INSIGHTS INTO ALS ACCOMPANIED INSIGHTS INTO LIFE FOR UARIZONA HONORS STUDENT

Each time you run an experiment, you have to have a hypothesis, calculate any risks, and be confident in your skills. Now add a layer of thought that these tissues you are working with are priceless donations that have finite stock. Each time more tissue comes into the lab, someone has passed away.

These are the stakes when performing research on postmortem human tissue. Heather Kwapiszeski, a sophomore studying Neuroscience and Cognitive Science at the University of Arizona, spent the 2021 summer at Barrow Neurological Institute in Dr. Robert Bowser’s research laboratory under the mentorship of Dr. Nadine Bakkar doing just that. Drs. Bakkar and Bowser study Amyotrophic Lateral Sclerosis (ALS).

ALS is a fatal neurodegenerative disease that attacks the motor neurons. Ninety percent of all ALS cases are sporadic, meaning that the patients do not have any family history of the disease. Unfortunately, the specific cause of ALS is unknown in these cases. Focusing on disease pathology is key to sorting out how the disease works, and what can be done to stop it. One piece of the pathology is neuroinflammation, a natural immune response to injury that can become harmful.

The choroid plexus (CP) is located in the ventricles, empty space, of the brain. A couple of the main functions of this tissue are to secrete cerebrospinal fluid into that empty space and to separate the blood from the cerebrospinal fluid by making up the Blood Cerebrospinal Fluid Barrier.

The CP is also a gatekeeper and will allow specific immune cells to enter the central nervous system, the brain and spine. All of this means that when the brain is injured, the choroid plexus is calling all of the “warriors” and opening the door for them, so that they can help fight off the injury.

As one of the projects in Dr. Bowser’s lab, Dr. Bakkar and Kwapiszeski investigated inflammatory signals in the choroid plexus of ALS patients and other neurodegenerative diseases.

Bakkar and Kwapiszeski found that there are global alterations to the CP between ALS and Frontotemporal Dementia (FTD). The results show an increase in the level of macrophages, trash clearing immune cells, that are permitted to enter the choroid plexus in ALS compared to control, FTD, and Alzheimer's Disease (AD) in postmortem human tissue.

These results reinforce the choroid plexus’s critical role in trafficking of immune cells and that neuroinflammation and the CP require more research across neurodegenerative diseases.

However, Kwapiszeski mentions that ALS was not the only thing she learned over her time at Barrow. She highlighted how much this experience has impacted her growth as a scientist and as a human being.

Kwapiszeski, who turned 20 this summer, said, “People always ask if you feel older on your birthday. This year that was the case for me, largely due to my internship.”

As part of the lab, Kwapiszeski was involved with the logistics of a research laboratory. She described how the lab environment was very welcoming and supportive, but with an air of professionalism that you do not experience in a typical first job.

Another aspect that made this opportunity so great for Kwapiszeski was the resilience and patience that she was able to practice. Science revolves around questions and not always getting the answers that you wanted.

“You try to answer one question and end up with ten more,” said Dr. Bakkar.

This process of assessing and trying new experiments time and time again instills a resilience in scientists. Even in the brief amount of time that Kwapiszeski was working at Barrow, she saw and bolstered her own strength and determination.

These traits apply outside the benchwork and laboratory, to life as a whole. “Even though I am not sure what I want to do with my life, I have greater confidence that whatever I choose, I will have the gumption to persevere and I realize that there are always new opportunities to pursue what I find interesting,” said Kwapiszeski.

Overall, Kwapiszeski mentioned how grateful she was to have the opportunity to grow intellectually and personally this summer. Her insights into ALS will hopefully help spur future discoveries, and her insights into life have already made a positive difference.
Kwapiszeski would like to thank Barrow Neurological Institute, all those in Dr. Bakkar and Bowser’s Laboratory, University of Arizona Undergraduate Biology Research Program, and Dr. Hildebrand for making this summer possible.