When most people think about worms, fishing or composting come to mind. But Dr. Ransome van der Hoeven, an expert in microbiology and immunology, has made advances in our understanding of innate immune responses by studying the worm, C. elegans, a simple nematode.
For higher level organisms, like humans, it can be challenging to separate the immune response of non-immune system cells from the larger immune system, such as white blood cells. This challenge makes it harder for scientists to understand the mechanisms underlying innate immune responses of patients who are immunocompromised, whether from cancer treatment or autoimmune diseases, which it turns makes it harder to treat infections for immunocompromised patients.
Dr. van der Hoeven’s work focuses on mitis group streptococci, bacteria that normally live in the mouth and throat but can cause dangerous infections in vulnerable individuals. These bacteria produce hydrogen peroxide (H₂O₂), a compound that helps the bacteria defend against other microorganisms while also posing significant risks to human cells.
“Hydrogen peroxide production poses a dual threat,” Dr. van der Hoeven explains. “It enables harmful bacteria to thrive in competitive microbial environments like the oral cavity, but it also compromises host tissues, leading to inflammation and infection.”
By studying these factors in a simple organism without an adaptive immune system, Dr. van der Hoeven’s team hopes to gain insight into innate cellular defenses against these disease-causing bacteria.
More particularly, Dr. van der Hoeven and his research team are investigating how basic leucine zipper (bZip) transcription factors, which are a kind of protein that controls numerous cellular processes, can help cells detect and respond to bacterial H₂O₂.
“ZIP-2 and ZIP-10 appear to be key players in managing the oxidative stress caused by bacterial H₂O₂,” he says, “and our goal is to understand how these factors protect cells, and ultimately the body, from this type of bacterial threat.”
Insights gleaned from the C. elegans model also hold for human gingival fibroblasts, gum tissue cells directly involved in responding to oral bacterial infections.
“We are using a two-pronged approach to give a clearer picture of the cellular responses to bacterial H₂O₂,” he explains. “Incorporating human gingival fibroblasts allows us to validate findings from C. elegans and extend them to cells more directly involved in oral health.”
The implications of this research extend well beyond oral health, potentially leading to therapies that bolster immune defenses against bacterial infections, benefiting not only oral health but also individuals who have an elevated risk for infections due to weakened immune systems.
Dr. van der Hoeven is an associate professor in the Iowa Institute for Oral Health Research and the Department of Periodontics at the University of Iowa College of Dentistry. Since he joined the college in June 2024, he has appreciated the truly collaborative environment.
He is also deeply committed to mentoring the next generation of scientists and clinicians. He actively incorporates undergraduate students, dental students, and residents in his research, helping them gain firsthand experience in applying basic science to clinical care, as evidenced in his numerous publications with students on topics as diverse as dental education and alternative clinical uses of silver diamine fluoride.
“One of the most fulfilling parts of my role is mentoring those who are passionate about translating discoveries into improved patient care,” he says. “Seeing their growth and commitment to bridging science with practice is incredibly rewarding.”