The Pershing Square Foundation Awards $3 Million to Innovative SARS-CoV-2 Research Projects

The Pershing Square Foundation announced that it has awarded $3 million to nineteen recipients at ten academic research institutions conducting research related to the SARS-CoV-2 virus.
[The Pershing Square Foundation]
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T Cell Antigen Discovery

The T cell receptors–peptide-MHC interaction mediates’ between a T cell and its target cell dictates its function and thereby influences its role in disease.
[Nature Metabolism]
Joglekar, A. V., & Li, G. (2020). T cell antigen discovery. Nature Methods, 1–8. https://doi.org/10.1038/s41592-020-0867-z Cite
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AMG-232 Sensitizes High MDM2-Expressing Tumor Cells to T-Cell-Mediated Killing

Ovarian clear cell carcinoma cell lines carrying wild-type p53 with low/high mouse double minute 2 homolog (MDM2) expression were investigated in a T-cell co-culture system evaluating T-cell-mediated tumor killing.
[Cell Death Discovery]
Sahin, I., Zhang, S., Navaraj, A., Zhou, L., Dizon, D., Safran, H., & El-Deiry, W. S. (2020). AMG-232 sensitizes high MDM2-expressing tumor cells to T-cell-mediated killing. Cell Death Discovery, 6(1), 1–7. https://doi.org/10.1038/s41420-020-0292-1 Cite
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Single-Cell Transcriptomics Identifies Multiple Pathways Underlying Antitumor Function of TCR and CD8αβ-Engineered Human CD4+ T Cells

Investigators evaluated the role of mouse double minute 2 homolog (MDM2) in T-cell-mediated immune resistance. Ovarian clear cell carcinoma cell lines carrying wild-type p53 with low/high MDM2 expression were investigated in a T-cell co-culture system evaluating T-cell-mediated tumor killing.
[Science Advances]
Rath, J. A., Bajwa, G., Carreres, B., Hoyer, E., Gruber, I., Martínez-Paniagua, M. A., … Arber, C. (2020). Single-cell transcriptomics identifies multiple pathways underlying antitumor function of TCR- and CD8αβ-engineered human CD4+ T cells. Science Advances, 6(27), eaaz7809. https://doi.org/10.1126/sciadv.aaz7809 Cite
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STIM 1-Mediated Calcium Influx Controls Antifungal Immunity and the Metabolic Function of Non-pathogenic Th17 Cells

Researchers identified patients with a novel mutation in STIM 1 that abolished Ca2+ influx and resulted in increased susceptibility to fungal and other infections.
[EMBO Molecular Medicine]
Kahlfuss, S., Kaufmann, U., Concepcion, A. R., Noyer, L., Raphael, D., Vaeth, M., … Feske, S. (2020). STIM1-mediated calcium influx controls antifungal immunity and the metabolic function of non-pathogenic Th17 cells. EMBO Molecular Medicine, n/a(n/a), e11592. https://doi.org/10.15252/emmm.201911592 Cite
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Marked T Cell Activation, Senescence, Exhaustion and Skewing towards TH17 in Patients with COVID-19 Pneumonia

Investigators showed that, compared with healthy controls, COVID-19 patients’ T cell compartment displayed several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1+CD57+ exhausted T cells.
[Nature Communications]
De Biasi, S., Meschiari, M., Gibellini, L., Bellinazzi, C., Borella, R., Fidanza, L., … Cossarizza, A. (2020). Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia. Nature Communications, 11(1), 3434. https://doi.org/10.1038/s41467-020-17292-4 Cite
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An Evaluation of COVID-19 Serological Assays Informs Future Diagnostics and Exposure Assessment

The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2 had the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies.
[Nature Communications]
GeurtsvanKessel, C. H., Okba, N. M. A., Igloi, Z., Bogers, S., Embregts, C. W. E., Laksono, B. M., … Koopmans, M. (2020). An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment. Nature Communications, 11(1), 3436. https://doi.org/10.1038/s41467-020-17317-y Cite
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The Clinical Course of SARS-CoV-2 Positive Neonates

The authors reviewed relevant literature to understand the clinical course of disease and transmission routes in affected neonates.
[Journal of Perinatology]
De Bernardo, G., Giordano, M., Zollo, G., Chiatto, F., Sordino, D., De Santis, R., & Perrone, S. (2020). The clinical course of SARS-CoV-2 positive neonates. Journal of Perinatology, 1–8. https://doi.org/10.1038/s41372-020-0715-0 Cite
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Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells

Researchers identified circulating CD88CD1c+CD163+ denritic cells (DCs) as immediate precursors of inflammatory CD88CD14+CD1c+CD163+FcεRI+ DCs.
[Immunity]
Bourdely, P., Anselmi, G., Vaivode, K., Ramos, R. N., Missolo-Koussou, Y., Hidalgo, S., … Guermonprez, P. (2020). Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2020.06.002 Cite
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ERMAP Is a B7 Family-Related Molecule That Negatively Regulates T Cell and Macrophage Responses

Scentists identified erythroid membrane-associated protein (ERMAP) as a novel T cell inhibitory molecule. ERMAP shared significant sequence and structural homology with existing B7 family members in its extracellular domain.
[Cellular & Molecular Immunology]
Su, M., Lin, Y., Cui, C., Tian, X., & Lai, L. (2020). ERMAP is a B7 family-related molecule that negatively regulates T cell and macrophage responses. Cellular & Molecular Immunology, 1–14. https://doi.org/10.1038/s41423-020-0494-8 Cite
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Dynamics in Protein Translation Sustaining T Cell Preparedness

Scientists investigated the dynamics of mRNA translation kinetics and protein turnover in human naive and activated T cells.
[Nature Immunology]
Wolf, T., Jin, W., Zoppi, G., Vogel, I. A., Akhmedov, M., Bleck, C. K. E., … Geiger, R. (2020). Dynamics in protein translation sustaining T cell preparedness. Nature Immunology, 1–11. https://doi.org/10.1038/s41590-020-0714-5 Cite
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