Mary E. Brunkow’s path to international acclaim began with a fascination for genetics. In an interview she explained that as an undergraduate at the University of Washington she “always liked science in school” and that genetics captured her imagination because of its logical rules and its ability to explain visible traits. A hands-on research project in a fruit-fly genetics lab changed her trajectory from a pre-med track to a career in research. That curiosity eventually took her to Darwin Molecular, a Seattle biotechnology startup, where the Human Genome Project spurred new sequencing techniques.
Together with immunologist Fred Ramsdell, she set out to solve the mystery of a mutant mouse strain known as “scurfy.” These mice, described by Oak Ridge National Laboratory scientists in 1949, displayed scaly skin, enlarged lymph nodes, and early death. Only male mice were affected, hinting at a mutation on the X chromosome.
Sequencing the scurfy mice’s X chromosome was arduous; researchers narrowed the mutation to a region containing only 20 genes and painstakingly compared each gene in healthy and mutant mice. In the 20th gene they examined, Brunkow’s team found two extra DNA letters that disrupted a previously unknown gene they named FOXP3.
They showed that this mutation produced a non-functional protein and caused the mice’s fatal lymphoproliferative disorder. Subsequent work revealed that mutations in the human FOXP3 gene cause immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), linking the mouse findings to human disease.
FOXP3 belongs to a family of genes that encode proteins capable of binding DNA and regulating other genes. Brunkow, Ramsdell and collaborators published several seminal Nature Genetics papers in 2001 describing their discovery, demonstrating that FOXP3 is essential for the development of regulatory T cells — specialized immune cells that prevent our immune system from attacking the body.
On 6 October 2025, the Nobel Assembly at the Karolinska Institutet awarded Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi the Nobel Prize in Physiology or Medicine for “their discoveries concerning peripheral immune tolerance.”
The Nobel press release emphasized that the laureates identified the immune system’s “security guards,” regulatory T cells, which ensure that immune cells do not attack our own tissues. Brunkow and Ramsdell’s 2001 discovery explained why a specific mouse strain was vulnerable to autoimmune diseases: mutations in the newly named Foxp3 gene made the mice susceptible. Mutations in the human FOXP3 gene cause the severe IPEX syndrome, providing a genetic explanation for a previously mysterious disorder.
Their work launched the field of peripheral immune tolerance and has catalyzed research into therapies for autoimmune diseases, cancer and transplantation. Scientists now know that tumors often use regulatory T cells to evade the immune system; clinical trials are exploring ways to target these cells to improve organ transplantation and treat diseases like rheumatoid arthritis and inflammatory bowel disease.
Although the Nobel Prize recognized research done decades earlier, the honor thrust Brunkow into the public eye and highlighted the ongoing relevance of her discovery. In a January 2026 interview she noted that winning the prize brought “two months of pure chaos” as congratulations and media requests flooded in. Messages from people suffering from autoimmune diseases underscored the human impact of the research.
Brunkow is currently a senior program manager at the Institute for Systems Biology in Seattle, where she continues to support cutting-edge research. She is also a strong advocate for science communication. She believes good science communicators are essential to reach audiences beyond specialists and to inspire students by connecting classroom lessons to real-world applications.
Mary Brunkow’s journey from curious undergraduate to Nobel laureate illustrates the power of perseverance and fundamental research. Her discovery of the FOXP3 gene not only explained a fatal mouse mutation but also provided the molecular key to understanding regulatory T cells, reshaping immunology.
The resulting insights into peripheral immune tolerance are being translated into therapies for autoimmune diseases and cancer, offering hope to millions of patients. Brunkow’s commitment to science and her advocacy for education and communication make her a role model for aspiring scientists. As research builds on her work, her legacy will continue to influence medicine and immunology for decades to come.