Department of Molecular Medicine
 

[ xu ] Kexin  XuPh.D.

Assistant Professor Tenure Track


Profile and Contact Information | Research | Laboratory


RESEARCH

 

Research Program

Epigenetic machinery plays an important role in the development, structure and functioning of organisms. Alterations in the epigenetic information lead to abnormal gene expression, and ultimately contribute to human diseases, such as cancer. Our research seeks to understand the fundamental roles of the epigenome in control of the context-specific transcriptional programs and how this control contributes to normal development or cancer progression. Specifically, we focus on the following topics:

(1). The interaction between tissue-specific transcription factors and epigenetic regulators in transcriptional control

(2). The crosstalk among distinct types of epigenetic modifications in shaping the physical structure of genome

(3). The response of epigenetic tags to the external and internal stimuli

(4). The development of new chemical probes targeting the master epigenetic enzymes in cancer pathogenesis

Our work is highly interdisciplinary and covers the fields of epigenomics, functional genomics, genome editing, biochemistry, bioinformatics and drug discovery. Findings from our studies will not only provide critical insights into the mechanisms of the epigenetic aberrations driving the pathogenesis of human cancers, but also lay solid foundations for the design of novel therapeutic targets or approaches.

 

Selected Publications

  1. Xu, K.*, Xu, H.*, He, H.H., Zang, C., Chen, CH., Chen, Y., Qin, Q., Wang, S., Wang, C., Hu, S., Li, F., Long, H., Brown, M. & Liu, X.S. (2015). Integrative analysis reveals the transcriptional collaboration between EZH2 and E2F1 in the regulation of cancer-related gene expression. Molecular Cancer Research. Accepted. (*: co-first authors)

  2. Xu, K. *, Wu, Z.J.*, Gorner, A.C., He, H.H., Cai, C., Lis, R.T., Wu, X., Stack, E.C., Loda, M., Liu, T., Xu, H., Cato, L., Thornton, J.E., Gregory, R.I., Morrissey, C., Vessella, R.L., Montironi, R., Magi-Galluzzi, C., Kantoff, P.W., Balk, S.P., Liu, X.S. & Brown, M. (2012). EZH2 oncogenic activity in castration resistant prostate cancer is Polycomb-independent. Science, 338(6113), 1465-9. (*: co-first authors)

  3. Linn, D.E., Yang, X., Xie, Y., Alfano, A., Deshmukh, D., Wang, X., Shimelis, H., Chen, H., Li, W., Xu, K., Chen, M. & Qiu, Y. (2012). Differential regulation of androgen receptor by PIM-1 kinases via phosphorylation-dependent recruitment of distinct ubiquitin E3 ligases. Journal of Biological Chemistry, 287(27), 22959-68. PMCID: PMC3391098

  4. Dai, B., Chen, H., Guo, S., Yang, X., Linn, D.E., Sun, F., Li, W., Guo, Z., Xu, K., Kim, O., Kong, X., Melamed, J., Qiu, S., Chen, H. & Qiu, Y. (2010). Compensatory upregulation of tyrosine kinase Etk/BMX in response to androgen deprivation promotes castration-resistant growth of prostate cancer cells. Cancer Research, 70(13), 5587-96.

  5. He, H.H., Meyer, C.A., Shin, H., Bailey, S.T., Wei, G., Wang, Q., Zhang, Y., Xu, K., Ni, M., Lupien, M., Mieczkowski, P., Lieb, J.D., Zhao, K., Brown, M. & Liu, X.S. (2010). Nucleosome dynamics define transcriptional enhancers. Nature Genetics, 42(4), 343-7. PMCID: PMC2932437

  6. Wang, Q., Li, W., Zhang, Y., Yuan, X., Xu, K., Yu, J., Chen, Z., Beroukhim, R., Wang, H., Lupien, M., Wu, T., Regan, M.M., Meyer, C.A., Carroll, J.S., Manrai, A.K., Jänne, O.A., Balk, S.P., Mehra, R., Han, B., Chinnaiyan, A.M., Rubin, M.A., True, L., Fiorentino, M., Fiore, C., Loda, M., Kantoff, P.W., Liu, X.S. & Brown, M. (2009). Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell, 138(2), 245-56. PMCID: PMC2726827

  7. Xu, K., Shimelis, H., Linn, D.E., Jiang, R., Yang, X., Sun, F., Guo, Z., Chen, H., Li, W., Chen, H., Kong, X., Melamed, J., Fang, S., Xiao, Z., Veenstra, T.D. & Qiu, Y. (2009). Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination. Cancer Cell, 15(4), 270-82. PMCID: PMC2848969

  8. Xie, Y., Xu, K., Linn, D.E., Yang, X., Guo, Z., Shimelis, H., Nakanishi, T., Ross, D.D., Chen, H., Fazli, L., Gleave, M.E. & Qiu, Y. (2008). The 44-kDa Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug-resistant activity in human prostate cancer cells. Journal of Biological Chemistry, 283(6), 3349-56.

  9. Guo, Z., Dai, B., Jiang, T., Xu, K., Xie, Y., Kim, O., Nesheiwat, I., Kong, X., Melamed, J., Handratta, V.D., Njar, V.C., Brodie, A. M., Yu, L.R., Veenstra, T.D., Chen, H. & Qiu, Y. (2006). Regulation of androgen receptor activity by tyrosine phosphorylation. Cancer Cell, 10(4), 309-19.

  10. Dai, B., Kim, O., Xie, Y., Guo, Z., Xu, K., Wang, B., Kong, X., Melamed, J., Chen, H., Bieberich, C.J., Borowsky, A.D., Kung, H. J., Wei, G., Ostrowski, M.C., Brodie, A.M. & Qiu, Y. (2006). Tyrosine kinase Etk/BMX is up-regulated in human prostate cancer and its overexpression induces prostate intraepithelial neoplasia in mouse. Cancer Research, 66(16), 8058-64.

  11. Xie, Y., Xu, K., Dai, B., Guo, Z., Jiang, T., Chen, H. & Qiu, Y. (2006). The 44 kDa Pim-1 kinase directly interacts with tyrosine kinase Etk/BMX and protects human prostate cancer cells from apoptosis induced by chemotherapeutic drugs. Oncogene, 25(1), 70-8