How is nucleic acid sensing related to viral pathogenesis?
Research in the Barker lab is focused on understanding innate immune responses to viral infection. Once a virus infects a cell, the viral genome is released in order to for transcription and viral replication. This viral nucleic acid can also be recognized by pattern recognition receptors to lead to interferon or other inflammatory cytokine production or cell death. These inflammatory responses may be linked to the pathogenesis resulting from the viral infection. Specifically, we are interested in the signaling downstream of DNA sensors as these receptors can bind to HIV and other retroviral reverse transcription products. In addition, we are interested in genetic variation in pattern recognition receptor genes and the relationship between this variation, receptor function, and viral pathogenesis. The goal of these studies is to compare the structure and function of PRRs from species that suffer from AIDS-like immune destruction following HIV/SIV infection and from species that do not suffer from AIDS-like disease following this infection. We hypothesize that differences in PRR activity may underlie this difference in pathology.
* Drew University undergraduate student co-author
Shannon JL*, Murphy MS*, Kantheti U*, Burnett JM*, Hahn MG*, Dorrity TJ*, Bacas CJ*, Mattice EB*, Corpuz KD*, Barker BR. 2018. Polyglutamine binding protein 1 (PQBP1) inhibits innate immune responses to cytosolic DNA. Molecular Immunology. 99: 182-190. doi: 10.1016/j.molimm.2018.05.014.
Wilson JE, Petrucelli AS, Chen L, Koblansky AA, Truax AD, Oyama Y, Rogers AB, Brickey WJ, Wang Y, Schneider M, Mühlbauer M, Chou WC, Barker BR, Jobin C, Allbritton NL, Ramsden DA, Davis BK, Ting JP. 2015. Inflammasome-independent role of AIM2 of suppressing colon tumorigenesis via DNA-PK and Akt. Nature Medicine. 21(8):906-13. doi: 10.1038/nm.3908.
Barker BR. 2013. Evaluation of T cell function in allergic disease. Methods in Molecular Biology.1032:31-44. doi: 10.1007/978-1-62703-496-8_3.
Barker BR. 2013. Measuring T cell function in innate immune models. Methods in Molecular Biology. 1031:77-90. doi: 10.1007/978-1-62703-481-4_10.
Barker BR, Taxman DJ, Ting JP. 2011. Cross-regulation between the IL-1b/IL-18 processing inflammasome and other inflammatory cytokines. Current Opinion in Immunology. 23(5):591-7. doi: 10.1016/j.coi.2011.07.005.
Davis BK, Roberts RA, Huang MT, Willingham SB, Conti BJ, Brickey WJ, Barker BR, Kwan M, Taxman DJ, Accavitti-Loper MA, Duncan JA, Ting JP. 2011. Cutting edge: NLRC5-dependent activation of the inflammasome. Journal of Immunology. 186(3):1333-7. doi: 10.4049/jimmunol.1003111.
Barker BR, Gladstone MN, Gillard GO, Panas MW, Letvin NL. 2010. Critical role for IL-21 in both primary and memory anti-viral CD8+ T-cell responses. European Journal of Immunology.40(11):3085-96. doi: 10.1002/eji.200939939.
Barker BR, Parvani JG, Meyer D, Hey AS, Skak K, Letvin NL. 2007. IL-21 induces apoptosis of antigen-specific CD8+ T lymphocytes. Journal of Immunology. 179(6):3596-603.
Sun Y, Schmitz JE, Buzby AP, Barker BR, Rao SS, Xu L, Yang ZY, Mascola JR, Nabel GJ, Letvin NL. 2006. Virus-specific cellular immune correlates of survival in vaccinated monkeys after simian immunodeficiency virus challenge. Journal of Virology. 80(22):10950-6.
Letvin NL, Mascola JR, Sun Y, Gorgone DA, Buzby AP, Xu L, Yang ZY, Chakrabarti B, Rao SS, Schmitz JE, Montefiori DC, Barker BR, Bookstein FL, Nabel GJ. 2006. Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science. 312(5779):1530-3.
