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.
|Haynes, Winston A; Vallania, Francesco; Liu, Charles et al. (2016) EMPOWERING MULTI-COHORT GENE EXPRESSION ANALYSIS TO INCREASE REPRODUCIBILITY. Pac Symp Biocomput 22:144-153|
|Fragiadakis, Gabriela K; Baca, Quentin J; Gherardini, Pier Federico et al. (2016) Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy. J Immunol 197:4482-4492|
|Sharon, Eilon; Sibener, Leah V; Battle, Alexis et al. (2016) Genetic variation in MHC proteins is associated with T cell receptor expression biases. Nat Genet 48:995-1002|
|Adams, Jarrett J; Narayanan, Samanthi; Birnbaum, Michael E et al. (2016) Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity. Nat Immunol 17:87-94|
|Rubelt, Florian; Bolen, Christopher R; McGuire, Helen M et al. (2016) Individual heritable differences result in unique cell lymphocyte receptor repertoires of naÃ¯ve and antigen-experienced cells. Nat Commun 7:11112|
|Angst, Martin S; Fragiadakis, Gabriela K; GaudilliÃ¨re, Brice et al. (2016) In Reply. Anesthesiology 124:1414-5|
|Holmes, Tyson H; He, Xiao-Song (2016) Human immunophenotyping via low-variance, low-bias, interpretive regression modeling of small, wide data sets: Application to aging and immune response to influenza vaccination. J Immunol Methods 437:1-12|
|Frei, Andreas P; Bava, Felice-Alessio; Zunder, Eli R et al. (2016) Highly multiplexed simultaneous detection of RNAs and proteins in single cells. Nat Methods 13:269-75|
|Sweeney, Timothy E; Braviak, Lindsay; Tato, Cristina M et al. (2016) Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis. Lancet Respir Med 4:213-24|
|Kovats, S; Turner, S; Simmons, A et al. (2016) West Nile virus-infected human dendritic cells fail to fully activate invariant natural killer T cells. Clin Exp Immunol 186:214-226|
Showing the most recent 10 out of 158 publications