Discover Ras effectors
Chang, E. C., Barr, M., Wang, Y., Jung, V., Xu, H. P., and Wigler, M. 1994. Cooperative interaction of S. pombe proteins required for mating and morphogenesis. Cell, 79: 131-141. PMID 7923372
Zheng, Z., Cheng, C-M, Fu, X-R, Chen, L-Y, Xu, L., Terrillon, S., Wong, S. T., Bar-Sagi, D., Zhou, S., and Chang, E. C., 2012. CHMP6 and VPS4A mediate recycling of Ras to the plasma membrane to promote growth factor signaling. Oncogene. 31:4630-4638. PMID: 22231449.
Ras regulation—coordinating multiple Ras pathways by the same Ras protein
Onken, B., Wiener, H., Philips, M. R., and Chang, E. C. 2006. Compartmentalized signaling of Ras in fission yeast. Proc. Natl. Acad. Sci. USA., 103(24): 9045-9050. PMID: 16754851; PMC1482563.
Cheng, CM, Li, H, Gasman, S, Huang, J, Schiff, R, Chang, E. C. 2011. Compartmentalized Ras proteins transform NIH3T3 cells with different efficiencies. Mol. Cell. Biol. 31:983-997. PMC3067814.
Young E, Zheng ZY, Wilkins AD, Jeong HT, Li M, Lichtarge O, Chang EC. 2014, Regulation of ras localization and cell transformation by evolutionarily conserved palmitoyltransferases. Mol Cell Biol 34:374-85. PMID: 24248599.
Papadaki, P., Pizon, V., Onken, B., and Chang, E. C. 2002. Two Ras pathways in fission yeast are differentially regulated by two Ras guanine nucleotide exchange factors. Mol. Cell. Biol., 22(13): 4598-4606. PMID: 12052869; PMC133927
Discover a new Ras pathway in breast cancer and develop a drug screening strategy to target Ras for therapy
Zheng, Z.-y, Tian, L., Cheng, F., Bu, W., Liao, Y-h., Li, Y., Lewis, M. T., Edwards, D., Zwaka, T. P., Hilsenbeck, S. G., Medina, D., Perou, C. M., Ceighton, C. J., Zhang, X., Chang, E. C., 2015. Wild type N-Ras, overexpressed in basal-like breast cancer, promotes tumor formation by inducing IL8 secretion via JAK2 activation. Cell Rep. 12: 511-524. PMCID: PMC4512851.
Zheng, Z.-y., Li, J., Li, F., Zhu, Y., Cui, K., Wong, S.T., Chang, E.C*., and Liao, Y.-h.* (2018). Induction of N-Ras degradation by flunarizine-mediated autophagy. Scientific Reports, 8, 16932. PMCID: PMC6240051 (*Shared senior authorship)
Zheng ZY, Elsarraj H, Lei JT, Hong Y, Anurag M, Feng L, Kennedy H, Shen Y, Lo F, Zhao Z, Zhang B, Zhang XH, Tawfik OW, Behbod F*, Chang EC*. Elevated NRAS expression during DCIS is a potential driver for progression to basal-like properties and local invasiveness. Breast Cancer Res. 2022;24(1):68. PMID: 36258226; PMCID: PMC9578182. (*Shared senior authorship)
Define the molecular activities of a potential breast cancer suppressor, Int6
Yen, H.-c.S., and Chang, E.C. (2000). Yin6, a fission yeast Int6 homolog, complexes with Moe1 and plays a role in chromosome segregation. Proc Natl Acad Sci USA 97, 14370-14375. PMCID: PMC18925
Yen, H-C., Gordon, C., and Chang, E. C. 2003. Schizosaccharomyces pombe Int6 and Ras homologs regulate cell division and mitotic fidelity via the proteasome. Cell, 112(2): 207-217. PMID: 12553909
Sha, Z., Brill, L. M., Cabrera, R., Kleifeld, O., Glickman, M. H., Wolf, D. A., and Chang, E. C*. 2009. eIF3 interactome reveals the translasome, a supercomplex linking protein synthesis and degradation machineries. Mol Cell. 36 141-152. (*shared corresponding authorship with Wolf). PMCID: PMC2789680.
Suo, J., Sneider, S., Mills, G., Creighton, C. J., Schiff, R., Lloyd, R, and Chang, E. C. 2011. Int6 regulates both proteasomal degradation and translation initiation and is critical for proper formation of acini by human mammary epithelium. Oncogene 30: 724-736. PMID: 20890303 PMCID: PMC3017639.
Discover drivers for endocrine therapy resistance and metastasis in breast cancer
Griffith OL, Spies NC, Anurag M, Griffith M, Luo J, Tu D, Yeo B, Kunisaki J, Miller CA, Krysiak K, Hundal J, Ainscough BJ, Skidmore ZL, Campbell K, Kumar R, Fronick C, Cook L, Snider JE, Davies S, Kavuri SM, Chang, EC, Magrini V, Larson DE, Fulton RS, Liu S, Leung S, Voduc D, Bose R, Dowsett M, Wilson RK, Nielsen TO, Mardis ER, Ellis MJ (2018). The prognostic effects of somatic mutations in ER-positive breast cancer. Nat Commun 9:3476. PMCID: PMC6123466.
Zheng, Z., Anurag, M., Jin Cao, J., Lei, J. T., Du, X-h. Li, J., Lavere, P., Singh, P., Seker, S. Wei Song, Peng, J.-h, Kim, B.-j, Nguyen, T., Cakar, B., Chan, D., Chen, X., Banks K. C., Lanman, R. B., Nemati M. S., Zhang, X., Vasakair, S., Zhang, B., Susan Hilsenbeck, S., Foulds, C. E., Ellis, M. J.*, Chang, E. C.*. (2020) Neurofibromin is an estrogen receptor -a transcriptional corepressor in breast cancer. Cancer Cell, 16: 387-402. (*shared corresponding authorship with Ellis). PMID: 32142667, PMCID:7286719