A new study offers a glimpse of why that is — and how we might finally begin to predict who will benefit from particular microbiome-based interventions before trying them.

In work published in PLOS Biology, researchers from ISB’s Gibbons Lab used computer models of gut metabolism to forecast whether introduced probiotic bacteria would successfully establish themselves in an individual’s gut microbiome — and how dietary prebiotics might influence the production of health-promoting molecules in the gut.

“Our models don’t just look at which microbes are present,” said Dr. Nick Quinn-Bohmann, lead author of the study. “They simulate how microbial communities interact with one another and with what a person eats.”

The team tested their approach across several different groups, including people with type 2 diabetes, healthy volunteers who participated in a phase I safety trial of a probiotic cocktail developed to prevent recurrent Clostridioides difficile infections, and a large cohort of generally healthy participants who increased their dietary fiber intake.

Across these diverse settings, the models were able to predict, with notable accuracy, whether specific probiotic strains would successfully colonize in a given person’s gut and how gut chemistry would shift in response to probiotic and dietary interventions.

One striking finding was that probiotic success wasn’t random. Whether a strain took hold depended heavily on the existing microbial ecosystem inside each person — and in some cases, the growth of a given probiotic was associated with clinical markers, such as lower blood glucose levels.

“In other words, the gut environment itself appears to set the rules for whether new microbes can move in and meaningfully change what’s happening metabolically,” said ISB Associate Professor Dr. Sean Gibbons, senior author of the paper.

Beyond probiotics, the models also captured how changes in fiber intake shaped gut metabolites and cardiometabolic markers in a large population. That suggests this kind of modeling could eventually inform more personalized dietary guidance, moving beyond one-size-fits-all nutrition advice.

Taken together, the work points toward a future in which microbiome-based therapies — probiotics, prebiotics, and diet — are chosen based on an individual’s biological context rather than guesswork.

“By combining longitudinal data, mechanistic modeling, and increasingly rich biosensing tools, we are beginning to sketch out what truly personalized microbiome medicine might look like,” Gibbons said. “Not just trying things and hoping they stick, but knowing, ahead of time, what’s likely to take.”

The post Will It Stick? How to Tell Whether Probiotics and Prebiotics Will ‘Take’ appeared first on Institute for Systems Biology (ISB).

“Academy Fellows are leaders in their field whose work influences the direction of scientific discovery and its role in society,” said Vanessa Sperandio, Ph.D., chair of the Academy Governors. “Election to the Academy is a significant professional milestone, and I am delighted to welcome Nitin Baliga as a member of the 2026 cohort.”

“Microbiology sits at the intersection of fundamental discovery and urgent global health and environmental sustainability needs. I’m grateful for the recognition, and more importantly, to be part of an interdisciplinary community working to bridge that gap,” Baliga said. 

The 2026 Fellowship Class brings a wealth of knowledge across the microbial sciences, with representation from around the globe. The 63 fellows hail from 14 countries, including Australia, Belgium, Canada, China (mainland), the Czech Republic, Denmark, Israel, the Netherlands, South Africa, Spain, Sweden, Switzerland, the United Kingdom, and the United States.

“On behalf of ISB, I’m delighted to congratulate Nitin on this outstanding honor. His election to the American Academy of Microbiology is a powerful recognition of the scientific rigor and impact of his work in microbiology and systems biology,” said ISB President and Professor Dr. Jim Heath. “Nitin brings a rare combination of deep technical expertise, intellectual curiosity, and leadership — he’s the kind of scientist who not only pushes the field forward, but builds the teams and culture that make sustained discovery possible. He is also a devoted science educator, having founded and led the ISB Systems Education Experiences program for the past 25 years.”

Learn about the 2026 Fellowship Class.

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About ISB

The Institute for Systems Biology (ISB) is a collaborative, cross-disciplinary, non-profit biomedical research organization based in Seattle. We focus on some of the most pressing issues in human health, including aging, brain health, cancer, chronic illness, infectious disease, and more. Our science is translational, and we champion sound scientific research that results in real-world clinical impacts. ISB is an affiliate of Providence, one of the largest not-for-profit healthcare systems in the United States. Follow us online at isbscience.org, and on YouTube, Facebook, LinkedIn, X, Bluesky, and Instagram.

About ASM 

The American Society for Microbiology is one of the largest professional societies dedicated to the life sciences and is composed of over 38,000 scientists and health practitioners. ASM’s mission is to promote and advance the microbial sciences.  ASM advances the microbial sciences through conferences, publications, certifications, educational opportunities and advocacy efforts. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry, and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to all audiences.

