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  1. Article ; Online: Single-Cell RNA Sequencing of Tocilizumab-Treated Peripheral Blood Mononuclear Cells as an in vitro Model of Inflammation

    Arya Zarinsefat / George Hartoularos / Dmitry Rychkov / Priyanka Rashmi / Sindhu Chandran / Flavio Vincenti / Chun J. Yee / Minnie M. Sarwal

    Frontiers in Genetics, Vol

    2021  Volume 11

    Abstract: COVID-19 has posed a significant threat to global health. Early data has revealed that IL-6, a key regulatory cytokine, plays an important role in the cytokine storm of COVID-19. Multiple trials are therefore looking at the effects of Tocilizumab, an IL- ... ...

    Abstract COVID-19 has posed a significant threat to global health. Early data has revealed that IL-6, a key regulatory cytokine, plays an important role in the cytokine storm of COVID-19. Multiple trials are therefore looking at the effects of Tocilizumab, an IL-6 receptor antibody that inhibits IL-6 activity, on treatment of COVID-19, with promising findings. As part of a clinical trial looking at the effects of Tocilizumab treatment on kidney transplant recipients with subclinical rejection, we performed single-cell RNA sequencing of comparing stimulated PBMCs before and after Tocilizumab treatment. We leveraged this data to create an in vitro cytokine storm model, to better understand the effects of Tocilizumab in the presence of inflammation. Tocilizumab-treated cells had reduced expression of inflammatory-mediated genes and biologic pathways, particularly amongst monocytes. These results support the hypothesis that Tocilizumab may hinder the cytokine storm of COVID-19, through a demonstration of biologic impact at the single-cell level.
    Keywords single cell RNA seq ; COVID-19 ; tocilizumab (IL-6 inhibitor) ; kidney transplantation ; transcriptomics ; bioinformatics and computational biology ; Genetics ; QH426-470
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Plasma proteome perturbation for CMV DNAemia in kidney transplantation.

    Tara K Sigdel / Patrick Boada / Maggie Kerwin / Priyanka Rashmi / David Gjertson / Maura Rossetti / Swastika Sur / Dane Munar / James Cimino / Richard Ahn / Harry Pickering / Subha Sen / Rajesh Parmar / Benoit Fatou / Hanno Steen / Joanna Schaenman / Suphamai Bunnapradist / Elaine F Reed / Minnie M Sarwal /
    CMV Systems Immunobiology Group

    PLoS ONE, Vol 18, Iss 5, p e

    2023  Volume 0285870

    Abstract: Background Cytomegalovirus (CMV) infection, either de novo or as reactivation after allotransplantation and chronic immunosuppression, is recognized to cause detrimental alloimmune effects, inclusive of higher susceptibility to graft rejection and ... ...

    Abstract Background Cytomegalovirus (CMV) infection, either de novo or as reactivation after allotransplantation and chronic immunosuppression, is recognized to cause detrimental alloimmune effects, inclusive of higher susceptibility to graft rejection and substantive impact on chronic graft injury and reduced transplant survival. To obtain further insights into the evolution and pathogenesis of CMV infection in an immunocompromised host we evaluated changes in the circulating host proteome serially, before and after transplantation, and during and after CMV DNA replication (DNAemia), as measured by quantitative polymerase chain reaction (QPCR). Methods LC-MS-based proteomics was conducted on 168 serially banked plasma samples, from 62 propensity score-matched kidney transplant recipients. Patients were stratified by CMV replication status into 31 with CMV DNAemia and 31 without CMV DNAemia. Patients had blood samples drawn at protocol times of 3- and 12-months post-transplant. Additionally, blood samples were also drawn before and 1 week and 1 month after detection of CMV DNAemia. Plasma proteins were analyzed using an LCMS 8060 triple quadrupole mass spectrometer. Further, public transcriptomic data on time matched PBMCs samples from the same patients was utilized to evaluate integrative pathways. Data analysis was conducted using R and Limma. Results Samples were segregated based on their proteomic profiles with respect to their CMV Dnaemia status. A subset of 17 plasma proteins was observed to predict the onset of CMV at 3 months post-transplant enriching platelet degranulation (FDR, 4.83E-06), acute inflammatory response (FDR, 0.0018), blood coagulation (FDR, 0.0018) pathways. An increase in many immune complex proteins were observed at CMV infection. Prior to DNAemia the plasma proteome showed changes in the anti-inflammatory adipokine vaspin (SERPINA12), copper binding protein ceruloplasmin (CP), complement activation (FDR = 0.03), and proteins enriched in the humoral (FDR = 0.01) and innate immune responses (FDR ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Corrigendum

    Tara K. Sigdel / Paul D. Piehowski / Sudeshna Roy / Juliane Liberto / Joshua R. Hansen / Adam C. Swensen / Rui Zhao / Ying Zhu / Priyanka Rashmi / Andrew Schroeder / Izabella Damm / Swastika Sur / Jinghui Luo / Yingbao Yang / Wei-Jun Qian / Minnie M. Sarwal

    Frontiers in Medicine, Vol

    Near-Single-Cell Proteomics Profiling of the Proximal Tubular and Glomerulus of the Normal Human Kidney

    2021  Volume 7

    Keywords glomerulus ; mass spectrometry ; single cell analysis ; proteomics ; kidney ; Medicine (General) ; R5-920
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  4. Article ; Online: Near-Single-Cell Proteomics Profiling of the Proximal Tubular and Glomerulus of the Normal Human Kidney

    Tara K. Sigdel / Paul D. Piehowski / Sudeshna Roy / Juliane Liberto / Joshua R. Hansen / Adam C. Swensen / Rui Zhao / Ying Zhu / Priyanka Rashmi / Andrew Schroeder / Izabella Damm / Swastika Sur / Jinghui Luo / Yingbao Yang / Wei-Jun Qian / Minnie M. Sarwal / The Kidney Precision Medicine Project (KPMP) Consortium

    Frontiers in Medicine, Vol

    2020  Volume 7

    Abstract: Molecular assessments at the single cell level can accelerate biological research by providing detailed assessments of cellular organization and tissue heterogeneity in both disease and health. The human kidney has complex multi-cellular states with ... ...

    Abstract Molecular assessments at the single cell level can accelerate biological research by providing detailed assessments of cellular organization and tissue heterogeneity in both disease and health. The human kidney has complex multi-cellular states with varying functionality, much of which can now be completely harnessed with recent technological advances in tissue proteomics at a near single-cell level. We discuss the foundational steps in the first application of this mass spectrometry (MS) based proteomics method for analysis of sub-sections of the normal human kidney, as part of the Kidney Precision Medicine Project (KPMP). Using ~30–40 laser captured micro-dissected kidney cells, we identified more than 2,500 human proteins, with specificity to the proximal tubular (PT; n = 25 proteins) and glomerular (Glom; n = 67 proteins) regions of the kidney and their unique metabolic functions. This pilot study provides the roadmap for application of our near-single-cell proteomics workflow for analysis of other renal micro-compartments, on a larger scale, to unravel perturbations of renal sub-cellular function in the normal kidney as well as different etiologies of acute and chronic kidney disease.
    Keywords glomerulus ; mass spectrometry ; single cell analysis ; proteomics ; kidney ; Medicine (General) ; R5-920
    Subject code 616
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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