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Smith, Jennifer

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Smith

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Jennifer

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Smith, Jennifer

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2014 - 20173

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Author's Publications: search.filters.isAuthorOfPublication.278f4947-5908-4708-b6ef-7a942810ab6e

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    RNAi Screening Comes of Age: Improved Techniques and Complementary Approaches
    (Springer Science and Business Media LLC, 2014-09) Mohr, Stephanie; Smith, Jennifer; Shamu, Caroline; Neumüller, Ralph A.; Perrimon, Norbert
    Gene silencing through sequence-specific targeting of mRNAs by RNAi has enabled genome-wide functional screens in cultured cells and in vivo in model organisms. These screens have resulted in the identification of new cellular pathways and potential drug targets. Considerable progress has been made to improve the quality of RNAi screen data through the development of new experimental and bioinformatics approaches. The recent availability of genome-editing strategies, such as the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system, when combined with RNAi, could lead to further improvements in screen data quality and follow-up experiments, thus promoting our understanding of gene function and gene regulatory networks.
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    RNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling
    (Nature Publishing Group UK, 2017) Fu, Bishi; Zhao, Mengmeng; Wang, Lingyan; Patil, Girish; Smith, Jennifer; Juncadella, Ignacio J.; Zuvela-Jelaska, Ljiljana; Dorf, Martin; Li, Shitao
    Interferon regulatory factor 5 (IRF5) is a key transcription factor of innate immunity, which plays an important role in host restriction to viral infection and inflammation. Genome-wide association studies have implied the association of IRF5 with several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjogren’s syndrome, inflammatory bowel disease and multiple sclerosis. However, the regulation of IRF5-mediated immunity is not well understood. To uncover new regulators in IRF5 pathway, we used two “omics” approaches: affinity purification coupled with mass spectrometry and a high throughput RNAi screen. Proteomics identified 16 new IRF5 interactors while RNAi-mediated knockdown found 43 regulators of the TLR7-dependent IRF5 signaling pathway. NXF1 was identified in both screens. Stimulation with TLR7 ligand enhances formation of IRF5-NXF1 protein complexes. Gain or loss-of-function experiments revealed NXF1 selectively regulates TLR7-driven IRF5 transcriptional activity, suggesting a new role for NXF1 in the IRF5 signaling pathway.
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    Knocking down the obstacles to functional genomics data sharing
    (Nature Publishing Group, 2017) Simpson, Kaylene J.; Smith, Jennifer
    This week, Scientific Data published a collection of eight papers that describe datasets from high-throughput functional genomics screens, primarily utilizing RNA interference (RNAi). The publications explore host-pathogen dependencies, innate immune response, disease pathways, and cell morphology and motility at the genome-level. All data, including raw images from the high content screens, are publically available in PubChem BioAssay, figshare, Harvard Dataverse or the Image Data Resource (IDR). Detailed data descriptors enable use of these data for analysis algorithm design, machine learning, data comparisons, as well as generating new scientific hypotheses.