Healthy Living

Doctor Turns Personal Tragedy Into Fight Against Cystic Fibrosis

Doctor Turns Personal Tragedy Into Fight Against Cystic Fibrosis

Photo: Wanda O'Neal and Michael Knowles, UNC Health Care

Since cystic fibrosis runs in the family, continuously researching news about the disease can help both patients and their families stay up to date on current events, such as new CF medications and treatments. Yet, for one woman, Dr. Wanda O’Neal, merely researching the latest information on CF was not enough.

Wanda had eight siblings, six of whom were diagnosed with cystic fibrosis. Her sister, Nancy, was the first to pass away at the age of eight. “I remember my father got a call from the hospital. It was pneumonia, they told me. They said she choked,” said Wanda. Although Nancy was a young girl, she had been ill for an extended period throughout the course of her life. Even though doctors suspected that she had CF, they did not understand what caused the disease, nor how to treat it. At this point, the family’s doctor recommended that each child undergo testing for CF through a simple sweat test. “I remember that day. It was sad and surreal. We all took our turns going in for the test. My mother kept finding out that another one of her kids had CF. I know that she knew before they told her, because we all knew which kids were thin and which ones coughed a lot. But she still cried,” said Wanda.

What set her brother apart

For the next 16 years, Wanda’s mother took care of her sick children. Yet, despite her endless efforts, four of her children passed away at a young age. Wanda’s brother, Mike, who was also diagnosed with CF, is still living with the disease. “He was never really sick, but he definitely had CF. When my brother Danny died, he was a year younger than Mike but always much sicker. My mom was constantly taking care of Danny and the others, and there was Mike, just hanging out,” said Wanda. Mike has rarely been admitted to a hospital and this led Wanda to wonder what was protecting her brother, more specifically, what set him apart from their other siblings. “We don’t know what. But what if it’s something simple? What if it’s the same thing that protects other CF patients who have milder disease? What if we could find out what it is and exploit that knowledge?” she said.

Wanda’s new life mission

Wanda, wanting to put her personal tragedy into achievement, decided to dedicate her life to researching cystic fibrosis. Her straight As in high school got her accepted into North Dakota State, where her favorite class was biology. During one of her classes, Wanda was first introduced to the topic of genetics. “I just loved the subject. Fundamentally, plant genetics is not much different than human genetics,” she said. After receiving a bachelor’s degree in science, Wanda was accepted into NDSU’s crop-science PhD program. Although she had a true passion for pathology, she admitted to a friend that she did not know what she would do with one more degree. Her friend asked her one simple question and that was what she wanted to do with her life. Without giving it any thought, Wanda answered - “What I really want to do is work on CF.” As this point in her life, Wanda did not realize that what she really wanted was a career as a biomedical researcher. “I had no idea how to even go about it. But it made total sense—the genetics of it, my family, my love of biology. Once I thought of it, there was no turning back,” she said.

Today, Wanda studies the CFTR protein

Today, Wanda is an associate professor of medicine at the Marsico Lung Institute/UNC Cystic Fibrosis Center. She and her fellow colleagues are studying the defective CFTR protein in patients with CF and genetically altering it in the lab to allow it to function better and keep the mucus within the lungs continuously hydrated. In their most recent study, the research team used gene-expression data from cell samples gathered from 750 patients over the last 10 years. They then proceeded to analyze over 4,000 genetic pathways to find which ones played a vital role in the development of CF. They uncovered two significant genetic pathways: HLA pathways and endomembrane pathways, and found that the severity of the disease greatly depends on how these pathways function. More specifically, they found that when the pathways produced a higher amount of proteins, patients with CF experienced less severe symptoms. Yet, when the pathways produced a lower amount of proteins, patients with CF experienced more severe symptoms. “Now that we’ve found these pathways, we need to dig into the biology to see how specific genes within the pathways influence disease severity. We hope we can target these genes to limit the severity of disease. If so, this could help all patients in a big way,” said Wanda.

Making treatment unique for CF patients

Furthermore, the researchers at UNC are working alongside pharmaceutical companies to develop treatments that could make the defective CFTR protein function properly in patients with CF. “We're developing the technology to actually personalize it; to tailor the optimal therapy for that person,” said Dr. Richard Boucher, director at the Marsico Lung Institute/UNC Cystic Fibrosis Center. They are hopeful to raise the age expectancy of CF patients from their forties to their seventies.

Wanda and her fellow colleagues have discovered a potential threat to the development of CF, yet their discovery has a long way to go. In the past, the researchers believed that gene therapy could offer a potential cure, but it turned out that the structure of the genetic disease was far more complicated than they had anticipated. “Science doesn’t seem to work that way. People need to understand the generally slow nature of discovery. But we know more than we did, and we know where to keep looking to understand the disease better,” she said.

For Wanda, being able to research CF and to help improve quality of life for patients living with the disease has been a privilege. “I’m very happy to be a piece of the puzzle. As director of the molecular core here at the CF Center, I’m in a position that allows me to help many people in the research community. Really, with almost anything related to molecular genetics, our core can help. This is a great fit for me,” she said. Wanda also stressed that she will never stop looking for a cure, with the memory of her siblings motivating her to triumph forward. “It’s important for families to know that there are people working on this disease and that we care about it. It’s important to be able to say to your child that there might be a cure—not today or tomorrow—but that good people are working on it and that there is hope. I honestly don’t think this is false hope. I think it’s real, because we’ve come far since I was a kid. I don’t ever want to lose sight of that,” she said.