https://scholarworks.unist.ac.kr/handle/201301/8 2026-05-13T13:13:51Z https://scholarworks.unist.ac.kr/handle/201301/91694 Title: Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy Author(s): Jang, Hyun-Jun; Lee, Yo Han; Tam, Dao; Jo, Yunju; Khim, Keon Woo; Eom, Hye-jin; Lee, Ju Eun; Song, Yi Jin; Choi, Sun Sil; Park, Kieun; Ji, Haneul; Chae, Young Chan; Myung, Kyungjae; Kim, Hongtae; Ryu, Dongryeol; Park, Neung Hwa; Park, Sung Ho; Choi, Jang Hyun Abstract: Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment. 2023-07-31T15:00:00Z https://scholarworks.unist.ac.kr/handle/201301/91693 Title: PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin III Author(s): Kim, Hye Yun; Lee, Jieun; Kim, Hyun-Jin; Lee, Byeong Eun; Jeong, Jaewook; Cho, Eun Jeong; Jang, Hyun-Jun; Shin, Kyeong Jin; Kim, Min Ji; Chae, Young Chan; Lee, Seung Eun; Myung, Kyungjae; Baik, Ja-Hyun; Suh, Pann-Ghill; Kim, Jae-Ick Abstract: Dopamine neurons are essential for voluntary movement, reward learning, and motivation, and their dysfunction is closely linked to various psychological and neurodegenerative diseases. Hence, understanding the detailed signaling mechanisms that functionally modulate dopamine neurons is crucial for the development of better therapeutic strategies against dopamine-related disorders. Phospholipase Cγ1 (PLCγ1) is a key enzyme in intracellular signaling that regulates diverse neuronal functions in the brain. It was proposed that PLCγ1 is implicated in the development of dopaminergic neurons, while the physiological function of PLCγ1 remains to be determined. In this study, we investigated the physiological role of PLCγ1, one of the key effector enzymes in intracellular signaling, in regulating dopaminergic function in vivo. We found that cell type-specific deletion of PLCγ1 does not adversely affect the development and cellular morphology of midbrain dopamine neurons but does facilitate dopamine release from dopaminergic axon terminals in the striatum. The enhancement of dopamine release was accompanied by increased colocalization of vesicular monoamine transporter 2 (VMAT2) at dopaminergic axon terminals. Notably, dopamine neuron-specific knockout of PLCγ1 also led to heightened expression and colocalization of synapsin III, which controls the trafficking of synaptic vesicles. Furthermore, the knockdown of VMAT2 and synapsin III in dopamine neurons resulted in a significant attenuation of dopamine release, while this attenuation was less severe in PLCγ1 cKO mice. Our findings suggest that PLCγ1 in dopamine neurons could critically modulate dopamine release at axon terminals by directly or indirectly interacting with synaptic machinery, including VMAT2 and synapsin III. 2023-10-31T15:00:00Z https://scholarworks.unist.ac.kr/handle/201301/91666 Title: High-intensity irreversible electroporation targeting intracellular structures enhance tumor ablation in lung cancer models Author(s): Kim, Hong Bae; Youm, Jin Young; Yang, Joon-Mo; Sim, Sung Bo Abstract: This study aimed to optimize irreversible electroporation (IRE) parameters to enhance intracellular injury, specifically targeting nuclear and mitochondrial structures that are insufficiently affected by conventional protocols. To address limitations of standard 1000 similar to 2500 V/cm clinical settings, we experimentally and computationally evaluated both low- and high-electric-field conditions and identified pulse parameters capable of safely achieving electric field strengths exceeding 4,000 V/cm, values that remain below the predicted arcing threshold for our electrode configuration while permitting effective intracellular electroporation. In vitro studies using A549 lung cancer cells demonstrated that high-field IRE markedly intensified oxidative stress, resulting in a 30-fold increase in hydrogen peroxide production and pronounced disruption of mitochondrial membrane potential. Transmission electron microscopy further confirmed severe ultrastructural injury, including plasma membrane rupture, nuclear membrane deformation, and complete loss of mitochondrial cristae, culminating in irreversible cell death. In vivo experiments corroborated these findings: high-field IRE produced extensive and uniform tumor ablation, whereas conventional lower field strengths generated only localized and partial damage. These results indicate that elevating electric-field intensity in IRE protocols can overcome the inherent limitations of traditional approaches by reliably inducing intracellular organelle damage, suppressing cellular repair pathways, and enhancing overall ablation completeness. Further studies are warranted to evaluate long-term safety and therapeutic durability of high-field IRE in vivo. 2026-03-31T15:00:00Z https://scholarworks.unist.ac.kr/handle/201301/91656 Title: Orai1 acts as a novel Ca2+ signal switch, balancing erythropoiesis through KLF1 regulation Author(s): Lee, Yoon Young; Koh, Hyebin; Kim, Jieun; Kim, Sun-Uk; Lee, Jong-Hee; Park, Chan Young Abstract: Terminal erythropoiesis, the final stage of red blood cell maturation, is orchestrated by erythropoietin (EPO) and the master transcription factor, Kruppel-like factor 1 (KLF1). Recent studies highlight the importance of Ca2+ signaling in erythroid maturation; however, the underlying mechanisms remain elusive. Here we identify Orai1 as a novel EPO-responsive Ca2+ channel in erythroid cells, serving as a dynamic regulatory toggle that modulates KLF1 transcription and facilitates distinct phases of erythroid maturation. During the early stages, EPO-activated Orai1 suppresses KLF1 transcription through Ca2+-dependent NFAT2 activation and promoter binding, pausing erythroid maturation. As maturation progresses, Orai1 expression decreases, transitioning KLF1 regulation to an EPO-STAT5 pathway, thereby maintaining KLF1 expression and promoting terminal erythropoiesis. Using HUDEP-2 cells, umbilical cord blood and human pluripotent stem cell-derived CD71(+) erythroblasts, we observed a progressive downregulation of Orai1 and reduction in intracellular Ca2+ levels during terminal maturation. The functional inactivation of Orai1 via R91W mutants and CRISPR-Cas9 knockout enhanced KLF1 expression, leading to increased erythroid-specific gene expression, accelerated erythroid maturation, higher levels of globin production and improved enucleation efficiency. This study unveils the EPO-Orai1-Ca2+-NFAT2-KLF1 axis as a critical regulatory checkpoint in erythropoiesis and highlights Orai1 downregulation as a potential strategy to enhance clinical red blood cell production by promoting erythrocyte maturation. 2026-02-28T15:00:00Z