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Postdoctoral fellows are the lifeblood of research institutions, yet their contributions are often underrecognized. At the Institute for Systems Biology (ISB), postdocs enter the scientific workforce with passion, vision, and advanced training – bringing the fresh ideas that fuel discovery.

“Postdocs are the pulse of ISB,” said ISB Director, Senior Vice President, and Professor Dr. Nitin Baliga. “The innovation that happens here is driven, in large part, by the ideas that postdocs bring when they work with professors at ISB.”

In 2025, ISB Board Member Douglas Howe pledged a generous $100,000 matching gift to support postdoc fellowships — and thanks to the collective generosity of donors and board members, the match was met. 

“ISB has a long history of welcoming and mentoring postdocs and giving them the tools to build successful, independent careers,” Howe said. “I’m proud to join my peers in supporting opportunities that help the next generation of scientists thrive — and to help open doors for future postdocs to make their mark.”

A postdoc’s journey at ISB goes beyond research – it prepares them to solve real-world problems that require interdisciplinary skills and collaboration across labs.

“At graduate school, you learn how to do research. But going from that skillset to becoming an independent investigator, whether in academia or industry, is a rigorous journey,” Baliga said. “At ISB, postdocs learn not just how to do research, but how to establish their own research programs.”

Learn more about ISB’s Postdoctoral Fellow Program by watching the video above, and hear from three current ISB postdocs in the short videos below.

The post Behind the Breakthroughs: ISB’s Postdoctoral Fellows in Focus appeared first on Institute for Systems Biology (ISB).

Published in the Annual Review of Pharmacology and Toxicology, the authors describe a shift underway in precision medicine: moving from static, single biomarkers toward dynamic, systems-level signals that are tracked over time within individuals. By combining longitudinal multiomics data, wearable and digital health measurements, and AI-driven analytics, the authors argue that researchers are getting closer to mapping personal “health trajectories” and spotting subtle deviations that may mark the beginning of disease.

“Most diseases don’t begin with a single broken marker. They begin as small, coordinated shifts across biological systems. What’s new is that longitudinal data and AI now let us see those shifts early, in the context of each person’s own baseline, rather than waiting for disease to declare itself,” said Dr. Noa Rappaport, an ISB scientist and the review’s lead author.

A central theme of the review is the importance of context. Traditional screening tools often struggle in low-prevalence populations, where even highly specific tests can generate large numbers of false positives. The authors argue that systems approaches — which integrate multiple biological signals and incorporate personalized baselines — could improve performance by separating normal variation from meaningful change.

The review also highlights emerging AI capabilities that can accelerate clinical translation. These include machine learning models that integrate large-scale datasets, knowledge graphs that connect patient data to biomedical literature, and “digital twin” approaches that use computational models to simulate how an individual’s biology may respond to interventions.

“Current medicine is focused on disease care. Data-driven individual health allows one to optimize their wellness and potentially prevent transitions to chronic diseases such as diabetes, cardiac disease, and Alzheimer’s disease. Data-driven health enables one to extend their healthspan, the number of years you are healthy, potentially into the 90s or beyond,” said Dr. Leroy Hood, ISB co-founder and an author on the paper. 

The authors draw on pioneering longitudinal studies from ISB — including large-scale scientific wellness efforts — to illustrate the potential of deep phenotyping and network-based analyses to detect early molecular signals associated with disease. 

They also note key challenges ahead, including data standardization, clinical validation, privacy and security, bias and equity, and regulatory considerations for AI-enabled tools.

Ultimately, the review positions AI-driven systems biology as a foundation for next-generation precision health — one that supports earlier intervention, more personalized treatment, and the possibility of preventing disease progression before it becomes clinically apparent.

“Over the next 10 years, we will gradually see our current disease-focused healthcare replaced with a healthcare focused on wellness and prevention,” said Hood.

Read the paper: Early Detection of Wellness-to-Disease Transitions in the AI Era: Implications for Pharmacology and Toxicology, 2026, Annual Review of Pharmacology and Toxicology

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A defining moment came with the awarding of the Nobel Prize in Physiology or Medicine to ISB’s Dr. Mary Brunkow, honoring foundational discoveries in immune tolerance made earlier in her career that continue to influence modern medicine. Alongside this historic recognition, ISB researchers advanced new insights across cancer biology, immunology, microbiome science, artificial intelligence, and translational informatics — extending a 25-year legacy of innovation rooted in systems thinking.

