1. Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer.

    Journal of Hepatology 65(2):325 (2016) PMID 27117591

    Pediatric liver cancer is a rare but serious disease whose incidence is rising, and for which the therapeutic options are limited. Development of more targeted, less toxic therapies is hindered by the lack of an experimental animal model that captures the heterogeneity and metastatic capability ...
  2. Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks.

    Genome Research 25(2):257 (2015) PMID 25378249 PMCID PMC4315299

    We introduce a method for simultaneous prediction of microRNA-target interactions and their mediated competitive endogenous RNA (ceRNA) interactions. Using high-throughput validation assays in breast cancer cell lines, we show that our integrative approach significantly improves on microRNA-targ...
  3. Interrogation of a context-specific transcription factor network identifies novel regulators of pluripotency.

    Stem Cells 33(2):367 (2015) PMID 25336442 PMCID PMC4305010

    The predominant view of pluripotency regulation proposes a stable ground state with coordinated expression of key transcription factors (TFs) that prohibit differentiation. Another perspective suggests a more complexly regulated state involving competition between multiple lineage-specifying TFs...
  4. Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney.

    Nature Communications 6:8891 (2015) PMID 26573325 PMCID PMC4660214

    The X-linked BCL-6 co-repressor (BCOR) gene encodes a key constituent of a variant polycomb repressive complex (PRC) that is mutated or translocated in human cancers. Here we report on the identification of somatic internal tandem duplications (ITDs) clustering in the C terminus of BCOR in 23 of...
  5. Direct ChIP-Seq significance analysis improves target prediction.

    BMC Genomics 16 Suppl 5:S4 (2015) PMID 26040656 PMCID PMC4460594

    Chromatin immunoprecipitation followed by sequencing of protein-bound DNA fragments (ChIP-Seq) is an effective high-throughput methodology for the identification of context specific DNA fragments that are bound by specific proteins in vivo. Despite significant progress in the bioinformatics anal...
  6. Overexpression and constitutive nuclear localization of cohesin protease Separase protein correlates with high incidence of relapse and reduced overall survival in glioblastoma multiforme.

    Journal of Neuro-Oncology 119(1):27 (2014) PMID 24792645 PMCID PMC4160150

    Separase, an enzyme that cleaves the chromosomal cohesin during mitosis, is overexpressed in a wide range of human epithelial cancers of breast, bone and prostate (Meyer et al., Clin Cancer Res 15(8):2703-2710, 2009). Overexpression of Separase in animal models results in aneuploidy and tumorige...
  7. The miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland.

    Genes & Development 28(7):765 (2014) PMID 24636986 PMCID PMC4015488

    The mammary gland is a very dynamic organ that undergoes continuous remodeling. The critical regulators of this process are not fully understood. Here we identify the microRNA cluster miR-424(322)/503 as an important regulator of epithelial involution after pregnancy. Through the generation of a...
  8. A molecular signature predictive of indolent prostate cancer.

    Science Translational Medicine 5(202):202ra122 (2013) PMID 24027026 PMCID PMC3943244

    Many newly diagnosed prostate cancers present as low Gleason score tumors that require no treatment intervention. Distinguishing the many indolent tumors from the minority of lethal ones remains a major clinical challenge. We now show that low Gleason score prostate tumors can be distinguished a...
  9. tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma.

    PNAS 110(4):1404 (2013) PMID 23297232 PMCID PMC3557069

    Sequencing studies from several model systems have suggested that diverse and abundant small RNAs may be derived from tRNA, but the function of these molecules remains undefined. Here, we demonstrate that one such tRNA-derived fragment, cloned from human mature B cells and designated CU1276, in ...
  10. Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension.

    Circulation: Cardiovascular Genetics 5(3):336 (2012) PMID 22474227 PMCID PMC3380156

    Heritable and idiopathic pulmonary arterial hypertension (PAH) are phenotypically identical and associated with mutations in several genes related to transforming growth factor (TGF) beta signaling, including bone morphogenetic protein receptor type 2, activin receptor-like kinase 1, endoglin, a...
  11. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma.

    Cell 147(2):370 (2011) PMID 22000015 PMCID PMC3214599

    By analyzing gene expression data in glioblastoma in combination with matched microRNA profiles, we have uncovered a posttranscriptional regulation layer of surprising magnitude, comprising more than 248,000 microRNA (miR)-mediated interactions. These include ∼7,000 genes whose transcripts act a...
  12. A human B-cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centers.

    Molecular Systems Biology 6:377 (2010) PMID 20531406 PMCID PMC2913282

    Assembly of a transcriptional and post-translational molecular interaction network in B cells, the human B-cell interactome (HBCI), reveals a hierarchical, transcriptional control module, where MYB and FOXM1 act as synergistic master regulators of proliferation in the germinal center (GC). Eight...
  13. Integrated biochemical and computational approach identifies BCL6 direct target genes controlling multiple pathways in normal germinal center B cells.

    Blood 115(5):975 (2010) PMID 19965633 PMCID PMC2817639

    BCL6 is a transcriptional repressor required for mature B-cell germinal center (GC) formation and implicated in lymphomagenesis. BCL6's physiologic function is only partially known because the complete set of its targets in GC B cells has not been identified. To address this issue, we used an in...
  14. A systems biology approach to transcription factor binding site prediction.

    PLoS ONE 5(3):e9878 (2010) PMID 20360861 PMCID PMC2845628

    The elucidation of mammalian transcriptional regulatory networks holds great promise for both basic and translational research and remains one the greatest challenges to systems biology. Recent reverse engineering methods deduce regulatory interactions from large-scale mRNA expression profiles a...
  15. BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma.

    PNAS 106(27):11294 (2009) PMID 19549844 PMCID PMC2708681

    The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose deregulation by genomic lesions is implicated in the pathogenesis of GC-derived diffuse large B cell lymphoma (DLBCL) and, less frequently, follicular lymphoma (FL). The biol...
  16. Identification of the human mature B cell miRNome.

    Immunity 30(5):744 (2009) PMID 19446474 PMCID PMC2764486

    The full set of microRNAs (miRNAs) in the human genome is not known. Because presently known miRNAs have been identified by virtue of their abundant expression in a few cell types, many tissue-specific miRNAs remain unrevealed. To understand the role of miRNAs in B cell function and lymphomagene...
  17. ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes.

    PNAS 106(1):244 (2009) PMID 19118200 PMCID PMC2613038

    ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed at minimizing false-positive transcription factor targets. We prese...
  18. Correlating measurements across samples improves accuracy of large-scale expression profile experiments.

    Genome Biology 10(12):R143 (2009) PMID 20042104 PMCID PMC2812950

    Gene expression profiling technologies suffer from poor reproducibility across replicate experiments. However, when analyzing large datasets, probe-level expression profile correlation can help identify flawed probes and lead to the construction of truer probe sets with improved reproducibility....
  19. Tissue-specific regulatory elements in mammalian promoters.

    Molecular Systems Biology 3:73 (2007) PMID 17224917 PMCID PMC1800356

    Transcription factor-binding sites and the cis-regulatory modules they compose are central determinants of gene expression. We previously showed that binding site motifs and modules in proximal promoters can be used to predict a significant portion of mammalian tissue-specific transcription. Her...
  20. DNA motifs in human and mouse proximal promoters predict tissue-specific expression.

    PNAS 103(16):6275 (2006) PMID 16606849 PMCID PMC1458868

    Comprehensive identification of cis-regulatory elements is necessary for accurately reconstructing gene regulatory networks. We studied proximal promoters of human and mouse genes with differential expression across 56 terminally differentiated tissues. Using in silico techniques to discover, ev...