Browsing by Author "Wang, Xiaobei"
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Item Open Access Inhibition of Sphingosine Kinase 2 Results in PARK2-Mediated Mitophagy and Induces Apoptosis in Multiple Myeloma.(Current oncology (Toronto, Ont.), 2023-03) Wu, Jian; Fan, Shengjun; Feinberg, Daniel; Wang, Xiaobei; Jabbar, Shaima; Kang, YubinMitophagy plays an important role in maintaining mitochondrial homeostasis by clearing damaged mitochondria. Sphingosine kinase 2 (SK2), a type of sphingosine kinase, is an important metabolic enzyme involved in generating sphingosine-1-phosphate. Its expression level is elevated in many cancers and is associated with poor clinical outcomes. However, the relationship between SK2 and mitochondrial dysfunction remains unclear. We found that the genetic downregulation of SK2 or treatment with ABC294640, a specific inhibitor of SK2, induced mitophagy and apoptosis in multiple myeloma cell lines. We showed that mitophagy correlates with apoptosis induction and likely occurs through the SET/PP2AC/PARK2 pathway, where inhibiting PP2AC activity may rescue this process. Furthermore, we found that PP2AC and PARK2 form a complex, suggesting that they might regulate mitophagy through protein-protein interactions. Our study demonstrates the important role of SK2 in regulating mitophagy and provides new insights into the mechanism of mitophagy in multiple myeloma.Item Open Access Longitudinal intravital imaging of mouse placenta.(Science advances, 2024-03) Zhu, Xiaoyi; Huang, Qiang; Jiang, Laiming; Nguyen, Van-Tu; Vu, Tri; Devlin, Garth; Shaima, Jabbar; Wang, Xiaobei; Chen, Yong; Ma, Lijun; Xiang, Kun; Wang, Ergang; Rong, Qiangzhou; Zhou, Qifa; Kang, Yubin; Asokan, Aravind; Feng, Liping; Hsu, Shiao-Wen D; Shen, Xiling; Yao, JunjieStudying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enables high-resolution photoacoustic and fluorescence imaging of placental development throughout the pregnancy. The placenta window exhibits excellent transparency for light and sound. By combining the placenta window with ultrafast functional photoacoustic microscopy, we were able to investigate the placental development during the entire mouse pregnancy, providing unprecedented spatiotemporal details. Consequently, we examined the acute responses of the placenta to alcohol consumption and cardiac arrest, as well as chronic abnormalities in an inflammation model. We have also observed viral gene delivery at the single-cell level and chemical diffusion through the placenta by using fluorescence imaging. Our results demonstrate that intravital imaging through the placenta window can be a powerful tool for studying placenta functions and understanding the placental origins of adverse pregnancy outcomes.