Stanford Advisors

All Publications

  • Transcriptomic similarities and differences in host response between SARS-CoV-2 and other viral infections. iScience Thair, S. A., He, Y. D., Hasin-Brumshtein, Y., Sakaram, S., Pandya, R., Toh, J., Rawling, D., Remmel, M., Coyle, S., Dalekos, G. N., Koutsodimitropoulos, I., Vlachogianni, G., Gkeka, E., Karakike, E., Damoraki, G., Antonakos, N., Khatri, P., Giamarellos-Bourboulis, E. J., Sweeney, T. E. 2021; 24 (1): 101947


    The pandemic 2019 novel coronavirus disease (COVID-19) shares certain clinical characteristics with other acute viral infections. We studied the whole-blood transcriptomic host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using RNAseq from 24 healthy controls and 62 prospectively enrolled patients with COVID-19. We then compared these data to non-COVID-19 viral infections, curated from 23 independent studies profiling 1,855 blood samples covering six viruses (influenza, respiratory syncytial virus (RSV), human rhinovirus (HRV), severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), Ebola, dengue). We show gene expression changes in COVID-19 versus non-COVID-19 viral infections are highly correlated (r= 0.74, p< 0.001). However, we also found 416 genes specific to COVID-19. Inspection of top genes revealed dynamic immune evasion and counter host responses specific to COVID-19. Statistical deconvolution of cell proportions maps many cell type proportions concordantly shifting. Discordantly increased in COVID-19 were CD56bright natural killer cells and M2 macrophages. The concordant and discordant responses mapped out here provide a window to explore the pathophysiology of the host response to SARS-CoV-2.

    View details for DOI 10.1016/j.isci.2020.101947

    View details for PubMedID 33437935

  • High-resolution phenotyping of early acute rejection reveals a conserved alloimmune signature. Cell reports Harden, J. T., Wang, X. n., Toh, J. n., Sang, A. X., Brown, R. A., Esquivel, C. O., Martinez, O. M., Krams, S. M. 2021; 34 (9): 108806


    Alloimmune responses in acute rejection are complex, involving multiple interacting cell types and pathways. Deep profiling of these cell types has been limited by technology that lacks the capacity to resolve this high dimensionality. Single-cell mass cytometry is used to characterize the alloimmune response in early acute rejection, measuring 37 parameters simultaneously, across multiple time points in two models: a murine cardiac and vascularized composite allotransplant (VCA). Semi-supervised hierarchical clustering is used to group related cell types defined by combinatorial expression of surface and intracellular proteins, along with markers of effector function and activation. This expression profile is mapped to visualize changes in antigen composition across cell types, revealing phenotypic signatures in alloimmune T cells, natural killer (NK) cells, and myeloid subsets that are conserved and that firmly distinguish rejecting from non-rejecting grafts. These data provide a comprehensive, high-dimensional profile of cellular rejection after allograft transplantation.

    View details for DOI 10.1016/j.celrep.2021.108806

    View details for PubMedID 33657374

  • Genomic variations in EBNA3C of EBV associate with posttransplant lymphoproliferative disorder. JCI insight Maloney, E. M., Busque, V. A., Hui, S. T., Toh, J. n., Fernandez-Vina, M. n., Krams, S. M., Esquivel, C. O., Martinez, O. M. 2020; 5 (6)


    Epstein-Barr Virus (EBV) is a ubiquitous virus linked to a variety of lymphoid and epithelial malignancies. In solid organ and hematopoietic stem cell transplant recipients, EBV is causally associated with posttransplant lymphoproliferative disorder (PTLD), a group of heterogeneous lymphoid diseases. EBV+ B cell lymphomas that develop in the context of PTLD are generally attributed to the immunosuppression required to promote graft survival, but little is known regarding the role of EBV genome diversity in the development of malignancy. We deep-sequenced the EBV genome from the peripheral blood of 18 solid organ transplant recipients, including 6 PTLD patients. Sequences from 6 EBV+ spontaneous lymphoblastoid B cell lines (SLCL) were similarly analyzed. The EBV genome from PTLD patients had a significantly greater number of variations than EBV from transplant recipients without PTLD. Importantly, there were 15 nonsynonymous variations, including 8 in the latent cycle gene EBNA3C that were associated with the development of PTLD. One of the nonsynonymous variations in EBNA3C is located within a previously defined T cell epitope. These findings suggest that variations in the EBV genome can contribute to the pathogenesis of PTLD.

    View details for DOI 10.1172/jci.insight.131644

    View details for PubMedID 32213705

  • Identification of Slug and SOX7 as transcriptional repressors binding to the hepatitis B virus core promoter JOURNAL OF HEPATOLOGY Ko, H., Lam, T., Ng, H., Toh, J., Wang, L., Ren, E. 2018; 68 (1): 42–52