Wednesday, May 8, 2024

The World Health Organization lists Cryptococcus as a fungal priority pathogen to guide research, development, and public health action.

Andrew Jezewski

In extreme cases, Cryptococcus is breathed into the lungs before traveling to the spinal cord and brain, causing cryptococcal meningitis -- an infection that is fatal if untreated.

Andrew Jezewski, a postdoctoral fellow in the Krysan Lab in the Stead Family Department of Pediatrics at the University of Iowa, studies how Cryptococcus grows in the human host. Specifically, Jezewski investigates how the fungus grows in the brain and how it tolerates carbon dioxide. Jezewski estimates that carbon dioxide levels are 100-fold higher in the human body than in the environment.

“Most strains of Cryptococcus don’t grow well in the human body,” Jezewski says. “If that strain gets in your lungs, chances are it won’t survive. It’s a stress on Cryptococcus to encounter substantial amounts of carbon dioxide. But a few strains can resist that stress from carbon dioxide. I am trying figure out how those strains can tolerate that carbon dioxide stress because those are the strains that cause severe disease.”

Cryptococcus isn’t passed from human to human and almost never causes disease in immunocompetent individuals. This alleviates concern when Jezewski and his advisor, Damian Krysan, a professor of pediatric-infectious diseases, work with Cryptococcus that has been isolated from an individual patient. 

People with cryptococcal meningitis can experience seizures and may require cerebral spinal fluid drainage. They are treated intravenously with the antifungal medication amphotericin BJezewski says there around 200,000 cases of cryptococcal meningitis worldwide, with 150,000 resulting in death. 

Since the World Health Organization lists cryptococcus as a fungal priority pathogen, resources are being increased in resource-impoverished areas, so amphotericin B can be more widely prescribed to patients. Researchers like Krysan and Jezewski are also working to identify novel therapeutic strategies.

Grant writing perfection

Jezewski received a rare perfect score on his National Institutes of Health K22 grant application, which will support his research as a faculty member.

I circulated that grant with a lot of people who had won K awards before and got helpful feedback,” Jezewski says. “I took all the feedback to heart to try and improve my grant. My grant received a perfect score in the first round, so I didn’t have to do a resubmission.”

Jezewski plans to take his K22 award, worth $250,000 over two years, with him to his faculty position.

“This shows, as proof of concept, I am competitive in writing grants. When I apply for positions, which are dependent on writing grants, I can at least show I have a record of that,” Jezewski says. “You can take that money to help get your research off the ground in combination with any start-up package you get. When you get offered a start-up package from an institution, (the employer) must show the NIH that the (new hire) is receiving the same level of support that they would give a faculty member who is not receiving a grant.”

Krysan believes that new faculty members doing research must learn to write and communicate their ideas effectively. 

“Andrew has expansive curiosity and creativity. However, one must be able to convince others that what you are interested in and how you will study it are significant and feasible,” Krysan says. “He has written grant proposals at multiple times during his training, culminating with a perfect score on his NIH K22 application; the evolution of his writing and his ability to express his creativity and insights have been gratifying to watch and read.”

 In the upcoming academic year, Jezewski will be joining the Department of Genetics and Biochemistry at Clemson University as an assistant professor affiliated with the nationally renowned Eukaryotic Pathogens Innovation Center (EPIC). His research will focus on Cryptococcus, but he also has prior experience working with other eukaryotic pathogens, including Plasmodium, the causative agent of malaria, and the brain parasite Toxoplasma.

“I am excited to bring my expertise to this new role and collaborate with a distinguished group of faculty," Jezewski says. "Together, we aim to advance our understanding of neglected and complex pathogens, ultimately working toward novel therapeutic strategies.”