Sophina attended Chaminade University in Honolulu from 2009-2013 where she majored in Forensic Science. During her undergraduate degree she was accepted into the Minority Access Program of the Endocrine Society giving her the opportunity to engage in research at the University of Colorado Anshutz Medical Campus and the University of California, San Diego. Using the work done at these universities, she was accepted for a poster presentation at the Annual Biomedical Research Conference for Minority Students 2011 and 2012. She was awarded a Student Presentation award in the Cancer Biology category for an exemplary poster presentation at the 2011 conference. In her senior year she was awarded Chaminade's the highest academic honor, the President Sue Wesselkamper Prize. Sophina graduated Magna Cum Laude in 2013 earning her BS in Forensic Science with minors in chemistry and biology. The following fall she began her pursuit of a PhD in Immunology at the University of Michigan.
Asthma is an inflammatory disease of the airways brought on by the inhalation of environmental allergens. These allergens initiate an inappropriate immune response dominated by the T helper subset Th2 and may also involve Th17 and Th9. Th2 cells act as the main conductor of the immune response in asthma and are therefore a major target in the efforts to treat and prevent this disease. Blockade of Th2 and Th17 cytokines or the skewing of the response toward Th1 or Tregs has been shown to be preventative of asthma. However, since these antigen specific T cells are not eliminated they can potentially return to a Th2 phenotype and cause disease. Targeting these antigen specific T cells for removal using a subset of regulatory B cells is the goal of this proposal. Killer B cells are a subset of regulatory B cells which express the death inducing molecule Fas ligand (FasL). B cells are the main FasL expressing lymphocyte in the lungs and spleens of mice and are enriched in the CD5+CD1dhi population of B1-a cells. Our lab has found these B cells to have effective killing ability against T cells in an antigen specific manner. B1-a cells recognize lipids and carbohydrate moieties of glycoproteins and glycolipids present on most allergens. The antigen specificity of their killing and natural tendency to recognize allergens suggests Killer B cells could play a role in controlling asthma severity. Apoptosis is an important mechanism in controlling asthma with an increase in chronicity correlating with reduced apoptosis in the lung. FasL neutralization in a mouse model of asthma resulted in elevated eosinophil counts in the lung and increased activation of T cells. Further, in a chronic asthma model CD5+ B cells were found to be the necessary cell population for Th cell apoptosis in the lung. In the absence of the CD5+ B cells the mice had increased lung inflammation, interstitial eosinophilia, and mucus and cytokine production with no increase in Th cell apoptosis seen in wild type mice. Killer B cells can be expanded in vitro by stimulation of splenic B cells with IL-5 and CD40L. This culture condition also induces IL-10 production from a separate subset of regulatory B cells. Interestingly, another Th2 cytokine, IL-4, not only supports the growth of a pro-inflammatory B cell population, but potently blocks the effects of IL-5. Th2 cytokines are reported to be cooperative in most situations however, for killer B cells IL-4 is antagonistic to the supportive role of IL-5. Using this in vitro system and adoptive transfer we will test the hypothesis that the elimination of Th cells using killer B cells is an effective treatment for asthma.
2011 Student Presentation award in Cancer Biology, ABRCMS
2013 President Sue Wesselkamper Prize, Chaminade
2013 Rackham Merit Fellowship, University of Michigan
Wang, Q., Chuikov, S., Taitano, S., Wu, Q., Rastogi, A., Tuck, S. J., … Mao-Draayer, Y. (2015). Dimethyl Fumarate Protects Neural Stem/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1/2 MAPK Pathway. International Journal of Molecular Sciences, 16(6), 13885–13907. http://doi.org/10.3390/ijms160613885
Stolberg, V., McCubbrey, A., Freeman, C., Brown, J., Crudgington, S., Taitano, S., Saxton, B., Mancuso, P., Curtis, J., (2015). Glucocorticoid-Augmented Efferocytosis Inhibits Pulmonary Pneumococcal Clearance in Mice by Reducing Alveolar Macrophage Bactericidal Function. Journal of Immunology, 195(1), 174-184