Biochemistry Professor Awarded R01 Grant to Research Drug-Resistance in Fungal Peptides  

Over the past two years, individuals around the world have gained a better understanding of infectious diseases as a result of the COVID-19 pandemic – and each day, scientists work together with one goal in mind: to outsmart disease mutations that are causing increasing resistance.

That same scientific challenge of resistance is the day-to-day reality behind the work of Gregory Wiedman, Ph.D., assistant professor of biochemistry and chemical biology in the College of Arts and Sciences. In fact, Wiedman has received part of a five-year National Institutes of Health Research Project Grant (R01) to alleviate drug resistance in fungi – specifically the highly-drug registrant pathogen, Cryptococcus neoformans.

R01 grants are the oldest grant mechanism used by the National Institutes of Health (NIH) and provide support for health-related research based on the mission of the NIH.

In partnership with collaborating laboratories and grant recipients from Rutgers University, the project aims to understand a novel mechanism of antifungal drug resistance and ultimately, develop antibody-based disease prevention and control strategies.

As co-investigator, Wiedman’s portion will focus on generating and characterizing peptides and proteins that could improve the delivery of a third-class of antifungal drugs called echinocandins. The work was inspired by the doctoral dissertation of alumnus Robert J. Tancer, Ph.D. in Chemistry '22, who developed a lead compound peptide antifungal drug top potentially improve treatment of the pathogen as part of the 3B Biochemistry, Biophysics, and Biomaterials Lab at Seton Hall University.

“Our collaborators at Rutgers University will look specifically at the genetics and mechanisms behind how our peptides work, giving us feedback on whether or not its application is effective,” commented Wiedman. “In turn, our end focuses on the chemistry sides of things. We take their feedback and use it to design new peptides or improve what we are currently working on.”

Cryptococcus neoformans is a deadly fungal disease that is difficult to treat with limited treatment options. According to the Center for Disease Control and Prevention, infections are rare in people who are otherwise healthy, and most cases occur in people who have weakened immune systems, particularly those who have advanced HIV/AIDS. Current regimens are either highly toxic or inhibit the growth of the fungi, necessitating long treatment regimens which can induce drug resistance.

While Wiedman’s research specifically explored this pathogen, the project’s findings have the potential to inform how scientists look at drug delivery for fungi as a whole.

“Presently, there are only three or four main classes of antifungal drugs, and antimicrobial resistance isn’t stopping anytime soon. Microbes will continue to become more and more resistant to existing drugs. So, our goal is to try and head off its impending rise by exploring new pathways to prevent drug resistance,” added Wiedman.

Students interested in this research area or opportunities to contribute to the grant are encouraged to reach out to Professor Wiedman at [email protected], or check out the 3B Lab website for more information.

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