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Wang, Yang

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Wang

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Wang, Yang
Author's Publications: search.filters.isAuthorOfPublication.4db8c462-58e8-4222-a742-07f67c001242

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    An inter‐species protein–protein interaction network across vast evolutionary distance
    (John Wiley and Sons Inc., 2016) Zhong, Quan; Pevzner, Samuel J; Hao, Tong; Wang, Yang; Mosca, Roberto; Menche, Jörg; Taipale, Mikko; Taşan, Murat; Fan, Changyu; Yang, Xinping; Haley, Patrick; Murray, Ryan R; Mer, Flora; Gebreab, Fana; Tam, Stanley; MacWilliams, Andrew; Dricot, Amélie; Reichert, Patrick; Santhanam, Balaji; Ghamsari, Lila; Calderwood, Michael; Rolland, Thomas; Charloteaux, Benoit; Lindquist, Susan; Barabási, Albert‐László; Hill, David; Aloy, Patrick; Cusick, Michael E; Xia, Yu; Roth, Frederick P; Vidal, Marc
    Abstract In cellular systems, biophysical interactions between macromolecules underlie a complex web of functional interactions. How biophysical and functional networks are coordinated, whether all biophysical interactions correspond to functional interactions, and how such biophysical‐versus‐functional network coordination is shaped by evolutionary forces are all largely unanswered questions. Here, we investigate these questions using an “inter‐interactome” approach. We systematically probed the yeast and human proteomes for interactions between proteins from these two species and functionally characterized the resulting inter‐interactome network. After a billion years of evolutionary divergence, the yeast and human proteomes are still capable of forming a biophysical network with properties that resemble those of intra‐species networks. Although substantially reduced relative to intra‐species networks, the levels of functional overlap in the yeast–human inter‐interactome network uncover significant remnants of co‐functionality widely preserved in the two proteomes beyond human–yeast homologs. Our data support evolutionary selection against biophysical interactions between proteins with little or no co‐functionality. Such non‐functional interactions, however, represent a reservoir from which nascent functional interactions may arise.
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    Therapeutic potential of targeting microRNA‐10b in established intracranial glioblastoma: first steps toward the clinic
    (John Wiley and Sons Inc., 2016) Teplyuk, Nadiya M; Uhlmann, Erik; Gabriely, Galina; Volfovsky, Natalia; Wang, Yang; Teng, Jian; Karmali, Priya; Marcusson, Eric; Peter, Merlene; Mohan, Athul; Kraytsberg, Yevgenya; Cialic, Ron; Chiocca, E Antonio; Godlewski, Jakub; Tannous, Bakhos; Krichevsky, Anna
    Abstract MicroRNA‐10b (miR‐10b) is a unique oncogenic miRNA that is highly expressed in all GBM subtypes, while absent in normal neuroglial cells of the brain. miR‐10b inhibition strongly impairs proliferation and survival of cultured glioma cells, including glioma‐initiating stem‐like cells (GSC). Although several miR‐10b targets have been identified previously, the common mechanism conferring the miR‐10b‐sustained viability of GSC is unknown. Here, we demonstrate that in heterogeneous GSC, miR‐10b regulates cell cycle and alternative splicing, often through the non‐canonical targeting via 5′UTRs of its target genes, including MBNL1‐3, SART3, and RSRC1. We have further assessed the inhibition of miR‐10b in intracranial human GSC‐derived xenograft and murine GL261 allograft models in athymic and immunocompetent mice. Three delivery routes for the miR‐10b antisense oligonucleotide inhibitors (ASO), direct intratumoral injections, continuous osmotic delivery, and systemic intravenous injections, have been explored. In all cases, the treatment with miR‐10b ASO led to targets’ derepression, and attenuated growth and progression of established intracranial GBM. No significant systemic toxicity was observed upon ASO administration by local or systemic routes. Our results indicate that miR‐10b is a promising candidate for the development of targeted therapies against all GBM subtypes.
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    Coding and noncoding landscape of extracellular RNA released by human glioma stem cells
    (Nature Publishing Group UK, 2017) Wei, Zhiyun; Batagov, Arsen O.; Schinelli, Sergio; Wang, Jintu; Wang, Yang; El Fatimy, Rachid; Rabinovsky, Rosalia; Balaj, Leonora; Chen, Clark C.; Hochberg, Fred; Carter, Bob; Breakefield, Xandra; Krichevsky, Anna
    Tumor-released RNA may mediate intercellular communication and serve as biomarkers. Here we develop a protocol enabling quantitative, minimally biased analysis of extracellular RNAs (exRNAs) associated with microvesicles, exosomes (collectively called EVs), and ribonucleoproteins (RNPs). The exRNA complexes isolated from patient-derived glioma stem-like cultures exhibit distinct compositions, with microvesicles most closely reflecting cellular transcriptome. exRNA is enriched in small ncRNAs, such as miRNAs in exosomes, and precisely processed tRNA and Y RNA fragments in EVs and exRNPs. EV-enclosed mRNAs are mostly fragmented, and UTRs enriched; nevertheless, some full-length mRNAs are present. Overall, there is less than one copy of non-rRNA per EV. Our results suggest that massive EV/exRNA uptake would be required to ensure functional impact of transferred RNA on brain recipient cells and predict the most impactful miRNAs in such conditions. This study also provides a catalog of diverse exRNAs useful for biomarker discovery and validates its feasibility on cerebrospinal fluid.