Our long-term goal is to understand the regulatory mechanisms of how the transcriptional machinery is fine-tuned by signaling pathways and environmental perturbations in different developmental, physiological, and pathological contexts.
First, transcription cofactor Mediator complex is dysregulated in a variety of human cancers and other diseases. Using Drosophila and cultured cancer cells as model systems, we study the function and regulation of CDK8, a subunit of the Mediator complex, by identifying their upstream regulators and downstream effectors. We found that CDK8 inhibits lipogenesis in Drosophila, mammalian cells and mouse, and that CDK8 plays a tumor-suppressive function in endometrial cancer cells. We also study other subunits of the Mediator complexes. Second, we study the mechanisms of how Wnt signaling regulates lipid homeostasis. Deregulated Wnt signaling and altered lipid metabolism have been linked to obesity, diabetes, and various cancers. We found that hyperactivated Wnt signaling disrupts fat metabolism in Drosophila larvae, and that peptide boronic acids can potently rescue the fat defects by inhibiting Wg signaling through stabilization of α-catenin. Currently, we are studying the molecular mechanisms of how active Wnt signaling reduces lipogenesis and stimulate lipolysis. Third, we also investigate the epigenetic regulation of gene expression during Drosophila development, as well as mechanisms that control cellular growth and cell proliferation in Drosophila and mammalian cells.
ORCID identifier: https://orcid.org/0000-0002-4483-4336
SelectedPublications:
2. Li, X.,Zhang, M., Liu, M., Liu, T.-H., Hemba-Waduge, R., Ji,J.Y. (2022) CDK8 attenuates lipogenesis by inhibiting SREBP-dependenttranscription in Drosophila. Disease Models & Mechanisms 15 (11), DOI: 10.1242/dmm.049650
3. Li, X., Liu, M., Ren, X., Loncle, N., Wang, Q., Hemba-Waduge, R., Boube,M., Bourbon, H.-M. G., Ni, J.Q., and Ji, J.Y. (2020) The Mediator CDK-Cyclin Ccomplex modulates Dpp signaling in Drosophila by stimulatingMad-dependent transcription. PLoS Genetics 16(5): e1008832.
4. Li, X., Liu, M., and Ji, J.Y.(2019) Understanding obesity as a risk factor for uterine tumors using Drosophila.Adv. Exp. Med. Biol. 1167, 129-155. doi: 10.1007/978-3-030-23629-8_8.
5. Zhang, T., Hsu, F.N., Xie, X.J., Li, X.,Liu, M., Gao, X., Pei, X., Liao, Y., Du, W., and Ji, J.Y. (2017) Reversal of hyperactive Wnt signaling-dependent adipocytedefects by peptide boronic acids. Proc. Natl. Acad. Sci. USA, 114 (36):E7469-E7478.
6. Xie, X.J., Hsu, F.N., Gao, X., Xu,W., Ni, J.Q., Xing, Y., Huang, L., Hsiao, H.C., Zheng, H., Wang, C., Zheng, Y.,Xiaoli, A.M., Yang, F., Bondos, S.E., Ji,J.Y. (2015) CDK8-Cyclin Cmediates nutritional regulation of developmental transitions through theEcdysone Receptor in Drosophila. PLoS Biology 13(7), e1002207.
“Topics” (Keywords/Tags): Wnt signaling, transcription, lipid homeostasis, cell growth and proliferation.
Link to lab website:
https://medicine.tulane.edu/departments/biochemistry-molecular-biology/faculty/jun-yuan-ji-phd
https://medicine.tulane.edu/ji-laboratory
