Mentor: Benjamin Segal, MD
In adoptive transfer models of Experimental Autoimmune Encephalomyelitis (EAE), transfer of WT T-cells specific for the myelin epitope, Myelin Oligodendrocyte Glycoprotein (MOG), into WT mice causes inflammation primarily in the spinal chord. This results in an ascending paralysis in the mice. Adoptive transfers of MOG-specific T-cells from IFNg KO mice into WT mice or WT MOG-specific T-cells into IFNg receptor KO mice results in balance issues beginning with a tilt of the head or leaning to one side often progressing to a 'spinning,' phenotype where the mice continuously spin in one direction on the axis of the head to tail. Since myelinated tracts in distinct regions of the CNS serve distinct functions, we hypothesize that the loss of IFNg changes the localization of inflammation and demyelination to tracts critical for maintaining appropriate balance. My project centers around finding specific mechanisms that explain how IFNg influences the localization of inflammation in adoptive transfer models EAE.
Stoolman, J. S., Vannella, K. M., Coomes, S. M., Wilke, C. A., Sisson, T. H., Toews, G. B., & Moore, B. B. (2011). Latent infection by γherpesvirus stimulates profibrotic mediator release from multiple cell types American journal of physiology. Lung cellular and molecular physiology, 300(2), L274–85. doi:10.1152/ajplung.00028.2010.
Luckhardt TR, Coomes SM, Trujillo G, Stoolman JS, Vannella KM, Bhan U, et al.(2011) TLR9-induced interferon β is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis. Fibrogenesis Tissue Repair. 2011;4:18.
Bauman, K. A., Wettlaufer, S. H., Okunishi, K., Vannella, K. M., Stoolman, J. S., Huang, S. K., Courey, A. J., et al. (2010). The antifibrotic effects of plasminogen activation occur via prostaglandin E2 synthesis in humans and mice The Journal of clinical investigation, 120(6), 1950–1960. doi:10.1172/JCI38369.
Franchi, L., Stoolman, J., Kanneganti, T.-D., Verma, A., Ramphal, R., & Núñez, G. (2007). Critical role for Ipaf in Pseudomonas aeruginosa-induced caspase-1 activation European journal of immunology, 37(11), 3030–3039. doi:10.1002/eji.200737532.
Stoolman JS, Le L, Segal BM. The effects of IFNg signaling on the composition and distribution of CNS infiltrates during EAE. 2012. Multiple Sclerosis Symposium, Ann Arbor, MI.
Naik P, Wilke C, Stoolman JS, Toews G, and B.B. Moore. Gammaherpesvirus infected aged mice have altered fibroblasts and epithelial cells. ATS International Conference, Denver, CO, May 15-18, 2011.
Bauman B, Hubbard LH, Coomes, SM, Vannella, KM, Wilke CA, Stoolman JS, and BB Moore. Susceptibility to P. aeruginosa infection post-BMT is limited to the lung. 2010. American Thoracic Society International Conference, New Orleans, LA.