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. Reiter, R.J., Rosales-Corral, S.A., Tan, D.X., Acuna-Castroviejo, D., Qin, L., Yang, S.F., Xu, K. (2017). Melatonin, a full service anti-cancer agent: inhibition of initiation, progression and metastasis. Review. International Journal of Molecular Sciences, 18(4), 843. PMID: 28420185

  2. Yanming Wu, Zhao Zhang, Mauro Ezequiel Cenciarini,Cecilia Jazmín Proietti, Matias Amasino, Tao Hong, Mei Yang, Yiji Liao, Huai-Chin Chiang, Virginia Kaklamani, Rinath Jeselsohn, Ratna K. Vadlamudi, Tim Hui-Ming Huang, Rong Li, Carmine De Angelis, Xiaoyong Fu, Patricia V. Elizalde, Rachel Schiff, Myles Brown, Kexin Xu. Transcriptional Axis of EZH2-ERa-GREB1 Regulates Tamoxifen Resistance in Breast Cancer. Cancer Research, In press.

  3. Kexin Xu*, Christopher McNair*, Amy C. Mandigo, Matteo Benelli, Benjamin Leiby, Daniel Rodrigues, Johan Lindberg, Henrik Gronberg, Bram De Laere, Luc Dirix, Tapio Visakorpi, Fugen Li, Felix Y. Feng, Johann de Bono, Francesca Demichelis, Mark A Rubin, Myles Brown and Karen E. Knudsen. Differential impact of RB status on E2F1 reprogramming in human cancer. The Journal of Clinical Investigation, In press. (*, co-first authors)

  4. Kexin Xu*, Lixin Wan*, Yongkun Wei*, Jinfang Zhang*, Tao Han, Christopher Fry, Zhao Zhang, Yao Vickie Wang, Liyu Huang, Weiya Xia, Wei-Chao Chang, Wen-Chien Huang, Chien-Liang Liu, Yuan-Ching Chang, Yun Wu, Jinsong Liu, Victor X Jin, Jin Li, Xiangpeng Dai, Jianfeng Guo, Jia Liu, John M. Asara, Myles Brown, Mien-Chie Hung and Wenyi Wei. Phosphorylation of EZH2 by AMPK Suppresses PRC2 Methyltransferase Activity and Oncogenic Function. Molecular Cell, Accepted. (*, co-first authors)

  5. Xu, K., Kaneda, A. & Tsukada, Y. (2016). DNA and Histone Methylation in Particular Types of Cancer. Book Chapter D, SpringerLink, ISSN: 2196-9906.

  6. 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)

  7. 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)

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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