Beyond scientific achievement, 2025 reflected ISB’s commitment to convening global conversations, building community, and investing in the next generation of scientific leaders. Through public events, open research platforms, education initiatives, and partnerships around the world, ISB celebrated both progress and purpose — honoring those who have shaped our past while laying the groundwork for discoveries yet to come.

Nobel Prize

Mary E. Brunkow Awarded the 2025 Nobel Prize in Physiology or Medicine

In one of the most historic moments for ISB, Dr. Mary Brunkow was awarded the Nobel Prize in Physiology or Medicine for her groundbreaking discoveries in immune tolerance and the central role of regulatory T cells (Tregs). Her pioneering work — including identifying the FOXP3 gene as the master regulator of Tregs — reshaped modern immunology and opened new pathways for treating autoimmune disease, transplantation, cancer, and beyond. The Nobel Assembly honored Brunkow, Fred Ramsdell, and Shimon Sakaguchi for discoveries that continue to influence global health and biomedical research. Read More →

Scientific Breakthroughs

Disarming a Hidden Killer: Predicting — and Preventing — C. diff Before It Strikes

Researchers at ISB have developed a personalized modeling framework that can predict whether C. diff is likely to colonize an individual’s gut — a critical step in preventing severe, sometimes life-threatening infections. The study, published in Cell Systems, also shows how specific probiotic therapies might block or reverse colonization. The work offers a powerful new path toward anticipating infection before symptoms ever appear. Read More →

Hidden Rules of Immune Response 

ISB researchers uncovered key “rule sets” that govern how T cells recognize and respond to pathogens. Using APMAT — a computational–experimental framework — the team could predict which T cells would expand, persist, or fade during infection. The findings open new avenues for improving vaccines and immunotherapies. Read More →

Melanoma’s Rapid Treatment Evasion

A joint ISB–MIT study revealed that melanoma cells begin adapting to targeted therapy within hours — long before genetic resistance kicks in. The research identifies an early, reversible state that enables cancer cells to survive BRAF inhibitors and proposes a combination strategy to block it. The findings point toward more durable treatments for melanoma. Read More →

MEDI: Detecting Diet From Stool DNA

ISB scientists introduced MEDI, a novel method that uses stool metagenomic data to reconstruct a person’s diet from food-derived DNA. This objective, data-driven approach could complement or replace traditional food diaries, which often rely on self-report and suffer from recall bias. MEDI opens new opportunities for nutritional research and microbiome–diet studies. Read More →

A New Way to Measure Gut Bacterial Biomass

ISB researchers developed a simple, cost-effective method to estimate absolute bacterial biomass in stool samples using the ratio of bacterial-to-host DNA reads. Published in mSystems, the technique allows scientists to calculate biomass directly from standard metagenomic data — no specialized equipment or complex workflows required. This approach could accelerate microbiome research across fields. Read More →

Biomedical Data Translator Release

The Biomedical Data Translator Consortium released a powerful, open-source knowledge graph platform that integrates diverse biomedical datasets into a unified system. The tool enables researchers and clinicians to explore connections across genomics, pharmacology, clinical data, and more — without specialized computational expertise. Published in Clinical and Translational Science, the release marks a major advance in translational informatics. Read More →

Rethinking the Genetic Paradigm of Cancer

In a provocative PLOS Biology essay, ISB Professor Sui Huang argues that cancer cannot be understood solely through genetics — and that cellular “states” and network dynamics play a critical role in tumor behavior. The piece challenges long-standing assumptions and calls for a more holistic, systems-level approach to cancer biology. It adds fresh perspective to ongoing debates about precision oncology. Read More →

Microbial Partnerships and Ecosystem Vulnerability

ISB researchers discovered that denitrifying microbial communities — central to global nitrogen cycling — become surprisingly fragile in contaminated environments. When nitrate levels exceed certain thresholds, cooperative processes break down and produce harmful byproducts like nitrous oxide. The findings illuminate how human activity can destabilize key microbial ecosystems. Read More →

mmSYGNAL: Transforming Myeloma Risk Prediction

A team led by ISB researchers unveiled mmSYGNAL, a machine-learning model that predicts risk in multiple myeloma by analyzing the gene-regulatory networks driving each patient’s disease. Published in the British Journal of Cancer, the tool provides deeper insights than traditional mutation-based classifications. It may help clinicians tailor therapies more precisely. Read More →

Awards and Honors

Dr. Lee Hood Receives Inaugural Michael Sela Prize from Weizmann Institute of Science

