Q&A with Neta Shlezinger

Meet the Zuckerman Faculty Scholar Neta Shlezinger at The Hebrew University of Jerusalem, studying “fungal pathogenesis and immune responses

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“I like the proof-of-concept research I call ‘the dark side of science,’ those crazy ideas that sometimes get tested and become well-established ideas.”

Dr. Neta Shlezinger earned her PhD at Tel Aviv University’s George S. Wise Faculty of Life Sciences and did her postdoctoral research at Memorial Sloan Kettering Cancer Center in New York, where she was one of three recipients of their Postdoctoral Research Award out of more than 600 postdoctoral fellows. As a member of the faculty of the Koret School of Veterinary Medicine in the Faculty of Agriculture at the Hebrew University’s Rechovot campus, Dr. Shlezinger applies a multidisciplinary approach in her lab to explore the mechanisms that enable fungi to overcome immune surveillance and cause infectious diseases; and how the host immune response can protect against fungal pathogens.

 Please describe your current research, the focus of your lab, and the practical implications of your research

Fungal pathogens infect over 1 billion human patients and cause nearly 2 million fatalities every year. Due to a combination of limited effective drugs, the rise in at-risk patient populations, and the emergence of multi-drug resistant strains, proper treatment of fungal infections has become a growing health concern. My lab studies fungal pathogens of animals, humans and plants. People inhale pathogenic fungi all the time, and the number of people who die from fungal infections each year is higher than those who die from malaria and breast cancer and is on par with that of tuberculosis and HIV. The entire spectrum of immunocompromised patients is at risk of acquiring fungal infection. This includes cancer, bone marrow and solid transplants, injuries, diabetes, autoimmune disease, and genetic or acquired immunodeficiencies. A very timely example are the staggering numbers of fungal infections in Covid patients that were given steroids to treat the viral infection, but the tradeoff is a deadly fungal infection with a mortality rate of 60% with current treatment.

There’s a silent pandemic right now with the spread of multidrug resistance fungal pathogens, which really threatens the effectiveness of our very limited arsenal of antifungals.  Fungal pathogens present a bigger challenge to that of bacterial pathogens, because they share significant similarities with their hosts, which greatly complicates the task of identifying selective drugs that kill the fungus without harming the infected person, animal or plant.

For this reason, the available antifungal drugs are limited in number and diversity and infections are very difficult to treat, and even worse, fungi rapidly evolve resistance to the drugs we use to kill them. In fact, resistance to every class of antifungal drug has emerged already, and multidrug-resistant superbugs fungi are now spreading all over the world.

To address the emergency of multi-drug resistance in fungi, my team and I try to answer several basic and pressing questions: How do fungal cells die? How does our immune system combat them?  And how can we use this knowledge to develop novel antifungal treatments?

We established a system of color-coded fluorescent biosensors that enable us to visualize individual host-pathogen encounters in real-time during infection. This approach allows us to simultaneously screen hundreds of thousands of genetic elements or drug libraries and determine its action both on the host, the pathogen and the microbial environment.  It was through this technique that I discovered how our innate immune system triggers a programmed cell death mechanism in fungal cells, making them self-destruct through the activation of designated fungal proteins.

I believe that exploring these intricate interactions will advance our understanding of the fascinating biology of fungi, while also pinpointing new targets for the development of much needed new antifungal – and perhaps more generally, antimicrobial – treatments.

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What do you enjoy most about what you do/your research?

I love mentoring my students, to see how they are developing and how their thinking is evolving. I find it very fulfilling. I also love collaborating with colleagues from ally sciences and brainstorming with my team. It’s an opportunity to come up with ideas someone else can get excited about.  I like the initial steps, the proof-of-concept research I call “the dark side of science,” those crazy ideas that sometimes get tested to see if they work. Many well-established ideas come from “the dark side.”

What has it meant to you to be part of the Zuckerman Faculty Scholars Program?

I am new to the program and the past year did not offer many opportunities to get to know one another.  I am enjoying the interactions with colleagues like Ido Goldstein, and I look forward to initiating interesting collaborations with other colleagues as well.  I am happy to be back in Israel as a PI and find that the research and collaboration is broader here.

Where do you hope your research will have the greatest impact? 

We hope our research will lead to the development of much-needed antifungal drugs.  Obviously, we are interested in everything fungi, but our lab is unique in that we don’t limit ourselves to just one environmental system or approach. Our scope goes beyond fungi and introduces ally sciences like ecology, medicine, economics, and geology.  We maintain active collaborations with hospitals in Israel and abroad on several clinical projects as well as applicative enterprises including the design of sprayable antifungals for application in agriculture, food industry and the clinic, including medical devices.  We even teamed up with a geologist to elucidate lichens physiology and environmental functions.

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