- B.S., Cell Biology, Lanzhou University, 1994
- M.S., Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Adademy of Sciences, 1997
- Ph.D., Zoology, University of Washington, 2003
- Post-doc., Massachusetts General Hospital Cancer Center and Harvard Medical School (Nicholas Dyson)
Dr. Ji's laboratory is interested in cell cycle and transcriptional regulation during development and tumorigenesis. Using Drosophila and cultured human cancer cell lines as model systems, we combine genetic, cell biological, and biochemical approaches to elucidate the molecular and genetic regulatory circuits that control cell proliferation. Specifically, our major focus is to study the functions and regulation of Cyclin-dependent kinase 8 (CDK8). By performing genetic screens using Drosophila, we identified CDK8 as a potent inhibitor of E2F1, which is a key transcription factor that regulates the G1 to S-phase transition. In both Drosophila and human cancer cells, we observed that CDK8 inhibits E2F1-dependent transcription by directly binding to and phosphorylating E2F1, which may turn off the re-initiation of E2F1-mediated transcription. Interestingly, CDK8 is recently identified as an oncoprotein. The genes encoding CDK8 and its regulatory partner Cyclin C (CCNC) are frequently amplified or mutated in various types of human cancers. Importantly, inhibiting CDK8 potently blocks the growth of colorectal cancer cells that harbor CDK8 amplification, suggesting that CDK8 kinase is a promising drug target. Therefore, it is important to understand the regulatory network, including both upstream regulators and downstream effectors, of CDK8-Cyclin C in both normal development and tumorigenesis.
Zheng, Y., Hsu, F.N., Xu, W., Xie, X.J., Ren, X., Gao, X., Ni, J.Q., and Ji, J.Y.# (2014) A developmental genetic analysis of the lysine demethylase KDM2 in Drosophila melanogaster. Mechanisms of Development, in press. (# Corresponding author)
Xu, W.#, Amire-Brahimi, B., Xie, X.J., Huang, L., Ji, J.Y.# (2014) All-atomic Molecular Dynamic Studies of Human CDK8: Insight on A-loop, Point Mutations and Binding with Its Partner CycC. Computational Biology and Chemistry 51, 1-14. (# Corresponding authors)
Zhang, T., Liao, Y., Hsu, F.N., Zhang, R., Searle, J.S., Pei, X., Li, X., Ryoo, H.D., Ji, J.Y., Du, W. (2014) Elevated TORC1 activity mediates synthetic lethal interaction between deregulated Wnt signaling and Rb inactivation. PLoS Genetics 10, e1004357.
Wang, C., Ji, J.Y., Tian, L., and Pestell, R.G. (2014) Transcriptional regulation of lipogenesis as a therapeutic target for cancer treatment. R. Kumar (ed.) Nuclear Signaling Pathways and Targeting Transcription in Cancer, Cancer Drug Discovery and Development, pp 259-275. DOI 10.1007/978-1-4614-8039-6_10; Springer New York
Ren, X., Sun, J., Housden, B.E., Hu, Y., Roesel, C., Lin, S., Liu, L.P., Yang, Z., Mao, D., Sun, L., Wu, Q., Ji, J.Y., Xi, J., Mohr, S.E., Xu, J., Perrimon, N., Ni, J.Q. (2013) Optimized gene editing technology for Drosophila melanogaster using germ line-specific Cas9. Proc. Natl. Acad. Sci. USA 110, 19012-19017.
Gu, W., Wang, C., Li, W., Zhou, J., Yuan, C., Xie, X.J., Addya, S., Kong, B.# and Ji, J.Y.# (2013) Tumor suppressive effects of CDK8 in endometrial cancer cells. Cell Cycle 12, 987-999. (# Corresponding authors)
Ji, J.Y.*, Miles, W.O. Korenjak, M., Zheng, Y., and Dyson, N.J. (2012) In vivo regulation of E2F1 by Polycomb group genes in Drosophila. G3: Genes, Genomes, Genetics, 2, 1651-1660. (* Corresponding author)
Herr, A., Longworth, M. Ji, J.Y., Korenjak, M., Macalpine, D.M., and Dyson, N.J. (2012) Identification of E2F target genes that are rate limiting for dE2F1-dependent cell proliferation. Developmental Dynamics 241, 1695-1707.
