta) and tau are frequently observed before the cognitive symptom onset; thus, trials for alleviation of these lesions are considered commensurate strategies with AD treatment. Additionally, increasing evidence suggests that misfolded and aggregated proteins induce the activation of microglia and astrocytes by the release of the inflammatory mediators via the activation of the inflammatory signaling cascade, which consequently contributes to AD pathogenesis. Here, we investigated the therapeutic potential of fucoxanthin, a compound derived from the microalgae Phaeodactylum tricornutum, in mitigating AD pathologies. Fucoxanthin was shown to inhibit the aggregation of A beta and tau, converting their aggregates to monomeric forms. In the brain of APP/PS1 transgenic mice, fucoxanthin administration significantly reduced the levels of A beta plaques and hyperphosphorylated tau and further ameliorated cognitive impairments by inhibiting the activation of microglia and astrocytes. Notably, fucoxanthin effectively regulated A beta-induced NLRP3 inflammasome activation in astrocytes, reducing neuroinflammation associated with AD. Thus, our findings showing the multifaceted therapeutic mode of action of fucoxanthin against AD provide that fucoxanthin would have promising roles in the strategies of AD treatment. 2025-12-31T15:00:00Z