Creighton researcher awarded $2.9 million NIH grant to study hearing loss
Marisa Zallocchi, PhD, assistant professor of biomedical sciences at Creighton University’s School of Medicine, sees a physiological anomaly and immediately starts asking questions. Why does it exist? What are its underlying causes? She is fascinated with its origin, because if she can understand this, she is that much closer to discovering a cure—or at least arresting its development.
“I have always been drawn to diseases and their underlying causes,” Zallocchi says. It’s why she directed her science education toward research as opposed to practice. She wanted to help develop bodies of knowledge that would inform the way physicians treated patients rather than be the doctor herself.
Zallocchi earned her doctorate from the University of Buenos Aires and came to Creighton in 2019 from Argentina by way of Iowa City, where she was a post-doc fellow, and then Boys Town. She joined Creighton’s biomedical sciences department and the Dr. Richard J. Bellucci Translational Hearing Center to work alongside other research scientists who are developing solutions that preserve or restore hearing and vestibular function.
Zallocchi says she found her research focus in hearing loss by happenstance. As a researcher, her background originally was in kidney function. But her supervisor had begun a new project on hearing loss and invited her to participate. She read up on the topic and was quickly fascinated by what would become her primary research concentration.
It’s proven to be an effective switch. The National Institutes of Health (NIH) has awarded Zallocchi a five-year, $2.9 million R01 grant to study how to counteract the hearing loss associated with aminoglycosides, a specific type of antibiotic, through piperlongumine, a natural compound found in the fruit of the long pepper plant.
“Aminoglycosides are a group of antibiotics widely used to treat infections, especially those caused by drug-resistant bacteria. They are favored for their effectiveness, low cost and the fact that they don’t need refrigeration, which makes them particularly useful in developing countries,” Zallocchi says. “However, a major downside of aminoglycosides is that they can cause permanent hearing loss, and there is currently no treatment to prevent this side effect.”
These broad spectrum, antibacterial antibiotics are commonly used to treat serious infections such as sepsis, tuberculosis, persistent urinary tract infection and E. coli. They are also administered to the infections that frequently plague individuals with immune deficiencies. Drug resistance is another factor in the growing use of aminoglycosides. Increasingly, other antibiotic families, once the go-to treatment, are becoming less effective as infections become resistant to their ability to heal.
Given that 40%-60% of patients experience hearing loss while on aminoglycosides, research that seeks to mitigate this side effect is important.
Piperlongumine is anti-inflammatory in nature. It kills senescent cells, which release chemicals that can cause inflammation and damage nearby healthy cells. The NIH grant will allow Zallocchi and her team to modify piperlongumine’s chemical structure to increase its potency and efficacy while reducing its toxicity.
In the first phase, they will test these modified compounds on zebrafish. If they can block the pathway that is the known route aminoglycosides enter cells, they can reduce hearing loss. The most effective compounds will then be tested on mice to closely mimic this antibiotic’s treatment in humans. Once they identify two or three compounds that are potentially both safe and effective for human use, they will move into the clinical trial phase.
It's a collaborative effort. Zallocchi’s research team, which is comprised of one Creighton undergraduate student, one senior post-doc and a soon-to-be-hired additional post-doc, is working with Creighton’s Department of Pharmacy and a chemist at University of Nebraska Medical Center (UNMC).
“It’s a team effort,” she says, “with each bringing their own specialization to the project.”
“We need more researchers. We don’t have enough,” Zallocchi continues. “The more we discover, the more we can improve the quality of life for others. I’m always trying to recruit students to research.”
