Intracellular protein levels, subcellular localization, or activation state are reflective of a cell's functions. Some relevant cell populations are so rare as to make their isolation for standard biochemical analysis essentially impossible. We have previously shown that disease-driven, single-cell intrinsic events can have profound effects on phospho-signaling network architecture and this can be correlated to clinical outcomes. In the case of viral infection, it is unclear whether or not certain individuals possess immune characteristics that make them more or less susceptible to influenza infection. For instance, environmental or individual characteristics such as age and immune system health could have effects upon the immune system's response to viral challenge. We will document the signaling biology of the immune system at two levels of resolution. First, we will investigate and document the changes to immune signaling post-influenza infection of human PBMC in vitro. These studies allow for analysis of influenza infection and the changes that it creates in immune cell subsets at a single cell level. Second, we will study the signaling biology of PBMC in age-selected cohorts of healthy subjects, including monozygotic twins, given either of the two licensed influenza vaccines (TIV or LAIV). These studies provide a fuller understanding of how immune system changes in the young, the healthy adult, and the elderly individual might account for differing response patterns to alternative vaccine strategies and provide in-sights about influenza effects upon signaling behaviors of immune system cells.
The age-driven differences we have already observed in signaling and the potent changes in the signaling of immune response profiles in PBMC infected with influenza, demonstrates this project will enhance our mechanistic understanding of influenza and its interaction with the immune system, and could identify new tools for clinical differential diagnosis. Such studies could provide means to measure responses to influenza infection and approaches to better manage influenza infection with vaccination or drug intervention.
|Ju, Chia-Hsin; Blum, Lisa K; Kongpachith, Sarah et al. (2018) Plasmablast antibody repertoires in elderly influenza vaccine responders exhibit restricted diversity but increased breadth of binding across influenza strains. Clin Immunol 193:70-79|
|Sweeney, Timothy E; Perumal, Thanneer M; Henao, Ricardo et al. (2018) A community approach to mortality prediction in sepsis via gene expression analysis. Nat Commun 9:694|
|Davis, Mark M; Tato, Cristina M (2018) Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? Seeing the Forest Rather than a Few Trees. Cold Spring Harb Perspect Biol 10:|
|Gee, Marvin H; Han, Arnold; Lofgren, Shane M et al. (2018) Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes. Cell 172:549-563.e16|
|Keeffe, Jennifer R; Van Rompay, Koen K A; Olsen, Priscilla C et al. (2018) A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates. Cell Rep 25:1385-1394.e7|
|Wagar, Lisa E; DiFazio, Robert M; Davis, Mark M (2018) Advanced model systems and tools for basic and translational human immunology. Genome Med 10:73|
|Good, Zinaida; Sarno, Jolanda; Jager, Astraea et al. (2018) Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse. Nat Med 24:474-483|
|Satpathy, Ansuman T; Saligrama, Naresha; Buenrostro, Jason D et al. (2018) Transcript-indexed ATAC-seq for precision immune profiling. Nat Med 24:580-590|
|Vallania, Francesco; Tam, Andrew; Lofgren, Shane et al. (2018) Leveraging heterogeneity across multiple datasets increases cell-mixture deconvolution accuracy and reduces biological and technical biases. Nat Commun 9:4735|
|Bongen, Erika; Vallania, Francesco; Utz, Paul J et al. (2018) KLRD1-expressing natural killer cells predict influenza susceptibility. Genome Med 10:45|
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