Harrison Thorn, a graduate student in the Pharmaceutical Sciences PhD program at the University of Tennessee Health Science Center, has been awarded an $80,792 grant from the National Institute of Allergy and Infectious Diseases for his work to develop new treatment strategies for a dangerous and often deadly fungal infection.
Conducted under the mentorship of Jarrod Fortwendel, PhD, professor and director of the Center for Pediatric Experimental Therapeutics in the Department of Clinical Pharmacy and Translational Science, Thorn’s research focuses on invasive pulmonary aspergillosis, a life-threatening lung infection caused by the fungus Aspergillus fumigatus, which impacts highly immunocompromised populations.
This infection can be lethal even when properly treated, with death rates reaching as high as 90%. Current antifungal treatments are often ineffective, and resistance to these drugs is growing, making the need for new therapeutic strategies urgent.
Echinocandins, a class of antifungal drugs, are commonly used to treat invasive fungal infections but have limitations against A. fumigatus. While they are generally safe, they fail to fully kill this fungus, especially at high doses where they may paradoxically encourage fungal growth. Thorn’s research aims to make these drugs more effective by targeting the fungus’s internal machinery for cell division, which involves the construction of cross-walls called septa.
“By understanding how A. fumigatus builds and maintains septa during infection, we hope to find ways to make existing antifungal drugs hit harder and work better,” Thorn said.
Dr. Fortwendel’s lab discovered that certain fungal proteins—part of a system called the Septation Initiation Network—are essential for the formation of septa. Disabling one of these key proteins, known as SidB, or its partner MobA, not only weakened the fungus in animal experiments but also made it much more vulnerable to echinocandin treatment.
“This opens a new door for antifungal drug development,” Thorn explained. “If we can block these proteins or their interactions, we might boost the effectiveness of drugs we already have.”
Over the course of the project, Thorn will investigate how these proteins function and how they help the fungus resist treatment. The ultimate goal is to lay the groundwork for next-generation antifungal therapies that could save lives.