Recent advances in biomedical science have made it possible to perform cell-based genetic screens in mammalian cells to uncover gene-specific functions in a high throughput fashion. These include the sequencing of the human and mouse genomes, the assembly of non-redundant genome-wide collections of cDNAs, the development of RNA interference methods in mammalian cells, and the assembly of genomewide collections of short hairpin RNAs (shRNAs) that can target known genes. The overall goal of the Genomic Resources Core is to facilitate the application of these advances in four projects of the Program, to make it possible to interrogate gene function during T cell receptor (TCR) engagement.and subsequent signaling. The Genomic Resources Core will grant investigators in the program access to cDNA and shRNA libraries that have genomic coverage and which are stored and maintained in the Johns Hopkins High Throughput Biology (HiT) Center. Using facilities in the Pomerantz laboratory, the Genomic Resources Core will provide a centralized facility for processing the bacterial aliquots provided by the HiT Center, including A) preparation of DNA from the bacterial aliquots for transient transfection;B) packaging of shRNA-expressing viral constructs into virus for infection of target cells;C) infection of target cells with packaged virus;D) the transfer of library clone cDNA inserts into appropriate expression vectors for screening;and E) pooling of library clones to maximize the number of genes to be screened per assay. The Genomic Resources Core will allow for unbiased screens for genes that play a role in TCR engagement and signaling, as well as for targeted study of candidate genes that are hypothesized to play critical roles in these processes. Project 1 will use the Core to identify genes involved in TCR clustering during activation. Project 3 will use the Core to test the role of candidate genes involved in the Sproutyl -mediated regulation of TCR signaling. Project 4 will use the Core to survey tyrosine kinase genes for potential roles in TCR-induced calcium signaling. Project 5 will use the Core to identify modulators of TCR signaling to NF-KB. Since inappropriate TCR signaling can result in ineffective immune surveillance, autoimmunity, or cancer, the results of these screening efforts may provide molecular targets for new therapies designed to treat diseases of the immune system.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Special Emphasis Panel (ZAI1)
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Johns Hopkins University
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Schappert, Anna; Schneck, Jonathan P; Suarez, Lauren et al. (2018) Soluble MHC class I complexes for targeted immunotherapy. Life Sci 209:255-258
Hickey, John W; Isser, Ariel Y; Vicente, Fernando P et al. (2018) Efficient magnetic enrichment of antigen-specific T cells by engineering particle properties. Biomaterials 187:105-116
Bettencourt, Ian A; Powell, Jonathan D (2017) Targeting Metabolism as a Novel Therapeutic Approach to Autoimmunity, Inflammation, and Transplantation. J Immunol 198:999-1005
Kosmides, A K; Meyer, R A; Hickey, J W et al. (2017) Biomimetic biodegradable artificial antigen presenting cells synergize with PD-1 blockade to treat melanoma. Biomaterials 118:16-26
Tiper, Irina V; Temkin, Sarah M; Spiegel, Sarah et al. (2016) VEGF Potentiates GD3-Mediated Immunosuppression by Human Ovarian Cancer Cells. Clin Cancer Res 22:4249-58
Pollizzi, Kristen N; Sun, Im-Hong; Patel, Chirag H et al. (2016) Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8(+) T cell differentiation. Nat Immunol 17:704-11
Sch├╝tz, Christian; Varela, Juan Carlos; Perica, Karlo et al. (2016) Antigen-specific T cell Redirectors: a nanoparticle based approach for redirecting T cells. Oncotarget 7:68503-68512
Pollizzi, Kristen N; Patel, Chirag H; Sun, Im-Hong et al. (2015) mTORC1 and mTORC2 selectively regulate CD8? T cell differentiation. J Clin Invest 125:2090-108
Perica, Karlo; Kosmides, Alyssa K; Schneck, Jonathan P (2015) Linking form to function: Biophysical aspects of artificial antigen presenting cell design. Biochim Biophys Acta 1853:781-90
Bruns, Heiko; Bessell, Catherine; Varela, Juan Carlos et al. (2015) CD47 Enhances In Vivo Functionality of Artificial Antigen-Presenting Cells. Clin Cancer Res 21:2075-83

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