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Tyekucheva, Svitlana

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Tyekucheva

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Svitlana

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Tyekucheva, Svitlana
Author's Publications: search.filters.isAuthorOfPublication.7b0a054d-45d5-4645-b68a-e309d9fbc1b3

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Now showing 1 - 5 of 5
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    Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer
    (Nature Publishing Group UK, 2017) Tyekucheva, Svitlana; Bowden, Michaela; Bango, Clyde; Giunchi, Francesca; Huang, Ying; Zhou, Chensheng; Bondi, Arrigo; Lis, Rosina; Van Hemelrijck, Mieke; Andrén, Ove; Andersson, Sven-Olof; Watson, R. William; Pennington, Stephen; Finn, Stephen P.; Martin, Neil; Stampfer, Meir; Parmigiani, Giovanni; Penney, Kathryn; Fiorentino, Michelangelo; Mucci, Lorelei; Loda, Massimo
    While progression from normal prostatic epithelium to invasive cancer is driven by molecular alterations, tumor cells and cells in the cancer microenvironment are co-dependent and co-evolve. Few human studies to date have focused on stroma. Here, we performed gene expression profiling of laser capture microdissected normal non-neoplastic prostate epithelial tissue and compared it to non-transformed and neoplastic low-grade and high-grade prostate epithelial tissue from radical prostatectomies, each with its immediately surrounding stroma. Whereas benign epithelium in prostates with and without tumor were similar in gene expression space, stroma away from tumor was significantly different from that in prostates without cancer. A stromal gene signature reflecting bone remodeling and immune-related pathways was upregulated in high compared to low-Gleason grade cases. In validation data, the signature discriminated cases that developed metastasis from those that did not. These data suggest that the microenvironment may influence prostate cancer initiation, maintenance, and metastatic progression.
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    A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis
    (Backwell Publishing Ltd, 2014) Zadra, Giorgia; Photopoulos, Cornelia; Tyekucheva, Svitlana; Heidari, Pedram; Weng, Qing Ping; Fedele, Giuseppe; Liu, Hong; Scaglia, Natalia; Priolo, Carmen; Sicinska, Ewa; Mahmood, Umar; Signoretti, Sabina; Birnberg, Neal; Loda, Massimo
    5′AMP-activated kinase (AMPK) constitutes a hub for cellular metabolic and growth control, thus representing an ideal therapeutic target for prostate cancers (PCas) characterized by increased lipogenesis and activation of mTORC1 pathway. However, whether AMPK activation itself is sufficient to block cancer cell growth remains to be determined. A small molecule screening was performed and identified MT 63–78, a specific and potent direct AMPK activator. Here, we show that direct activation of AMPK inhibits PCa cell growth in androgen sensitive and castration resistant PCa (CRPC) models, induces mitotic arrest, and apoptosis. In vivo, AMPK activation is sufficient to reduce PCa growth, whereas the allelic loss of its catalytic subunits fosters PCa development. Importantly, despite mTORC1 blockade, the suppression of de novo lipogenesis is the underpinning mechanism responsible for AMPK-mediated PCa growth inhibition, suggesting AMPK as a therapeutic target especially for lipogenesis-driven PCas. Finally, we demonstrate that MT 63–78 enhances the growth inhibitory effect of AR signaling inhibitors MDV3100 and abiraterone. This study thus provides a rationale for their combined use in CRPC treatment.
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    A Network of Epigenetic Regulators Guide Developmental Hematopoiesis In Vivo
    (2013) Huang, Hsuan-Ting; Kathrein, Katie L.; Barton, Abby; Gitlin, Zachary; Huang, Yue-Hua; Ward, Thomas P.; Hofmann, Oliver; Dibiase, Anthony; Song, Anhua; Tyekucheva, Svitlana; Hide, Winston; Zhou, Yi; Zon, Leonard
    The initiation of cellular programs is orchestrated by key transcription factors and chromatin regulators that activate or inhibit target gene expression. To generate a compendium of chromatin factors that establish the epigenetic code during developmental hematopoiesis, a large-scale reverse genetic screen was conducted targeting orthologs of 425 human chromatin factors in zebrafish. A set of chromatin regulators was identified that target different stages of primitive and definitive blood formation, including factors not previously implicated in hematopoiesis. We identified 15 factors that regulate development of primitive erythroid progenitors and 29 factors that regulate development of definitive stem and progenitor cells. These chromatin factors are associated with SWI/SNF and ISWI chromatin remodeling, SET1 methyltransferase, CBP/P300/HBO1/NuA4 acetyltransferase, HDAC/NuRD deacetylase, and Polycomb repressive complexes. Our work provides a comprehensive view of how specific chromatin factors and their associated complexes play a major role in the establishment of hematopoietic cells in vivo.
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    Integrating Diverse Genomic Data Using Gene Sets
    (BioMed Central, 2011) Tyekucheva, Svitlana; Marchionni, Luigi; Karchin, Rachel; Parmigiani, Giovanni
    We introduce and evaluate data analysis methods to interpret simultaneous measurement of multiple genomic features made on the same biological samples. Our tools use gene sets to provide an interpretable common scale for diverse genomic information. We show we can detect genetic effects, although they may act through different mechanisms in different samples, and show we can discover and validate important disease-related gene sets that would not be discovered by analyzing each data type individually.
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    curatedOvarianData: clinically annotated data for the ovarian cancer transcriptome
    (Oxford University Press, 2013) Ganzfried, Benjamin Frederick; Riester, Markus; Haibe-Kains, Benjamin; Risch, Thomas; Tyekucheva, Svitlana; Jazic, Ina; Wang, Xin; Ahmadifar, Mahnaz; Birrer, Michael J.; Parmigiani, Giovanni; Huttenhower, Curtis; Waldron, Levi
    This article introduces a manually curated data collection for gene expression meta-analysis of patients with ovarian cancer and software for reproducible preparation of similar databases. This resource provides uniformly prepared microarray data for 2970 patients from 23 studies with curated and documented clinical metadata. It allows users to efficiently identify studies and patient subgroups of interest for analysis and to perform meta-analysis immediately without the challenges posed by harmonizing heterogeneous microarray technologies, study designs, expression data processing methods and clinical data formats. We confirm that the recently proposed biomarker CXCL12 is associated with patient survival, independently of stage and optimal surgical debulking, which was possible only through meta-analysis owing to insufficient sample sizes of the individual studies. The database is implemented as the curatedOvarianData Bioconductor package for the R statistical computing language, providing a comprehensive and flexible resource for clinically oriented investigation of the ovarian cancer transcriptome. The package and pipeline for producing it are available from http://bcb.dfci.harvard.edu/ovariancancer. Database URL: http://bcb.dfci.harvard.edu/ovariancancer