New Drug Targets for Cerebral Malaria

How did you choose your research project and what biomedical issues did you address?

When I came to Mayo, I sought out areas of research that I felt were new and exciting, and I chose the field of neuroimmunology.

My thesis work addressed how the immune system contributes to the development of a disease known as cerebral malaria. Malaria is the deadliest infectious disease worldwide. It's caused by a parasite infection in the blood, but 90% of deaths are due to swelling and inflammation in the brain. Very little is known about how this blood infection causes disease in the brain.

In my research, I've been able to show that during infection, the cells that line the blood vessels of the brain become abnormally activated. This causes them to express elevated levels of molecules called MHC Class I, which interact with immune cells called CD8 T cells and instruct the CD8 T cells to do damage. I also found that two types of Class I molecules prompt distinct responses in the brain, including different onset of symptoms and patterns of disease.

In other experiments, I addressed what happens in the brain after the CD8 T cells are weaponized. I found CD8 T cells prompt neurons to overproduce a molecule called vascular endothelial growth factor, or VEGF, which causes the blood-brain barrier to leak blood into the brain, a hallmark symptom of cerebral malaria. This work allowed me to introduce a two-hit hypothesis about the inflammatory process in the brain: first, the interaction of CD8 T cells with Class I on brain vasculature, and, subsequently, VEGF production by neurons to induce blood-brain barrier disruption.

We have several papers currently in submission describing this work. Importantly, the findings present two, new potential drug targets. In the future, Dr. Johnson's lab will focus on strategies to block Class I and VEGF, aiming to stop brain involvement from occurring or keep symptoms from worsening.

What opportunities at Mayo Clinic Graduate School of Biomedical Sciences did you take advantage of to further your leadership skills and your career path?

The Initiative for Maximizing Student Development fellowship at Mayo does a great job preparing people for leadership positions. The program set me up for the leadership roles I've held, including national liaison for Mayo Society for Advancement of Chicanos/Hispanics and Native Americans in Science (SACNAS) chapter and president of Mayo Women in Science and Engineering Research (WiSER).

What motivates you?

I want to impact people's lives through my research. My family also is one of my biggest motivators. My atypical educational journey began later in life. I am first-gen everything and a mom of three. My goal is for my kids to see that if you set your mind to something, even if it seems impossible, you can achieve it.