Stephanie Silva-Del Toro
I am interested in understanding how Helicobacter pylori modulates neutrophil phenotype and function and the mechanisms and consequences of N1 subtype differentiation. More specifically, I want to:
1) Elucidate the mechanism of nuclear hypersegmentation. A normal neutrophil nucleus contains 3-4 lobes, but 6-17 lobes per nucleus are observed following H. pylori infection. Mechanisms that control neutrophil nuclear morphology are not well understood. During my rotation project I found that transient hypersegmentation can be induced by staurosporine, a broad spectrum protein kinase inhibitor. I now have preliminary data to suggest a role for classical PKC isoforms in this process, which is consistent with the ability of PKC to modulate the nuclear lamina. Also, microtubule dynamics seem to be involved in neutrophil nuclear morphology. Future studies will focus on analysis of signaling, PKC localization, and its interactions with lamin B2, the lamin B receptor and the cytoskeleton during H. pylori infection.
2) Determine the effects of H. pylori-infected neutrophils on T cell proliferation and function. The N1 neutrophil phenotype was identified first in humans with acute endotoxemia. Analysis of these neutrophils ex vivo showed that were immunosuppressive as indicated by reduced capacity of kill bacteria, inhibition of T-cell proliferation, and altered cytokine production. Thus, we have established a collaboration with Dr. Jon Houtman to analyze effects of H. pylori-infected neutrophils on human T-cell function and hypothesize that H. pylori is may act via host or bacteria arginases or via reactive oxygen species to alter T cell responses. We will also assess cell bacteriocidal capacity and determine the cytokine profile of infected neutrophils assessing gene expression. These studies will provide new insight into the ability of H. pylori to manipulate the human immune response and establish a chronic infection.
3) Understand the mechanisms of neutrophil apoptosis inhibition by H. pylori. Recent data from the Allen lab show that H. pylori also extends neutrophil lifespan, and infected cells remain alive for at least 3 days after infection. As neutrophil lifespan is regulated at the level of transcription to characterize effects of H. pylori on the neutrophil transcriptome using RNA-Seq.
Honors and Awards
- NFS GRFP pre-doc fellowship
- AIC Wallace travel award
- Best poster award at the society of leukocyte biology conference October 2018
- May 2019 I won 3rd best microscopy picture in the Society of Leukocyte Biology Annual Microscopy Picture Competition
- Sloan Scholar Fellowship
- 2019 SACNAS Student Presentation Award at the SACNAS conference in Anaheim, CA