Exploring rare diseases: Ashley Zolfaghari investigates biomarkers for Niemann-Pick Type C

Author: John LeSage

Ashley Zolfaghari

The sunny city of San Diego, California might be known for surfing and hiking, but for Ashley Zolfaghari, it was her entry point into an interest in scientific research that she’s cultivated ever since.

“My journey with research started when I was pretty young,” said Zolfaghari, now a senior biology major working in the lab of Kevin Vaughan, associate professor in the Department of Biological Sciences. “I got started when I was in high school. Since I’m from San Diego, there’s a lot of biotech companies and labs that had the opportunity for me to get involved with them, and I absolutely fell in love with doing hands-on research. So when I came to Notre Dame, that was something I was looking for right away.”

During high school, Zolfaghari had been fortunate enough to participate in multiple research programs. Her first experience was a vector cloning project with the Scripps Institute of Oceanography at the University of San Diego, where she learned research techniques such as working with DNA, growing bacteria, and doing polymerase chain reactions (PCR). The following summer, she took an internship at The Scripps Research Translational Institute to work with Kristian Andersen, professor in their Department of Immunology and Microbiology, to study the functional evolution of the Zika virus.

“That was my first introduction to virology and disease research,” Zolfaghari said. “That made me like research a whole lot more, since it was super applicable to people … understanding the big Zika outbreaks of 2014 and 2017.”

Taking these initial interests with her, Zolfaghari connected with Vaughan soon after her arrival at Notre Dame, and found herself involved in even more disease research. Vaughan’s lab researches Niemann-Pick Type C disease, a rare genetic disorder that causes cholesterol to accumulate in the lysosomes and destroy Purkinje cells in the brain’s cerebellum.

“These cells are responsible for important functions like balance, motor control, and memory, so a lot of the symptoms we see in Niemann-Pick-affected people involve loss of balance, difficulty walking and swallowing, and overall control over motor functions becoming limited,” said Zolfaghari.

Unfortunately, these conditions, with the cognitive decline that accompanies them, are also seen in many other diseases such as dementia — often resulting in a misdiagnosis or a delay in finding the problem until it’s too late.

“A lot of patients don’t get diagnosed for an average of seven years, and the median age of death is 13.” she said. “So once you have a diagnosis, you really can’t do anything to help the patient.”

However, Zolfaghari, researching mice that have been genetically altered to have this disease, has made some interesting discoveries that ultimately may allow doctors to diagnose it quickly and correctly, without a slow and expensive genetic screening.

“My project … ultimately resulted from one specific paper published a couple years ago, linking an immune pathway called STING [Stimulation of Interferon Genes] to Niemann-Pick Type C. My thoughts were: we have this paper that links this pathway to the disease … so if there’s any way this pathway could be used as a biomarker, that could help a lot with diagnosis or monitoring the disease.”

And indeed, there was. Zolfaghari determined that the presence of a biomarker known as phosphorylated STING protein increased in the cerebellums of Niemann-Pick-affected mouse models versus unaffected ones. It’s an exciting breakthrough, she described, but more research still needs to be done — there’s a lot between this discovery and any human treatments.

However, that doesn’t mean her work is finished yet.

“One thing I’m doing right now to inform the field of what’s going on is authoring a review article about this pathway, getting the field up to date about the pathway and what happens with it, since this connection isn’t well recognized right now. Once people understand this, Niemann-Pick Type C might be easier to recognize and treat,” said Zolfaghari.

Zolfaghari described that her research has helped her out in many ways, especially looking towards the future and building her Notre Dame network.

“It’s given me a really cool opportunity to connect with a lot of the ND faculty, the grad students in my lab, and also to get really interesting translational, hands-on experience,” she said. “I also had the ability to design my study myself…That really added to my ND education since it taught me how to go about conducting my own research in case you want to do it yourself someday. What might that look like for me, going into grad school where I have to decide my own project?”

She plans to pursue her doctorate degree in biomedical sciences at Vanderbilt University, and doesn’t plan to stop her research anytime soon.

She, like many others who have participated in undergraduate research, recommends it for all students.

“It’s a great way to learn about science in an area that you’re interested in,” she said. “Also, doing hands-on research allows you to discern … Do you like problem-solving? Do you like answering questions? Do you like independence? Do you like collaborating with a team?

“I really see no downside to research,” she added. “It’s fun, it’s interesting, and you get to learn a lot.”