Most people do not consider fungal infections a serious medical threat. In fact, for a healthy person, the immune system handles fungal invaders so efficiently that most encounters do not develop into illness. But for patients with compromised or defective immune systems, such as those with diabetes, liver disease, or those recovering from an organ transplant, the story is very different. For these patients, a fungal infection can become life-threatening, and doctors currently have very limited tools to help. Dr. Alex Hopke, an assistant professor in the Department of Biomedical Sciences at the Quillen College of Medicine, is working to change that.
Dr. Hopke’s path to ETSU began at the University of Maine, where he earned his bachelor’s and doctoral degrees in microbiology. During his Ph.D. work, he first became fascinated with neutrophils, the white blood cells that serve as the immune system’s front-line soldiers, and how they interact with fungal pathogens. After completing his Ph.D., he spent seven years at Massachusetts General Hospital in Boston as a postdoctoral fellow, where his research became more specific: neutrophil swarming.
To understand swarming, think of a neutrophil as a Pac-Man. In most cases, when a neutrophil encounters a foreign invader, it simply engulfs and destroys it. But some fungal pathogens, like Candida albicans, can shift from a small, round yeast form into long, branching structures called hyphae. These hyphae are too large for a single neutrophil to swallow. That is where swarming comes in. When one neutrophil cannot finish the job alone, it sends out chemical signals that call in reinforcements from a sizable distance. Within minutes, dozens of neutrophils converge on the same target in a coordinated attack.
“You can think of them almost as a pack of piranhas all coming and concentrating on getting rid of this pathogen,” Dr. Hopke said.
The challenge for researchers has long been that studying this behavior in a meaningful way was technically difficult. In response, Dr. Hopke developed a specialized microfluidic device, essentially a miniaturized lab-on-a-glass slide that lets him observe swarming in real time using a microscope. The device uses a printer to create arrays of 100 microscale spots, each of which can then be coated in fungal material. Each spot triggers a swarm response, allowing researchers to observe up to 64 individual swarms simultaneously across different experimental conditions.
Since bringing the device to ETSU, Dr. Hopke has adapted it to work with live hyphae rather than yeast clusters, which more accurately reflects how fungal infections actually behave in the body. The device also enables his team to draw blood directly from patients, isolate the neutrophils, and test them immediately, producing results grounded in human biology rather than animal models.
At ETSU, Dr. Hopke has focused his patient research on people with poorly controlled diabetes, defined in his work as those with an A1C above 10 percent. These patients are particularly vulnerable to fungal infections, and the lab has found that their neutrophils show clear deficits in swarming ability. When his team treated the impaired neutrophils with cytokines, the cells’ swarming function could be largely restored.
“It usually almost entirely restores their neutrophil function,” Dr. Hopke said.
The goal now is to understand exactly how these cytokines fix those cells so that a more targeted therapy can be developed, one that could one day help shield the patients most at risk from life-threatening fungal infections.
The broader vision behind Dr. Hopke’s work is to turn this device into a clinical tool for measuring immune function in vulnerable patients. By watching how a patient’s neutrophils swarm, or fail to swarm, doctors could gain a precise picture of where their defenses are breaking down and test potential interventions before committing to a treatment. The research remains in the laboratory phase, but the potential applications could aid in oncology, transplant medicine, and infectious disease.
For Dr. Hopke, the appeal of this research has always been rooted in what you can see. His lab produces video footage of the entire swarming process, from the first neutrophil encountering the hyphae to the wave of reinforcements rushing in from the edges of the frame. The footage is striking, less like what most people imagine science to look like and more like watching a coordinated military operation unfold at a microscopic scale. It is a reminder that even within a single drop of blood, the body is already fighting wars that most people never know are happening.
