Professional Education


  • Doctor of Philosophy, Unlisted School (2017)
  • Master of Science, Unlisted School (2011)
  • Bachelor of Science, Unlisted School (2009)
  • Postdoctoral Fellow, Johns Hopkins University, School of Medicine (2019)

Stanford Advisors


All Publications


  • Macrophage inflammatory and regenerative response periodicity is programmed by cell cycle and chromatin state. Molecular cell Daniel, B., Belk, J. A., Meier, S. L., Chen, A. Y., Sandor, K., Czimmerer, Z., Varga, Z., Bene, K., Buquicchio, F. A., Qi, Y., Kitano, H., Wheeler, J. R., Foster, D. S., Januszyk, M., Longaker, M. T., Chang, H. Y., Satpathy, A. T. 2022

    Abstract

    Cell cycle (CC) facilitates cell division via robust, cyclical gene expression. Protective immunity requires the expansion of pathogen-responsive cell types, but whether CC confers unique gene expression programs that direct the subsequent immunological response remains unclear. Here, we demonstrate that single macrophages (MFs) adopt different plasticity states in CC, which leads to heterogeneous cytokine-induced polarization, priming, and repolarization programs. Specifically, MF plasticity to interferon gamma (IFNG) is substantially reduced during S-G2/M, whereas interleukin 4 (IL-4) induces S-G2/M-biased gene expression, mediated by CC-biased enhancers. Additionally, IL-4 polarization shifts the CC-phase distribution of MFs toward the G2/M phase, providing a subpopulation-specific mechanism for IL-4-induced, dampened IFNG responsiveness. Finally, we demonstrate CC-dependent MF responses in murine and human disease settings invivo, including Th2-driven airway inflammation and pulmonary fibrosis, where MFs express an S-G2/M-biased tissue remodeling gene program. Therefore, MF inflammatory and regenerative responses are gated by CC in a cyclical, phase-dependent manner.

    View details for DOI 10.1016/j.molcel.2022.11.017

    View details for PubMedID 36521490

  • Enhanced T cell effector activity by targeting the Mediator kinase module. Science (New York, N.Y.) Freitas, K. A., Belk, J. A., Sotillo, E., Quinn, P. J., Ramello, M. C., Malipatlolla, M., Daniel, B., Sandor, K., Klysz, D., Bjelajac, J., Xu, P., Burdsall, K. A., Tieu, V., Duong, V. T., Donovan, M. G., Weber, E. W., Chang, H. Y., Majzner, R. G., Espinosa, J. M., Satpathy, A. T., Mackall, C. L. 2022; 378 (6620): eabn5647

    Abstract

    T cells are the major arm of the immune system responsible for controlling and regressing cancers. To identify genes limiting T cell function, we conducted genome-wide CRISPR knockout screens in human chimeric antigen receptor (CAR) T cells. Top hits were MED12 and CCNC, components of the Mediator kinase module. Targeted MED12 deletion enhanced antitumor activity and sustained the effector phenotype in CAR- and T cell receptor-engineered T cells, and inhibition of CDK8/19 kinase activity increased expansion of nonengineered T cells. MED12-deficient T cells manifested increased core Meditator chromatin occupancy at transcriptionally active enhancers-most notably for STAT and AP-1 transcription factors-and increased IL2RA expression and interleukin-2 sensitivity. These results implicate Mediator in T cell effector programming and identify the kinase module as a target for enhancing potency of antitumor T cell responses.

    View details for DOI 10.1126/science.abn5647

    View details for PubMedID 36356142

  • Divergent clonal differentiation trajectories of T cell exhaustion. Nature immunology Daniel, B., Yost, K. E., Hsiung, S., Sandor, K., Xia, Y., Qi, Y., Hiam-Galvez, K. J., Black, M., J Raposo, C., Shi, Q., Meier, S. L., Belk, J. A., Giles, J. R., Wherry, E. J., Chang, H. Y., Egawa, T., Satpathy, A. T. 2022

    Abstract

    Chronic antigen exposure during viral infection or cancer promotes an exhausted T cell (Tex) state with reduced effector function. However, whether all antigen-specific T cell clones follow the same Tex differentiation trajectory remains unclear. Here, we generate a single-cell multiomic atlas of T cell exhaustion in murine chronic viral infection that redefines Tex phenotypic diversity, including two late-stage Tex subsets with either a terminal exhaustion (Texterm) or a killer cell lectin-like receptor-expressing cytotoxic (TexKLR) phenotype. We use paired single-cell RNA and T cell receptor sequencing to uncover clonal differentiation trajectories of Texterm-biased, TexKLR-biased or divergent clones that acquire both phenotypes. We show that high T cell receptor signaling avidity correlates with Texterm, whereas low avidity correlates with effector-like TexKLR fate. Finally, we identify similar clonal differentiation trajectories in human tumor-infiltrating lymphocytes. These findings reveal clonal heterogeneity in the T cell response to chronic antigen that influences Tex fates and persistence.

