The goal of the Miles lab is to understand how the post-transcriptional regulatory network modulates the transcriptome and controls changes in the proteome in human cancer cells. In particular, we focus on understanding how RNA-binding proteins (RBPs) and miRNAs modulate the translation potential of mRNAs. Our work currently centers of the PUMILIO family of RBPs and determining how these factors cooperate with miRNAs to regulate the translation of new synthesized mRNAs and on elucidating the role of these proteins in sustaining cancer cell proliferation and survival. We are particularly interested in understanding how RBPs function to regulate the transcriptional de-regulation associated with loss of the Retinoblastoma 1 (pRB) tumor-suppressor gene. We use RBP-RNA capture protocols, RNA-seq and Quantitative Mass Spectrometry to measure the transcriptional, post-transcriptional and proteomic changes in normal human cells, cancer cells and primary patient samples. 

 

Miles WO*, Lembo A, Volorio A, Brachtel E, Tian B, Sgroi D, Provero P and Dyson NJ. Alternative polyadenylation in triple-negative breast tumors allows NRAS and c-JUN to bypass PUMILIO post-transcriptional regulation. Cancer Research, Oct 10 2016, PMID: 27758885 * Co-corresponding Author

 

Miles WO, Bourdeaux J, Lepesant J, Texier M, Kerenyi MA, Nakakido M, Hamamoto R, Orkin SH, Dyson NJ and Di Stefano L. Identification of a feedback regulatory loop between dLsd1 and LSD2 and the Pumilio post-transcriptional repressor complex. Molecular Cell Biology, November 2015, 36(20). PMID26438601

 

Nicolay BN, Danielian PS, Kottakis F, Lapek JD Jr, Sanidas I, Miles WO, Dehnad M, Tschöp K, Gierut JJ, Manning AL, Morris R, Haigis K, Bardeesy N, Lees JA, Haas W, Dyson NJ. Proteomic analysis of pRb loss highlights a signature of decreased mitochondrial oxidative phosphorylation. Genes and Development 2015 Aug 27, PMID: 26314710

 

Miles WO and Dyson NJ. RB-loss puts focus on Myc. Nature Cell Biology, 2015, Jul 31; 17 (8):968-9. PMID26239529

 

Miles WO, Korenjak M, Dyer M, Provero P and Dyson NJ. Post-transcriptional regulation by NANOS counterbalances E2F activity to suppress apoptotic responses in pRb deficient cells. EMBO Journal, October 2014, 33(19):2201-15. PMC4282507

 

Miles WO, Tschöp K, Herr A, Ji JY, Dyson, NJ. Pumilio facilitates miRNA regulation of the E2F3 oncogene. Genes and Development, 2012 26(4): p356-368. PMC3289884

 

Ji, JY, Miles WO, Korenjak M, Zheng Y and Dyson NJ. In Vivo Regulation of E2F1 by Polycomb Group Genes in Drosophila. Genes, Genomes and Genetics, Dec 2012. 2: p1651-1660. PMC3516486

 

Miles WO, Jaffray E, Campbell SG, Takeda S, Bayston LJ, Basu SP, Li M, Raftery LA, Ashe MP, Hay RT, Ashe HL. Medea SUMOylation restricts the signaling range of the Dpp morphogen in the Drosophila embryo. Genes and Development, Sep 2008 15; 22(18):2578-90. PMC2546696

 

 

Groups:

1. Center for RNA Biology
2. Solid tumor Biology at The Ohio State University Comprehensive Cancer Center and James Cancer Hospital