A career in research that has made a difference for patients and public health
When St. Olaf College alumnus Paul McCray ’76 first got involved with cystic fibrosis (CF) research as a pediatric pulmonology fellow with University of Iowa Professor of Internal Medicine Mike Welsh, the average life expectancy for patients with this congenital lung disease was in the 20s. Patients were cared for by pediatricians their whole lives, which were spent in and out of hospitals with recurring lung infections. The disease was not well understood.
“People just didn’t live long enough for adult doctors to become well-trained in their care,” McCray says. “But here was [Welsh] over in internal medicine doing research on cystic fibrosis, and I was fascinated by that idea.”
That was the beginning of a productive research relationship of nearly 40 years that continues to this day. At the start of McCray’s tenure as an assistant professor at the University of Iowa in 1991, the field was experiencing a research boom in response to the recent discovery of the genetic cause that underlies CF pathology. He began to work on possible gene therapies using viral vectors to deliver working copies of the gene to a patient’s cells.
“That work has continued to the present day,” McCray says. “We’re still tweaking those vectors to make them more efficient. As time has gone on, we’ve also begun to think about how these tools could be applied to other disease states that involve the cells that line the respiratory tract.”
“The projects I’ve worked on have involved many iterations of trial and error. But one of the reasons I’ve stuck with research is that it’s ever-changing. You can’t investigate the same thing forever; there’s always a need to learn new things.”
— Paul McCray ’76
McCray also performed fundamental research that furthered medical understanding of SARS, MERS, and COVID-19. These collaborations with University of Iowa Professor of Microbiology and Immunology Stanley Perlman began in the late 1990s, when they were exploring whether coronaviruses could be used as a gene therapy vector.
“That didn’t pan out, but we learned a lot about coronaviruses,” McCray says. “Then, when the SARS pandemic happened, Stan and I started talking about doing some work together again. Over time this collaboration included studies of MERS, and then it went into overdrive with COVID.”
A mouse model of coronavirus infection that McCray had previously developed during their work with SARS — often referred to as the K18 mouse — became one of the most scientifically useful vehicles for studying COVID-19 and testing vaccines and treatments. His knowledge of host defenses and virus entry mechanisms have also been employed to advance basic science on airway epithelia, especially a class of antimicrobial peptides called defensins.
“These are natural antibiotics that the cells that line the lungs produce and secrete into the liquid that bathes your airways,” McCray explains. “We got very interested in whether, in cystic fibrosis, part of the reason that people get lung infections is because these naturally occurring antibiotic substances don’t work as well.”
McCray discovered and characterized the human and mouse beta-defensin gene clusters that protect the lung, a body of work that has formed a foundation for better understanding innate immunity in the lungs and in diseases of the kidney, gastrointestinal tract, and skin.
A first-generation college student who majored in biology at St. Olaf and now serves as the Roy J. Carver Chair in Pulmonary Research, McCray has been a role model and mentor to graduate students, postdoctoral fellows, pediatrics trainees, and junior faculty at Iowa.
In honor of this work and his exceptional accomplishments, he received the 2024 Distinguished Alumni Award for Achievement from the University of Iowa Carver College of Medicine this fall. He was also awarded the 2024 Trailblazer Award from Emily’s Encourage, a nonprofit foundation dedicated to accelerating research for new treatments and a cure for CF. This award celebrates leaders who demonstrate innovation, courage, and tenacity in advancing life-saving research for the CF community.
The wisdom that McCray imbues is grounded in the ebbs and flows he has weathered as an experienced physician-scientist.
“There are inherent frustrations with pursuing research as a career path. You don’t get magic overnight,” McCray says. “The projects I’ve worked on have involved many iterations of trial and error. But one of the reasons I’ve stuck with research is that it’s ever-changing. You can’t investigate the same thing forever; there’s always a need to learn new things.”
That passion for research began with the mentorship he received at St. Olaf, McCray notes.
“My love of biology and first research experiments grew during my time at St. Olaf,” he says. “Classes with Professor Eugene Bakko were my first real exposure to hypothesis testing in research and had a lasting influence on my love of biology and research.”