New Center Studies How Genes Shape Your Immune System

When it comes to getting sick, some people have the short end of the stick, catching nearly every cold and flu virus that comes their way. Others rarely get so much as a sniffle.  

What explains this disparity? Increasingly, scientists are discovering how a person’s genes shape the immune system’s ability to fight viruses, identifying certain genetic variations that make people more prone, or less, to viral illnesses.  

At Columbia, immunologist Dusan Bogunovic, PhD, is leading efforts to understand these genetic variations and use that information to help patients—both to treat rare immunological disorders and to treat and prevent common infections in the broader population.  

To aid in that endeavor, Bogunovic will this year launch the Columbia Center for Genetic Errors of Immunity, which will bring together doctors, nurses, and scientists working in the areas of genetics and immunology for collaborative research and training.  

“My dream is to create an environment where Columbia continues to be an unprecedented leader in this field, and we can get treatments to patients who need them,” says Bogunovic, who joined Columbia’s Department of Pediatrics in early 2024 as professor of pediatric immunology and vice chair for basic science research. “This is a very cross-disciplinary field, and everyone needs to be on the same page.” 

Over the past decade, as a professor at the Icahn School of Medicine at Mount Sinai, Bogunovic made inroads into identifying new genetic disorders that weaken people’s immune systems. In several cases, his findings directly led to ways of treating patients with existing drugs. That’s what he wants to see more of in the future.  

“Patients all over the world are referred to me with severe immunological disorders that doctors don’t know how to treat,” says Bogunovic. “I unfortunately can’t help all of them, but I hope we can put a system in place that connects them with appropriate researchers and clinical trials.” 

Driven by discovery 

Originally from Belgrade—part of the former Yugoslavia now known as Serbia—Bogunovic moved to the United States when he was 20, hoping to become a doctor. During his college years, he participated in an internship program at Memorial Sloan Kettering Cancer Center and fell in love with basic science.  

“It blew my mind how much exploration and discovery can be done at such a fundamental level,” he says. “And even today, that idea of pushing the mind to places it hasn’t gone before is still what keeps me excited about science.” 

As a graduate student, Bogunovic studied how the immune system responds to cancer, with some of his research setting the stage for clinical trials in the cancer immunotherapy field. When he joined the faculty at Mount Sinai, he was part of the Department of Microbiology, Department of Immunology, and Department of Pediatrics and began to study rare genetic defects that cause weakened immune systems and chronic inflammatory and autoimmune diseases. By studying the DNA from patients with mysterious, undiagnosed immune diseases, Bogunovic and his colleagues aimed to pinpoint exactly what causes those diseases.  

In 2020, one of his discoveries likely saved one young patient’s life. Bogunovic and colleagues discovered that a mutation in the USP18 gene—known to play a role in controlling JAK1-mediated inflammation—was responsible for a severe autoinflammatory disease in a young boy from Saudi Arabia. The disease is usually fatal, but after identifying the responsible gene, the boy’s doctors quickly gave the boy drugs that block JAK1. The boy went into remission and is just one example of the patients he has helped diagnose with genetic disorders.  

A personalized future 

At Columbia, Bogunovic sees a rich environment for collaboration between basic scientists and clinicians. His new Center for Genetic Errors of Immunity, he says, will facilitate these collaborations and help nurses and doctors learn how to identify rare immune diseases so they can refer patients to researchers like himself. Once those referrals are made, Bogunovic imagines clinical trials taking place, in which scientists and clinicians work together to study these rare diseases and how to treat them. 

Already, Bogunovic co-directs the New York Regional Inborn Errors of Immunity Resource Initiative League (NY ROYAL), a network of scientists and doctors from across New York institutions who meet regularly to discuss patients born with rare immune conditions and determine who can best spearhead the gene sequencing and workup for each patient.   

Through these kinds of networks—both within Columbia and around the world—Bogunovic thinks a picture will emerge over the coming years of how genes shape immunity and how that can change the practice of medicine.  

“The next generation of medicine involves personalizing your treatments to your unique genetics,” he says. “I imagine a future where patients learn they have a gene variation making them more likely to develop an autoimmune disease or more likely to get sick from a virus. Then we can have some preventive therapies that address that risk.”