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portfolio
publications
Stage-Specific Requirement for Eomes in Mature NK Cell Homeostasis and Cytotoxicity
Published in Cell Reports, 2020
This paper investigates the role of the transcription factor Eomes in the regulation of mature NK cell homeostasis and cytotoxicity. it finds that inducible deletion of Eomes in mature Ncr1+ cells impairs NK cell maturation from Stage II to Stage III and partially abrogates cytotoxic responsiveness.
Recommended citation: Wagner JA, Wong P, Schappe T, et al. Stage-Specific Requirement for Eomes in Mature NK Cell Homeostasis and Cytotoxicity. Cell Rep. 2020;31(9):107720. doi:10.1016/j.celrep.2020.107720 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265846/
Integrated analysis of multimodal single-cell data
Published in Cell, 2021
This paper presents a framework that allows for the integration of multiple data types using single cells. This framework can be applied to understand distinct immune cell states, previously unidentified immune populations, and to interpret immune responses to vaccinations.
Recommended citation: Hao Y, Hao S, Andersen-Nissen E, et al. Integrated analysis of multimodal single-cell data. Cell. 2021;184(13):3573-3587.e29. doi:10.1016/j.cell.2021.04.048 h[ttp://academicpages.github.io/files/paper3.pdf](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238499/)
Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19
Published in Journal of Experimental Medicine, 2021
This paper uses single-cell profiling to explore how dysregulation of the innate immune system is associated with COVID-19 severity. Severe COVID-19 is associated with hyperactivation of neutrophils and NK cells, while monocytes take on tolerogenic phenotypes. Meanwhile, mild COVID-19 is associated with limited, or rapidly resolved, immune perturbation.
Recommended citation: Wilk AJ, Lee MJ, Wei B, et al. Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19. J Exp Med. 2021;218(8):e20210582. doi:10.1084/jem.20210582 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210586/
Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells From HIV+ Controllers and ART-Suppressed Individuals
Published in Frontiers in Immunology, 2022
This paper used CyTOF profiling of paired blood and lymph node samples from aviremic HIV+ individuals to identify unique phenotypic profiles in elite controllers versus ART-suppressed individuals.
Recommended citation: George AF, Luo X, Neidleman J, et al. Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells From HIV+ Controllers and ART-Suppressed Individuals. Front Immunol. 2022;13:803417. Published 2022 Jan 27. doi:10.3389/fimmu.2022.803417 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829545/
Single-cell RNA-seq methods to interrogate virus-host interactions
Published in Seminars in Immunopathology, 2022
This paper reviews how various single-cell RNA sequencing technologies can be leveraged to interrogate virus-host interactions. It aims to provide readers with a comprehensive framework that can assist them in designing scRNA-seq experiments involving viral samples, virally-infected cells, or host cells from infected individuals.
Recommended citation: Ratnasiri K, Wilk AJ, Lee MJ, Khatri P, Blish CA. Single-cell RNA-seq methods to interrogate virus-host interactions. Semin Immunopathol. 2023;45(1):71-89. doi:10.1007/s00281-022-00972-2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684776/
SARS-CoV-2 escapes direct NK cell killing through Nsp1-mediated downregulation of ligands for NKG2D
Published in Cell Reports, 2022
This paper demonstrates that healthy NK cells are unable to efficiently lyse SARS-CoV-2-infected cells, likely due to their loss of the ligands for the activating receptor NKG2D. These effects are mediated by the viral protein Nsp1.
Recommended citation: Lee MJ, Leong MW, Rustagi A, et al. SARS-CoV-2 escapes direct NK cell killing through Nsp1-mediated downregulation of ligands for NKG2D. Cell Rep. 2022;41(13):111892. doi:10.1016/j.celrep.2022.111892 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9742201/
Defining the role of natural killer cells in COVID-19
Published in Nature Immunology, 2023
This paper is a review of the literature relating to the NK cell response in COVID-19.
Recommended citation: Lee, M.J., Blish, C.A. Defining the role of natural killer cells in COVID-19. Nat Immunol (2023). https://doi.org/10.1038/s41590-023-01560-8 https://www.nature.com/articles/s41590-023-01560-8
NK cell-monocyte crosstalk underlies NK cell activation in severe COVID-19
Published in Journal of Immunology, 2024
This paper interrogates communication between NK cells and other peripheral immune cells in severe COVID-19 and demonstrates that monocytes from severe COVID-19 patients are capable of inducing activating in healthy donor NK cells.
