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Controlling innate immunity, from the bench to the bedside

Prof. Aaron Esser-Kahn is working to understand innate immunity to make better vaccines while lending his expertise to quantum research

In high school, Prof. Aaron Esser-Kahn was drawn to stories of people whose research caused a fundamental shift in the world. In one assignment, he listed Fritz Haber—who invented the process to synthesize ammonia from nitrogen—as the kind of scientist he wanted to be. “I’ve always been very motivated to build tools that could change the world in new and interesting ways,” he said. 

An undergraduate degree from Caltech and a PhD in chemistry from University of California, Berkeley set him on a path to become an academic researcher. But he found himself turning to biology—specifically, the complicated network of the immune system.

“I saw there could be so much more done to improve the immune system,” he said. “ Ultimately, I wanted to take my ideas and turn them into therapies.”

Fifteen years later, the University of Chicago Pritzker School of Molecular Engineering (UChicago PME) professor is on the path to commercialize his research in innate immunity that makes vaccines safer and more effective. His work, though, could have far-reaching impact beyond vaccines. Many diseases, including cancer, involve dysregulation of the immune system.

“We are still really at the beginning of learning what we can do with the innate immune system and how it can be used as a part of our overall health,” he said.

Learning to control the innate immune system

Early in his career, Esser-Kahn chose to focus on immunoengineering and materials research. But as a professor at University of California, Irvine, “I was the only person working in those areas.” 

When he arrived at UChicago PME in 2017, “I was now part of a bigger team that could work together and build new things,” he said. “It’s a place that is well-suited to move ideas out of the laboratory and into the world.”

In his lab, Esser-Kahn looks for ways to modify the body’s innate immune response in a controlled fashion. That’s important, since many ways we harness the power of the immune system, including vaccines, don’t target innate immune cells. Instead, they target the adaptive immune system, which can be trained to identify and fight pathogens. 

Innate immune cells—the first responders to pathogens—don’t have that same long-term memory. Esser-Kahn’s breakthrough was to find new small molecule candidates that can reprogram these first-responder innate immune cells to both better fight off common viruses and to potentially protect against new viruses for which there are no vaccines. 

These small molecules—drugs that can easily enter cells—would allow scientists to be more targeted and specific with their immune training, making vaccines safer and more effective. 

The work builds on years of Esser-Kahn’s research into first-responder cells and in adjuvants, ingredients that help boost the immune response in vaccines. With a partnership with Inimmune Inc., Esser-Kahn’s lab is working to create a flu vaccine with adjuvants to make it safer for more vulnerable populations. 

Esser-Kahn and his lab are testing one commercially viable small molecule in larger animal models, the next step on the path taking his innate immunity research to clinical trials in humans. 

“This research is all part of a larger story that are building toward being able to change the conversation around vaccines,” he said. “There are risks and benefits with vaccines, and we are trying to minimize risks while increasing the benefits.”

Going beyond vaccines

At UChicago PME, Esser-Kahn has even lent his expertise to quantum engineering. This year, he has worked with quantum researchers Prof. Peter Maurer and Prof. David Awschalom on projects to develop a biological qubit and to create a new quantum biosensor.

“When I got to UChicago PME and started talking to faculty who working in quantum measurement, it became clear that they had much better ways of measuring things than biologists were currently using,” he said. “So you can watch other people build a future, or you can grab a shovel and help out.”

Esser-Kahn brought the biological expertise, both in knowledge of proteins but also in what biologists might want out of a quantum measurement tool. “This work is the sort of thing that can’t be done by one person in one field. It can only be done if you talk to people across departments, in a place that allows students to find new ideas. That’s my favorite kind of science, and UChicago PME provides the space for doing work like this.”

Esser-Kahn is also working with Maurer on research funded by the Chan Zuckerberg Biohub Chicago to better understand and correct dysregulation of the innate immune system.

“A lot of the damage from a disease really comes from the dysregulation of the innate immune system, rather than the dysfunction of your body itself,” he said. “So we are trying to understand how to get the innate immune system to do what it ought to do and how to maintain itself, which is a really exciting challenge.”