Mary Brunkow PhD is Senior Program Manager at the Institute for Systems Biology in Seattle in the US. She was one of three co-winners of the 2025 Nobel Prize in Physiology or Medicine for the discovery of regulatory T cells (Tregs). She shares her career highlights and some word of wisdom with Diana Turner. 

DT: What do you do and what are you working on at the moment?

 

MB: For the past 16 years I have been working at the Institute for Systems Biology in Seattle as a Senior Program Manager, primarily supporting Dr Lee Hood’s laboratory. The team has been and is involved in systems biology analysis in a variety of health-related areas, including Huntington’s disease, Alzheimer’s disease, sepsis, Lyme disease, multiple sclerosis, cancer survival, longevity, ageing, and frailty. Because we do not interface with patients directly all our studies are done in collaboration with clinical researchers and so much of my job involves supporting those collaborations, as well as managing budgets and grants, helping to write up results, etc. Although my official role generally keeps me watching over projects from the 30,000-foot level, I am free to contribute intellectually to any of the projects to whatever degree I am able. Another gratifying part of my job was supporting ISB’s Innovator Award Program, which solicited novel, high-risk project proposals from young ISB researchers and provided funding for 12-18 months after competitive review. Many of these relatively short pilot projects went on to secure additional Federal funding and/or commercialisation opportunities. 

DT: What’s been the highlight of your career?

 

MB: Well, winning the Nobel Prize is pretty hard to beat and I don’t imagine there’s anything else that could happen in my career in future that will top it! 

But two major highlights from my career as a bench scientist at the small biotech company Darwin Molecular (later part of Celltech): 

  • Discovery of the FOXP3 gene (which of course is what is being recognised by the Nobel Prize) and knowing how this work launched an important new area of inquiry in immunology that has led to the development of therapies for several human disease conditions. 
  • Discovery of the SOST gene, which when mutated causes sclerosteosis, a condition of marked bone overgrowth. Mimicking the effect of the mutation via a blocking antibody led to the development of a drug to treat bone loss, such as post-menopausal osteoporosis. The drug (romosozumab/Evenity) was co-developed by Celltech and Amgen and is now on the market. 

DT: What drug discovery breakthrough has been most impactful to your research?

 

MB: Approval of the anti-SOST antibody for treatment of osteoporosis was an exciting and an  important validation of the “drug surrogate model” that underpinned Darwin Molecular’s approach to drug target discovery: 1) identify a phenotype with characteristics that, under some conditions, would be clinically advantageous; 2) use molecular genetics and genomics tools to identify the affected gene; and 3) develop a drug with activity that mimics the original phenotype in a clinically relevant way. The discovery of FOXP3 was also the result of a similar approach in autoimmunity. In this case, however, the FOXP3 gene product Scurfin turned out not to be a druggable target itself (it is a DNA-binding protein), but it did provide researchers with a hook into the previously inaccessible realm of the immune system that is controlled by regulatory T cells. 

DT: What has been the best piece of career-related advice you have received?

 

MB: Don’t discount serendipity as a legitimate phenomenon that can lead to positive career advancement. 

DT: What advice would you offer to someone hoping to follow in your footsteps?

 

MB: Follow your heart when a particular area of research really grabs your attention. Work hard to carve out your special niche. It’s almost always more productive, and enjoyable, to work collaboratively so embrace the give-and-take of sharing ideas and successes, as well as setbacks. Most big advances in science do not happen in isolation. Also keep an open mind to alternate career trajectories; there is not just one track to follow to be a successful scientist. As one of my mentors pointed out, serendipity sometimes opens new doors but you have to keep your eyes open to notice! Keep a healthy balance between work and your other life priorities.