The Axon Investigator

Driven by a childhood desire to know what makes us unique, Corey Cusack, PhD, came to UNC to uncover the inner workings of brain cells. This year she earned her doctorate by parsing the tiny proteins involved in neuron death and axon pruning.

Corey Cusack, PhD/Photo by Mark Derewicz, UNC Health Care

Name: Corey Cusack              

Birthdate: February 12, 1986

Hometown: Millstone, NJ

Education: BA, neuroscience, Drew University, 2008 / PhD, neurobiology, UNC, 2014

Dissertation: The molecular intersection between axon pruning and neural apoptosis

Awards: 2013 UNC Impact Award, Pre-doctoral Ruth L. Kirschstein National Research Service Award, Federation of European Neurosciences International Travel Award, Student Speakership for Pierre Morell Research Day

Mentor: Mohanish Deshmukh, PhD

Goal: To determine if neurons use the same pathways during axon pruning—which we need to establish precise brain circuitry—and neuronal cell death—which we need to avoid after early development.

Extracurriculars: Morehead Planetarium Science Ambassador, Carolina KickStart eTeams, GPSF senator, Women in Science planning committee, science policy advocacy, painting, kayaking, trail running, cooking, and reading

History:

“I wasn’t a science kid at all; my brother was the one asking Santa Claus for a microscope. I just wanted to paint and draw and read. I loved making up stories, and my teachers would always say, ‘Corey, you’re going to be a writer someday.’ In high school, I wanted to be an artist. My mother was an artist, but she told me, ‘It’s a hard life, being an artist. Maybe you should keep art as that cup of tea, that thing you can always use to center yourself. Go see what else might be out there for you.’”

Undergraduate research:

“At Drew University I had the most amazing experience. I had free reign in a lab, and professors would ask, ‘What are your questions, what do you want to know, and what do you want to learn how to do? We’ll help you as much as we can.’”

“So I began studying neurobiology as an undergraduate and worked with Dr. Roger Knowles, an Alzheimer’s expert. I was able to isolate primary neurons from animals, culture the cells, stain them, image them, measure them. I realized that all of the treatments we give patients started in a lab. I wanted to contribute to that!”

Why UNC?

“My senior year at Drew, I went to the Society for Neuroscience meeting in San Diego around the time I was applying to graduate schools. I sought out student presenters who currently attended the schools I was applying to. I’d listen to them talk about their research and ask them how they liked their programs, what it was like to live where they do, and how their training experiences were going so far.”

“Hands down, UNC was the winner. The three UNC students I spoke with were the happiest out of everyone I met, and they had only good things to say about the program. The research environment and community at UNC sounded great, and I confirmed this in person during my campus interview. Students from other schools often said that they felt like cogs in a wheel, part of a research ‘factory’. Grad students are incredibly honest with potential recruits; whether they are happy or miserable, they’ll always tell you.

“So I applied to UNC, got in, and that was that. It was my top choice.

“I was part of the very first class in the Biological and Biomedical Sciences Program (BBSP), and the diversity was phenomenal. I learned so much about different disciplines within science and had an opportunity to interact with students in many other departments.”

Why the Deshmukh lab?

“During my second rotation, I worked in Mohanish Deshmukh’s lab where they study how neurons die as well as how they evade death. I knew that this was the lab I wanted to join when I applied to UNC. I had my heart set on it - I knew UNC was trying to improve their research in the area of neurodegenerative diseases, and I wanted to be a part of that.

Why neurodegenerative diseases?

“I had always had been interested in what made people unique, and during my senior year of high school I learned about my family’s history of Alzheimer’s disease. During summers in college, I worked with Alzheimer’s patients in nursing homes and performed experiments in the lab. I read all I could find in the scientific literature about the disease, which people live with for many years; the body is there but everything that makes the person unique slowly slips away. It’s absolutely heartbreaking.

“This is the reason why I wanted to understand how neurons die.”

Dissertation on neuron death

“When scientists study how neurons die, they typically put a neuron in a dish, treat the entire cell, and the entire thing – including its arm-like projections called axons – will die. But if you want to study how only one projection degenerates, you can’t dump a compound on the entire cell and expect to learn anything about how one part of the cell breaks down.

“This is important because as the brain develops, it trims away unnecessary or misprojecting axons in a process called pruning. It helps to think about it like pruning the branches of a tree. In the brain, defects in pruning have been linked to conditions such as autism, schizophrenia, and neurodegenerative diseases. My goal was to find a way to separate whole-cell degeneration from axon-specific degeneration, or pruning.

“I needed a system that would allow me to study the proteins involved in pruning. This system didn’t exist in the lab, but then I heard about microfluidic technology. This technology allows you to culture neurons in one compartment and, over a few days, the neurons’ axons grow through tiny grooves into another compartment. The compartments are fluidically isolated, which allowed me to treat the axons and cell bodies differently during experiments. I went to David Ginty’s lab Johns Hopkins during my second year at UNC to learn this technique. Then I came back and collaborated with Mike Ramsey and Hamp Henley in the UNC chemistry department [in the College of Arts and Sciences] to engineer the microfluidic chambers.

What did you find?

"We found that neurons use some of the same proteins for axon pruning and cell death, which was surprising. In fact, when we were trying to publish the results, other scientists questioned why neurons would use proteins that kick start destruction in only the axons. How does this not trigger total cell death? How does a neuron compartmentalize this process to just the axon?

“We found that some caspases and other key apoptotic proteins work beyond the cell-death pathway. They have other regulatory roles. I studied four different proteins that are all required for apoptosis – Bax, Apaf-1, caspase-9, and caspase-3 – and found that all except Apaf-1 are also required for pruning. I also identified some key players – a protein called XIAP, the proteasome, and neuronal maturation – that help compartmentalize destructive proteins to axons to prevent their lethal spread to the cell body.

“It’s as if the neuron pulls up a drawbridge around the cell body to permit axon pruning without risking cell death.

“These findings are not the ‘key to Alzheimer’s’ or any other degenerative disorder. It’s a little piece of the puzzle that many, many researchers are still putting together. There’s so much that we still don’t understand about how neurons degenerate, whether it’s the entire cell or only a small projecting axon. My work at UNC has been independent of any disease. I just wanted to understand what happens in the brain during normal development. How can you try to fix something if you don’t first understand how it works?”

The future:

“I’ve always been drawn to telling people about research and why it’s important, especially those who aren’t scientists. I have found that people are genuinely curious and excited about science, especially children. I believe that understanding science is like understanding a new language, and scientists need to do a much better job breaking down their jargon and explaining their work to the public in more accessible, relatable ways. I hope to help bridge the gap between scientists in the lab or the field and everyone else.

“After ten straight years at the bench and an intense summer teaching neuroscience as a Duke TIP instructor at Rice University, I am taking a step back before I begin my next chapter. I am very excited to take what I have learned here and tackle something new, such as working as a liaison between science -- such as at a museum, learning center, or non-profit -- funding sources, and the general public.

“The brain truly is the new frontier. We’ve spent a lot of time learning about how the lung works, how the kidneys work, how the heart works. But the brain, we really don’t know much about it. I cannot wait to see what we will find over the next several decades.”

Read more about Corey Cusack’s work.

Media Contact: Mark Derewicz, 919-923-0959, mark.derewicz@unchealth.unc

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