Recommended citation: Lee, M. J. et al. NK cell-monocyte crosstalk underlies NK cell activation in severe COVID-19. J Immunol 2024.6.1 212 (11): 1693–1705. doi: 10.4049/jimmunol.2300731. https://journals.aai.org/jimmunol/article/212/11/1693/266801/NK-Cell-Monocyte-Cross-talk-Underlies-NK-Cell
stay-tuned
talks
Assessing the impact of COVID-19 on NK cells
Published:
Severe COVID-19 induces strong alterations in the peripheral immune system. Some immune cell types take on a protective role in this disease, while others contribute to disease pathology. One cell type whose functional role in COVID-19 is not yet known is the natural killer (NK) cell. In order to better understand the NK cell response to this disease, we profiled NK cells and whole PBMC from donors across the COVID-19 severity spectrum using CyTOF, single-cell RNA sequencing, and single-cell ATAC sequencing. We found that severe COVID-19 induces strong activation of peripheral NK cells. The activated NK cells in severe COVID-19 patients also downregulate surface expression, but not transcriptional expression, of the activating receptors DNAM-1 and NKG2D. As both of these receptors can be internalized upon ligation, we assessed expression of the ligands for these receptors on other peripheral immune cells and identified a significant increase in the expression of the ligands for NKG2D and DNAM-1 on the monocytes of severe COVID-19 patients. Collectively, our results suggest that monocytes may activate NK cells via the ligation of activating receptors in severe COVID-19.
Interrogating the natural killer cell response to COVID-19: SARS-CoV-2 modulates ligands for NK cell receptors & escapes NK cell killing
Published:
Severe coronavirus disease 2019 (COVID-19) induces strong alterations in the peripheral immune system. Some immune cell types take on a protective role in this disease, while others contribute to disease pathology. One cell type whose functional role in COVID-19 is not yet known is the natural killer (NK) cell. To investigate this question, we assessed the ability of primary NK cells to respond to A549-ACE2 cells infected with replication-competent SARS-CoV-2, the causative agent of COVID-19. We found striking differences in the ability of NK cells to recognize and kill SARS-CoV-2-infected cells compared to bystander cells. To determine the mechanistic basis for our observations, we interrogated the expression of ligands for NK cell receptors on infected cells and identified significant modulation of multiple ligands on SARS-CoV-2-infected cells. Finally, we screened individual SARS-CoV-2 proteins for the ability to modulate NK cell responses. Collectively, our work reveals that infection of target cells with SARS-CoV-2 alters the NK cell response and elucidates a mechanism by which this may occur.
SARS-CoV-2 modulates ligands for NK cell receptors & escapes NK cell killing
Published:
Severe coronavirus disease 2019 (COVID-19) induces strong alterations in the peripheral immune system. Some immune cell types take on a protective role in this disease, while others contribute to disease pathology. One cell type whose functional role in COVID-19 is not yet known is the natural killer (NK) cell. To investigate this question, we assessed the ability of primary NK cells to respond to A549-ACE2 cells infected with replication-competent SARS-CoV-2, the causative agent of COVID-19. We found striking differences in the ability of NK cells to recognize and kill SARS-CoV-2-infected cells compared to bystander cells. To determine the mechanistic basis for our observations, we interrogated the expression of ligands for NK cell receptors on infected cells and identified significant modulation of multiple ligands on SARS-CoV-2-infected cells. Finally, we screened individual SARS-CoV-2 proteins for the ability to modulate NK cell responses. Collectively, our work reveals that infection of target cells with SARS-CoV-2 alters the NK cell response and elucidates a mechanism by which this may occur.
Interrogating the natural killer cell response to COVID-19: SARS-CoV-2 modulates ligands for NK cell receptors & escapes NK cell killing
Published:
Severe coronavirus disease 2019 (COVID-19) induces strong alterations in the peripheral immune system. Some immune cell types take on a protective role in this disease, while others contribute to disease pathology. One cell type whose functional role in COVID-19 is not yet known is the natural killer (NK) cell. To investigate this question, we assessed the ability of primary NK cells to respond to A549-ACE2 cells infected with replication-competent SARS-CoV-2, the causative agent of COVID-19. We found striking differences in the ability of NK cells to recognize and kill SARS-CoV-2-infected cells compared to bystander cells. To determine the mechanistic basis for our observations, we interrogated the expression of ligands for NK cell receptors on infected cells and identified significant modulation of multiple ligands on SARS-CoV-2-infected cells. Finally, we screened individual SARS-CoV-2 proteins for the ability to modulate NK cell responses. Collectively, our work reveals that infection of target cells with SARS-CoV-2 alters the NK cell response and elucidates a mechanism by which this may occur.