Chasing a rare disease

Postdoc's personal experience drives research.

When Anthony Anzell, PhD, was a sophomore in high school, a terrible migraine came out of nowhere and lasted for several weeks. His only relief came from sleeping, which he was doing about 21 hours a day.
“I wasn't eating anything,” Anzell, now a postdoctoral fellow in the Department of Human Genetics, recalls of those days in 2007. “I lost somewhere around 40 pounds. Since I didn’t have much weight to lose, my parents were very
, very concerned.”
Despite being told to “wait it out” by his doctors, Anzell’s strong-willed mother pushed for a diagnosis. When it came, they were astounded.
A CT scan revealed a fourth of his brain was covered in abscesses, and he was subsequently diagnosed with a rare genetic disease called hereditary hemorrhagic telangiectasia (teh-lan-jee-ek-TAY-zhuh), or HHT. No one in his family knew what it was, let alone how to pronounce it.
They learned that HHT causes abnormal connections between arteries and veins called arteriovenous malformations (AVMs). The most common locations affected are the nose, lungs, brain and liver.
There are two primary genes responsible for HHT – the endoglin gene and another gene called ACVRL1. Anzell’s genetic test came back positive for a mutation in the endoglin gene.
After undergoing three brain surgeries to remove fluid that had built up in his brain, as well as a liver surgery and lung surgery to seal off two pulmonary AVMs, Anzell began to stabilize.
He soon was inspired to raise awareness and funding for HHT through various activities, one of which was endurance sports. He joined the crew team at Grand Valley State University in Grand Rapids, Mich., as a collegiate rower, and participated in several 50-mile ultramarathons and ultra-ironman competitions throughout his post-college years.
“I started to see my experience as an opportunity to devote my life to something,” he says. Before long, he completed a doctoral degree in physiology at Wayne State University in Detroit.
After graduation, he sought out Beth Roman, PhD, associate professor and vice chair of research in the Department of Human Genetics and basic research director of the school’s HHT Center. Roman, a leading expert in HHT, studies the disease’s molecular and cellular mechanisms.
As a postdoc in Roman’s lab, Anzell has immersed himself in research to understand more about the disease process of HHT, which he hopes will result in new therapies “For the last three and a half years [at Pitt], I've been living out my dream doing HHT research,” he says. “It’s been really amazing.”
Anzell is primarily focused on the cellular biology of AVMs and exploring the role of blood flow in their development.
“We have some data that shows cells move differently when they lose the receptor that is encoded by the gene ACVRL1, which is called ALK1,” he explains. “Instead of moving against blood flow, they may move with the flow of blood, and we think that this somehow leads to AVMs.”
His research received a boost recently with a $20,000 Young Investigator Draft grant from Uplifting Athletes, an organization that uses the platform of college athletics to fund collaborative basic bench research on rare diseases.
A perfect blend of Anzell’s passion for sports and rare disease research, he is using the award to continue his work to better understand how a cell’s structure, shape, size and arrangement changes with HHT.
“The science that we do on these rare diseases doesn’t just help those affected by them, it can apply to almost to any sort of physiology,” he adds. “When we talk about how blood vessels form, that's a natural part of life. Understanding how and why things fail is just as important.”

Anzell remains passionate about raising awareness of HHT. A member of the board of directors for the nonprofit organization Cure HHT, he wants people to know that an estimated 50,000 to 100,000 Americans are affected by HHT, and that the majority of cases go undiagnosed.
“I think the tough thing is that when you see me, you see a very healthy individual, somebody who's very active,” he says. “You don’t see that I have nose bleeds every day. I will obviously have to struggle with this disease for the rest of my life.”

Now a parent of young children, Anzell is thankful for the tenacity of his parents, which brings him to tears. He is also especially grateful that both his children have tested negative for an HHT genetic mutation.

“It started with me and ends with me,” he says. “I feel super blessed to have two really healthy kiddos.” 

-Clare Collins                                                                                                      
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The World Health Organization defines a rare disease as one that affects 1.3 in 2,000 people. The total economic burden of rare diseases in the United States was estimated to be $966 billion in 2019.
Rare Disease Day, a global initiative to raise awareness and support for people on a rare medical journey, takes place on leap day, Thursday, February 29.