- Adviser: Aaron J. Johnson, Ph.D.
- Area of emphasis: Molecular virology (host-pathogen interaction)
- Research areas: Virology, neuroscience, immunology
What are your research interests?
My thesis research focuses on the role of a pore-forming molecule called perforin and its role in mediating blood-brain barrier disruption during acute central nervous system viral infection.
Perforin is found in the killer cells of the immune system (CD8 T cells and NK cells) and is necessary for pathologic blood-brain barrier disruption. Interestingly, perforin is a highly polymorphic molecule. These polymorphisms can lead to mutations, which can decrease — but not abolish — the activity of perforin. How or why the plethora of mutations exists in perforin is not known.
We put forward the theory that perforin mutations may help mediate the extent of blood-brain barrier disruption. In essence, we are pursuing the "Goldilocks theory" for this molecule, suggesting that at a middle level of perforin activity, there will be some nonpathologic blood-brain barrier disruption and some, but not complete, control of virus infection.
In order to explore this question, we use technologies such as small animal MRI, flow cytometry, gene therapy approaches in mice, RT-PCR, plaque assays, confocal microscopy and 2-photon microscopy.
In sum, this project is multidisciplinary (neuroscience, immunology and virology), has a basic science component (understanding perforin) and a highly translatable aspect (human perforin mutations conferring protective phenotype against blood-brain barrier disruption disease — that is, hemorrhagic fevers).
Why did you choose Mayo Clinic Graduate School of Biomedical Sciences' Virology and Gene Therapy track?
I chose Mayo Clinic Graduate School of Biomedical Sciences' Virology and Gene Therapy track for a variety of reasons. I appreciated the focused yet interdisciplinary work surrounding the program and graduate school in general.
Additionally, the faculty truly seemed excited to mentor students and assist trainees in becoming the best at what they want to do, whether a traditional academic principal investigator career route or something slightly more unorthodox. Also, the facilities, equipment and opportunities available to graduate students could not be matched.
- Willenbring R, Jin F, Huggins M, Hansen M, Johnson A.Perforin and the 3 B's: Mediating pathological disruption of the blood-brain barrier. Presentation at: Autumn Immunology Conference; 2015; Chicago, Ill.
- Johnson H, Willenbring R, Jin F, Manhart W, LaFrance SJ, Pirko I, Johnson A. Perforin competent CD8 T cells are sufficient to cause immune mediated blood brain barrier disruption. Presentation at: Autumn Immunology Conference; 2014; Chicago, Ill.
- Making the most out of opportunities: My journey through the McNair Scholars program. Presentation at: Xcel! Research Scholars Program Orientation; 2014; University of St. Thomas, St. Paul, Minn.
Nov. 17, 2015