Li, W., Tai, Y., Zhou, J., Gu, W., Bai, Z., Zhou, T., Zhong, Z., McCue, P.A., Sang, N., Ji, J.Y., Kong, B., Jiang, J., and Wang, C. (2012) Repression of endometrial tumor growth by targeting SREBP1 and lipogenesis. Cell Cycle 11, 2348-2358.
Zhao, X.*, Feng, D.*, Wang, Q.*, Abdulla, A., Xie, X.J., Zhou, J., Sun, Y., Yang, E.S., Liu, L.P., Vaitheesvaran, B., Bridges, L., Kurland, I., Strich, R., Ni, J.Q., Wang, C., Ericsson, J., Pessin, J.E., Ji, J.Y.#, and Yang, F.# (2012) Regulation of lipogenesis by cyclin-dependent kinase 8–mediated control of SREBP-1. Journal of Clinical Investigation 122, 2417-2427. (* Equal contributors; # Corresponding authors)
Miles, W.O., Tschop, K., Herr, A., Ji, J.Y., and Dyson, N.J. (2012) Pumilio facilitates miRNA regulation of the E2F3 oncogene. Genes & Development 26, 356-368.
Xu, W., and Ji, J.Y. (2011) Dysregulation of CDK8 and Cyclin C in tumorigenesis. Journal of Genetics and Genomics 38, 439-452.
Mulligan, P., Yang, F., Di Stefano, L., Ji, J.Y., Ouyang, J., Nishikawa, J.L., Toiber, D., Kulkarni, M., Wang, Q., Najafi-Shoushtari, S.H., Mostoslavsky, R., Gygi, S.P., Gill, G., Dyson, N.J., and Näär, A.M. (2011) A SIRT1-LSD1 corepressor complex regulates Notch target gene expression and development. Molecular Cell 42, 689-699.
Walker, A.K., Yang, F., Jiang, K., Ji, J.Y., Watts, J.L., Purushotham, A., Boss, O., Hirsch, M.L., Ribich, S., Smith, J.J., Israelian, K., Westphal, C.H., Rodgers, J.T., Shioda, T., Elson, S. L., Mulligan, P., Najafi-Shoushtari, H., Black, J. C., Thakur, J.K., Kadyk, L.C., Whetstine, J.R., Mostoslavsky, R., Puigserver, P., Li, X., Dyson, N.J., Hart, A.C., and Naar, A. M. (2010) Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes & Development 24, 1403-1417.
Ji, J.Y. and Dyson, N.J. (2010) Interplay between Cyclin-dependent Kinases and E2F-dependent Transcription. In Cell Cycle Deregulation in Cancer (ed. G. Enders), Springer Science , pp 23-41.
Zhang, J., Ji, J.Y., Yu, M., Overholtzer, M., Smolen, G.A., Wang, R., Brugge, J.S., Dyson, N.J., and Haber, D.A. 2009. YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway. Nat Cell Biol 11: 1444-1450.
Morris, E.J.*, Ji, J.Y.*, Yang, F., Di Stefano, L., Herr, A., Moon, N.S., Kwon, E.J., Haigis, K.M., Naar, A.M., and Dyson, N.J. 2008. E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8. Nature 455: 552-556. (* Equal contributors)
Di Stefano, L., Ji, J.Y., Moon, N.S., Herr, A., and Dyson, N. 2007. Mutation of Drosophila Lsd1 disrupts H3-K4 methylation, resulting in tissue-specific defects during development. Curr Biol 17: 808-812.
Morris, E.J., Michaud, W.A., Ji, J.Y., Moon, N.S., Rocco, J.W., and Dyson, N.J. 2006. Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo. PLoS Genet 2: e196.
Ji, J.Y., Crest, J., and Schubiger, G. 2005. Genetic interactions between Cdk1-CyclinB and the Separase complex in Drosophila. Development 132: 1875-1884.
Ji, J.Y., Squirrell, J.M., and Schubiger, G. 2004. Both cyclin B levels and DNA-replication checkpoint control the early embryonic mitoses in Drosophila. Development 131: 401-411.
Ji, J.Y., Haghnia, M., Trusty, C., Goldstein, L.S., and Schubiger, G. 2002. A genetic screen for suppressors and enhancers of the Drosophila cdk1-cyclin B identifies maternal factors that regulate microtubule and microfilament stability. Genetics 162: 1179-1195.
- Molecular, Cellular and Developmental Genetics:
Transcriptional regulation of lipid metabolism and tumorigenesis