Systemic fungal infections cause more than one million deaths annually, and treatments against these infections are often not effective due to drug resistance or toxicity. Maurizio Del Poeta, MD, a Professor in the Department of Molecular Genetics & Microbiology at Stony Brook University, expects to change the landscape of treatment against fungal infections with new approaches based on his laboratory research and collaborative work with fungal experts worldwide. Recognizing the widespread need for better antifungal treatments and the promise of Dr. Del Poeta’s work, the National Institutes of Health (NIH) is funding his research with two grants totaling $6 million.
Dr. Del Poeta’s laboratory largely uses the fungus Cryptococcus neoformans to test new treatment avenues and potential vaccines. C neformans is a pathogen that causes dangerous and often lethal infections, such ascryptococcal meningitis,particularly in ummunosuppressed patients such as those with cancer or HIV/AIDS.
Pioneering work led Dr. Del Poeta and colleagues to identify sphingolipids – membrane lipids essential to many physiological cellular functions – as key regulators of cryptococcal pathogenesis. This finding opened the door to identifying a new approach different from any of the three leading class of antifungal agents used to for decades to treat systemic fungal infections. The findings were reported in a 2015 mBio paper.
“We discovered that one of these sphingolipids, glucosylceramide, is essential for fungal cell replication during infection,” said Dr. Del Poeta. “We then identified a new class of antifungal compounds that inhibit the synthesis of glucosylceramide and thus prevents replication and therefore the infectious process.”
The first NIH grant ($3 million), issued in 2015 and funded over five years, will help to further advance the development of these compounds with the goal to identify a lead compound to be used in clinical trials.
Effective this July, Dr. Del Poeta and colleagues will receive another $3 million five-year NIH grant to support the development a fungal vaccine his lab has created. While vaccine strategies have proven to be transformative against certain bacteria and viruses, there is yet to be an effective fungal vaccine.
The fungal vaccine identified by Dr. Del Poeta is a live attenuated strain that that induces protection against cryptococcal infection in immunocompetent and immunocompromised patients.
“What is extremely promising is that the vaccine appears to protect hosts in the condition of CD4+ T cell deficiency, suggesting it may suitable for HIV positive patients,” said Dr. Del Poeta. The research team will use the grant to study the mechanisms of protection of this new vaccine, particularly when CD4 + T cells are absent. They will also test multiple formulations using only certain parts of the live attenuated strain, an important step to assess safety of the vaccine.
“Fungal disease is an underappreciated cause of death and disability globally,” said Peter Small, MD, the Jim and Robin Hernstein Chair and Founding Director of the Global Health Institute at Stony Brook University. “The work of this interdisciplinary team could spawn new drugs and vaccines that could transform the world’s ability to combat this scourge.”
Dr. Del Poeta will collaborate with scientists at Stony Brook University, such as Dr. Iwao Ojima, Director of the Institute of Chemical Biology and Drug Discovery, and investigators at the University of Cincinnati for the development of the new class of antifungal agents. He will also collaborate with Dr. Ojima and Stony Brook colleagues in the Department of Molecular Genetics and Microbiology, the Division of Infectious Diseases, and the Center for Biotechnology to advance the vaccine research.