Heart failure impacts sixty-four million people worldwide, of which half die within five years of diagnosis. Heart failure occurs when the heart muscle cannot pump enough blood and oxygen to meet the body's needs.

Chiara Borrelli, a doctoral candidate in the Neuroscience Interdisciplinary Graduate Program, focuses her research on the brain’s regulation of breathing and sleeping in people with heart failure. Specifically, this native of Naples, Italy, studies the role played by serotonin, an intriguing potential therapeutic target for this disease. Serotonin is a chemical that carries messages between nerve cells, telling the body how to perform various functions.

“We think that people with heart failure are super sensitive to carbon dioxide. Even tiny amounts of carbon dioxide cause fast breathing in people. Then, their bodies get rid of too much carbon dioxide, and they stop breathing.”

Associated breathing and sleeping disorders are among the causes of increased mortality and decreased quality of life in people with heart failure. About half of all patients suffer from a respiratory disorder called central apneas, which are sudden breathing interruptions caused by an increased sensitivity to carbon dioxide.

“Serotonin promotes breathing and regulates the response by which you adapt your breathing to get rid of excessive carbon dioxide is regulated by this chemical,” Borrelli says. “People normally have a variable response to carbon dioxide. We think that people with heart failure are super sensitive to carbon dioxide. Even tiny amounts of carbon dioxide cause fast breathing in people. Then, their bodies get rid of too much carbon dioxide, and they stop breathing.

As soon as the carbon dioxide raises a bit, patients breathe excessively again. They have this alternating pattern of breathing fast, then not breathing at all.”

Borrelli, a member of Professor George Richerson‘s lab, is examining if medical drugs that act on serotonin can allow patients to breathe more regularly, instead of not excessively or not at all. She is studying mouse models with heart failure and more apneas, with early results showing that reducing serotonin levels decrease apneas. Borrelli is testing to determine if this due to either carbon dioxide sensitivity or substantial amounts of serotonin. 

“Serotonin promotes breathing and is responsible for a physiological response that we call chemoreflex,” Borrelli says. “Chemoreflex response is altered in heart failure, and I don’t know yet if itis because of more serotonin or less serotonin or because people are just more sensitive to it.” 

The Iowa connection 

Halfway through medical school at the University of Pisa, Italian researchers introduced Borrelli to the health issue that she researches today and remains dear to her heart. Borrelli’s grandfather was a neurologist who died from a heart attack that resulted from heart disease.

“Through the serendipity of life, I found this project where you combine brain and cardiovascular disease,” Borrelli says. “The brain regulates breathing, and breathing is affected in many cardiac patients. That was the perfect connection, so I started studying humans to understand their breathing issues.”

Then, Borrelli became aware of Professor Richerson’s research at the University of Iowa. After studying his research papers, Borrelli reached out and asked if she could use her travel abroad stipend to come to the UI to study under him.

Borrelli spent a month in Richerson’s lab in 2016 and two weeks in 2019. 

““I am impressed how (UI Professor George Richerson) approaches a problem and how he comes up with experiments to address the research question. The experiments are simple and beautiful. They are crystal clear for the reader.”

While in Iowa City, Borrelli, under Richerson’s guidance, designed a study for when she returned to Italy, whereby they treated heart failure patients with the anxiety-reducing drug buspirone, which acts on the serotonin system in the brain. 

“I am impressed how (Richerson) approaches a problem and how he comes up with experiments to address the research question,” Borrelli says. “The experiments are simple and beautiful. They are crystal clear for the reader.”

Upon returning to Italy, Borrelli and her colleagues studied if serotonin could play a role in the increased response to carbon dioxide and apneas in heart failure patients. They used buspirone because serotonin acting agents treat anxiety and depression.

“We saw that patients’ sensitivity to carbon dioxide was reduced, and the apneas were reduced, too,” Borrelli says.

From research to bedside 

Borrelli’s life goal is to translate her research from bench to bedside.  She wants to work in a critical care setting—mirroring her time as an emergency medicine physician at the University of Pisa from 2018-2023. For Borrelli, establishing a respectful relationship with her patients carries immense importance.

“You must find a way to connect with different personalities, with different diseases,” Borrelli says. “I saw how social my work can be, how I can be very impactful on peoples’ lives quickly.”

After earning her doctorate, Borrelli would like to practice medicine and conduct research in the United States.

“There’s really no time for research (in Italy), which is one of the reasons why I came to the University of Iowa,” Borrelli says. “I needed time to really understand the research.”

Under Richerson’s guidance, Borrelli has developed into a top physician scientist.