The human immune system operates like a ten-armed soccer goalie defending against a constant onslaught of threats. When one health hazard is neutralized, another surfaces. Until 25 years ago, it was unclear how the body was able to determine friend from foe and what kept it from attacking healthy organs. That changed in 2001 when research by American scientists Mary E. Brunkow and Fred Ramsdell combined with discoveries by Japanese scientist Shimon Sakaguchi led to the identification of the cells that keep the immune system under control, earning the trio the 2025 Nobel Prize in Physiology or Medicine.

The reality hit home when her husband opened the door in the early hours and was greeted by a photographer who delivered the news. 

News of the award took Brunkow completely by surprise, she says to NLS, especially since she silenced her phone after several early morning calls from Sweden that she thought were spam. The reality hit home when her husband opened the door in the early hours and was greeted by a photographer who delivered the news. 

Mary Brunkow at a press conference held at ISB on October 7, 2025. Photo: Alex Garland for ISB

Groundbreaking work

Mary Brunkow, now a senior program manager at the Institute for Systems Biology (ISB) in Seattle, Washington, US, did her groundbreaking work at Darwin Molecular, which became Celltech in 1998. She was a scientist in the molecular biology/genomics group and Fred Ramsdell headed up the company’s immunology section. Their two labs were next to each other. “There was constant interaction between our two groups,” Brunkow says. “Fred has remained a good friend since those days of working together.”

During their studies, Brunkow and Ramsdell discovered that a certain strain of mice who were affected by profound autoimmune disease carried a mutation in a gene that is now known as FoxP3. They also found that an autoimmune disease in humans was caused by mutations in the human equivalent of FoxP3.

Sakaguchi later determined that the FoxP3 gene regulates the development of cells he had identified in 1995. Now called regulatory T cells (Tregs), they are responsible for monitoring other immune cells and ensuring that our immune system tolerates our own tissue. Known as peripheral immune tolerance, understanding how the immune system sorts out threats has led to new treatments, for example in cancer and autoimmune diseases.

My strengths and contribution to the work that is being honored is really in the areas of genetics, genomics, and molecular biology. I would never claim to be an immunologist!

While Brunkow has not studied peripheral immune tolerance since Celltech closed in 2003-2004, she has followed developments in the field, and the Nobel Prize has prompted her to reflect on the discovery and its clinical applications.

“I have become more deeply familiar with just how broad an impact our work has had, with very gratifying major advances made in human treatments based on regulatory T cell biology,” she says. “The therapeutic areas that have seen the most advancements include autoimmune disease, organ transplantation, and cancer. My strengths and contribution to the work that is being honored is really in the areas of genetics, genomics, and molecular biology. I would never claim to be an immunologist!”

End goal of translatable discoveries

Mary Brunkow started college with the intention to study medicine, majoring in cell and molecular biology, but her focus changed after she took a genetics class in her senior year with a dynamic professor and participated in a student research project in his lab.

“I was quickly taken in by the magic of an environment with such intense focus and sense of excitement,” Brunkow says. “It didn’t take long for me to start making plans to pursue graduate school rather than med school.”

I was able to pursue early-stage research that was as exciting as anything that I thought I might be doing in academia, but within an environment where everyone shared the common goal of ultimate translation into the clinic.

Since then her career has shifted between industry and academia, but always with a focus on work that could improve patients’ lives. “When the time came to start thinking about the next step after my postdoc I felt that I would be more satisfied in an environment where my contributions would be directly connected to treating human diseases,” Brunkow explains.

Mary E. Brunkow. Photo: Alex Garland for ISB

The chance to work at the gene discovery-based biotech start-up Darwin Molecular seemed to be the perfect answer.

“I was able to pursue early-stage research that was as exciting as anything that I thought I might be doing in academia, but within an environment where everyone shared the common goal of ultimate translation into the clinic.”

Since joining ISB in 2009, Brunkow’s work is again more academically focused, but her motivation remains the same. “Throughout my career, whether in academia or industry, exploring new areas primarily aimed at generating translatable discoveries, is what keeps me interested and engaged,” she says.

Science in the US

Outside of work, Brunkow’s passions include walking, hiking, biking, traveling, baking, gardening, films, concerts, and spending time with her husband, twin daughters, and dog.

Many scientists have been hit in a more direct way and that has resulted in having to close research programs and even entire labs.

The current scientific research climate in the US is worrisome, Brunkow notes, because of reductions in federal grants and uncertainty about the future of research.

“This climate shows the effects of recent drastic and unexpected cuts to federal funding that are often not accompanied by thoughtful rationale,” she says. “Most scientists are feeling anxious due to the uncertainty, and this undoubtedly leads to decreased productivity. Many scientists have been hit in a more direct way and that has resulted in having to close research programs and even entire labs.”

If the situation continues, the US risks losing its place as a global research leader.

“I worry that many good scientists at all different career levels will find it necessary to leave the US to find their most fulfilling career track,” Brunkow says. “If that happens to a significant degree, it will take a very long time for US science to recover.”

Don’t be afraid to follow a new trajectory

Young people interested in science shouldn’t be discouraged, though, and should pursue their passions, she adds. “Follow your heart, or gut, or wherever you feel that spark of interest and really dive deeply into something that excites you,” Brunkow continues.

Bear in mind that there are many ways to work in science.

“Bear in mind that there are many ways to work in science – keep your mind open to all different kinds of opportunities that present themselves and don’t be afraid to follow a new trajectory. Also, remember that big advances don’t usually happen in isolation, so be a good team player – it’s actually more fun that way – and embrace the give-and-take of sharing ideas, successes, and setbacks.”

Mary E. Brunkow
  • Age: 64
  • Born: Portland, OR, USA
  • Nationality: American
  • Current role: Senior program manager at the Institute for Systems Biology (ISB) in Seattle, Washington
  • Education: B.S., University of Washington, Ph.D., Princeton University
  • Personal: Married, has twin 19-year-old daughters and a dog