Our laboratory focuses on understanding the genetic and epigenetic pathways to prostate cancer. A number of key transcription factors, including the Androgen Receptor, the Polycomb group protein EZH2, and the TMPRSS2:ERG gene fusions, have been related to epigenetic changes and implicated in prostate cancer. However, their downstream pathways remain largely unknown. Using “-omics” approaches we have identified a number of target genes and molecular pathways of these transcription factors. Our study will elucidate the specific pathways of these transcription factors and how they may crosstalk with each other to form an intertwined network. Findings from our study will then be applied to understand the hormone-refractory prostate tumors and help the design of novel therapeutic targets.
As transcriptional regulation, for instance those by EZH2, eventually leads to inheritable epigenetic changes and thus altered chromatin status. Epigenetic mechanisms may be fundamental to tumorigenesis. Based on our previous work, we hypothesized that in aggressive tumors altered transcriptional controls and chromatin states lead to de-differentiation and a stem cell like cellular status. In our study we will reveal the link between transcriptional control and epigenetic changes including histone methylation, DNA methylation and the regulation of miRNAs.
Selected Publications:
Yu J, Cao Q, Mehra R, Laxman B, Yu J, Tomlins SA, Creighton CJ, Dhanasekaran SM, Shen R, Chen G, Morris DS, Marquez VE, Shah RB, Ghosh D, Varambally S, Chinnaiyan AM. Integrative genomics analysis reveals silencing of β-adrenergic signaling by polycomb in prostate cancer. Cancer Cell. 2007; 12 (5). Featured Article.
Yu J, Yu JJ, Rhodes DR, Tomlins SA, Cao X, Chen G, Mehra R, Wang X, Ghosh D, Shah RB, Varambally S, Pienta KJ, Chinnaiyan AM. A polycomb repression signature in metastatic prostate cancer predicts cancer outcome. Cancer Res. 2007; 67(22): 10657-63. Featured Article.
Yu JJ*, Yu J*, Cordero KE, Johnson MD, Ghosh D, Rae JM, Lippman ME, Chinnaiyan AM. A transcriptional fingerprint of estrogen in human breast cancer predicts patient survival. Neoplasia. 2008 Jan;10(1):79-88. *Co-authors with equal contribution
Wang Q, Li W, Zhang Y, Yuan X, Xu K, Yu J, Chen Z, Beoukhim R, Wang H, Lupien M, Wu T, Regan MM, Meyer CA, Carroll JS, Manrai AK, Janne OA, Balk SP, Mehra R, Han B, Chinnaiyan AM, Rubin MA, True L, Fiorentino M, Fiore C, Loda M, Kantoff PW, Liu XS, Brown M. Reprogrammed androgen receptor function in androgen-independent prostate cancer. Cell. 2009 Jul 23;138(2):245-56.
Maher CA, Palanisamy N, Brenner JC, Cao, X, Kalyana-Sundaram S, Lou S, Khrebtukova I, Barrette T, Grasso C, Yu J, Lonigro R, Schroth G, Kumar-Sinha C, Chinnaiyan AM. Chimeric transcript discovery by paired-end transcriptome sequencing. Proc Natl Acad Sci U S A. 2009 Jul 10.