    View details for DOI 10.1038/s41590-022-01337-5

    View details for PubMedID 36289450

  • BCL6-dependent TCF-1+ progenitor cells maintain effector and helper CD4+ Tcell responses to persistent antigen. Immunity Xia, Y., Sandor, K., Pai, J. A., Daniel, B., Raju, S., Wu, R., Hsiung, S., Qi, Y., Yangdon, T., Okamoto, M., Chou, C., Hiam-Galvez, K. J., Schreiber, R. D., Murphy, K. M., Satpathy, A. T., Egawa, T. 2022

    Abstract

    Soon after activation, CD4+ Tcells are segregated into BCL6+ follicular helper (Tfh) and BCL6- effector (Teff) Tcells. Here, we explored how these subsets are maintained during chronic antigen stimulation using the mouse chronic LCMV infection model. Using single cell-transcriptomic and epigenomic analyses, we identified a population of PD-1+ TCF-1+ CD4+ Tcells with memory-like features. TCR clonal tracing and adoptive transfer experiments demonstrated that these cells have self-renewal capacity and continue to give rise to both Teff and Tfh cells, thus functioning as progenitor cells. Conditional deletion experiments showed Bcl6-dependent development of these progenitors, which were essential for sustaining antigen-specific CD4+ Tcell responses to chronic infection. An analogous CD4+ Tcell population developed in draining lymph nodes in response to tumors. Our study reveals the heterogeneity and plasticity of CD4+ Tcells during persistent antigen exposure and highlights their population dynamics through a stable, bipotent intermediate state.

    View details for DOI 10.1016/j.immuni.2022.05.003

    View details for PubMedID 35637103

  • Mitochondrial variant enrichment from high-throughput single-cell RNA sequencing resolves clonal populations. Nature biotechnology Miller, T. E., Lareau, C. A., Verga, J. A., DePasquale, E. A., Liu, V., Ssozi, D., Sandor, K., Yin, Y., Ludwig, L. S., El Farran, C. A., Morgan, D. M., Satpathy, A. T., Griffin, G. K., Lane, A. A., Love, J. C., Bernstein, B. E., Sankaran, V. G., van Galen, P. 2022

    Abstract

    The combination of single-cell transcriptomics with mitochondrial DNA variant detection can be used to establish lineage relationships in primary human cells, but current methods are not scalable to interrogate complex tissues. Here, we combine common 3' single-cell RNA-sequencing protocols with mitochondrial transcriptome enrichment to increase coverage by more than 50-fold, enabling high-confidence mutation detection. The method successfully identifies skewed immune-cell expansions in primary human clonal hematopoiesis.

    View details for DOI 10.1038/s41587-022-01210-8

    View details for PubMedID 35210612

  • Single-cell multiomics defines tolerogenic extrathymic Aire-expressing populations with unique homology to thymic epithelium. Science immunology Wang, J., Lareau, C. A., Bautista, J. L., Gupta, A. R., Sandor, K., Germino, J., Yin, Y., Arvedson, M. P., Reeder, G. C., Cramer, N. T., Xie, F., Ntranos, V., Satpathy, A. T., Anderson, M. S., Gardner, J. M. 2021; 6 (65): eabl5053

    Abstract

    [Figure: see text].

    View details for DOI 10.1126/sciimmunol.abl5053

    View details for PubMedID 34767455

  • Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling. Science (New York, N.Y.) Weber, E. W., Parker, K. R., Sotillo, E., Lynn, R. C., Anbunathan, H., Lattin, J., Good, Z., Belk, J. A., Daniel, B., Klysz, D., Malipatlolla, M., Xu, P., Bashti, M., Heitzeneder, S., Labanieh, L., Vandris, P., Majzner, R. G., Qi, Y., Sandor, K., Chen, L., Prabhu, S., Gentles, A. J., Wandless, T. J., Satpathy, A. T., Chang, H. Y., Mackall, C. L. 2021; 372 (6537)

    Abstract

    T cell exhaustion limits immune responses against cancer and is a major cause of resistance to chimeric antigen receptor (CAR)-T cell therapeutics. Using murine xenograft models and an in vitro model wherein tonic CAR signaling induces hallmark features of exhaustion, we tested the effect of transient cessation of receptor signaling, or rest, on the development and maintenance of exhaustion. Induction of rest through enforced down-regulation of the CAR protein using a drug-regulatable system or treatment with the multikinase inhibitor dasatinib resulted in the acquisition of a memory-like phenotype, global transcriptional and epigenetic reprogramming, and restored antitumor functionality in exhausted CAR-T cells. This work demonstrates that rest can enhance CAR-T cell efficacy by preventing or reversing exhaustion, and it challenges the notion that exhaustion is an epigenetically fixed state.

    View details for DOI 10.1126/science.aba1786

    View details for PubMedID 33795428

  • Charting a shared epigenetic pathway to CD8+ T cell dysfunction in infection and cancer. Molecular cell Sandor, K., Daniel, B., Satpathy, A. T. 2021; 81 (11): 2272-2274

    Abstract

    Pritykin et al. (2021) establish a comprehensive chromatin atlas of CD8+ T cell dysfunction in chronic viral infection and cancer via analysis of bulk and single-cell ATAC-seq datasets across immune challenges. These results unify the classification scheme and molecular programs driving CD8+ T cell dysfunction across disease settings and will facilitate basic discovery and translational efforts in T cell immunity.

    View details for DOI 10.1016/j.molcel.2021.05.020

    View details for PubMedID 34087178