ISB Co-founder and Professor Dr. Lee Hood was named an inaugural recipient of the Michael Sela Prize in Biomedical Sciences from the Weizmann Institute of Science, recognizing transformative contributions to modern biomedicine. Hood shares the international honor with Francis S. Collins and Eric S. Lander for pioneering work that reshaped genomic science and human health. Read More →

ISB Named Winner of 2025 Amazon Web Services Imagine Grant for Nonprofits  

ISB has won a 2025 AWS Imagine Grant to advance Tarpon, a generative AI platform that generates digital fingerprints of T cell receptors. By linking immune signatures to genomic and clinical data, Tarpon enables rapid discovery and the design of targeted therapies. Read More →

Events & Public Engagement

Eric Topol and Lee Hood: Two Luminaries on Longevity and Prevention

Renowned physician-scientist Dr. Eric Topol joined ISB Co-founder Dr. Lee Hood for a virtual discussion on the science of longevity, prevention, and healthspan, inspired by Topol’s book Super Agers. The conversation explored how genomics, AI, and lifestyle science are converging to extend years lived in good health, not just lifespan. Read More →

From Genesis to Reality: Decoding the AI Revolution

Former Microsoft Chief Research and Strategy Officer Craig Mundie joined ISB President Dr. Jim Heath for a public conversation at Town Hall Seattle exploring the rapidly evolving landscape of artificial intelligence and its societal implications. Co-presented by ISB and Town Hall, the event drew on Mundie’s new book, Genesis: Artificial Intelligence, Hope, and the Human Spirit, co-authored with Eric Schmidt and the late Henry Kissinger. Read More →

Microbial Metabolites and Human Health: 2025 Virtual Microbiome Symposium

ISB convened leading researchers from across the U.S. and abroad for its 2025 Virtual Microbiome Symposium, focused on how microbial metabolites shape immune, neural, and systemic health. The free, global event drew more than 1,000 registrants from over 70 countries and featured talks and panel discussions exploring emerging mechanisms, translational challenges, and the future of microbiome-informed medicine. Read More →

What We’re Learning About Long COVID

At a November 2025 virtual town hall, leaders from the Pacific Northwest RECOVER hub shared emerging insights from the RECOVER 1.0 study and discussed where the science is headed next. ISB President Dr. Jim Heath joined Dr. Helen Chu and Dr. Jason Goldman to highlight early findings and preview upcoming clinical trials aimed at translating biology into improved care. Read More →

RECOVER 2.0: New Insights and Next Steps in Long COVID Research

In July 2025, ISB convened its second virtual RECOVER town hall of 2025 to outline the next phase of the study, known as RECOVER 2.0. Led by Dr. Jason Goldman, the session detailed plans to follow more than 5,000 participants nationwide to better define long-term disease trajectories and explore links to neurocognitive, cardiopulmonary, and autoimmune conditions. Read More →

RECOVER Study on Long COVID: Virtual Town Hall

ISB hosted a virtual town hall in January 2025 to share updates from the NIH-funded RECOVER study, a national effort to understand and address Long COVID. ISB President Dr. Jim Heath, who leads the Pacific Northwest RECOVER hub, was joined by clinical leaders Dr. Helen Chu (UW Medicine), Dr. Jason Goldman (Swedish/Providence), and study coordinators to discuss progress, participation, and next steps. Read More →

How Generative AI Is Helping Decode the Human Immune System

In an ISB Research Roundtable, Dr. Jim Heath introduced Tarpon, a generative AI model developed with researcher Daniel Chen to uncover fundamental principles governing human immune development. Trained on more than one million T cell receptor sequences, the model offers new insights into immune function across aging, cancer, and infectious disease. Read More →

Beyond the Genetic Code: A New Way to Understand and Treat Cancer

ISB Professor Dr. Sui Huang presented a Research Roundtable challenging the traditional genetic paradigm of cancer. Drawing on systems biology, Huang proposed that cancer can arise from shifts in cellular “states” independent of DNA mutations — a perspective that could reshape how the disease is studied and treated. Read More →

In Memoriam

Remembering Dr. Charles “Chuck” Watts

The ISB community mourned the passing of Dr. Charles “Chuck” Watts on September 23, 2025. A longtime member of ISB’s Board of Directors and its recent Chair, Chuck was a trusted advisor, close friend, and tireless champion of ISB’s mission. His curiosity, generosity, and leadership left an enduring imprint on the institute. Read More →

Celebrating the Legacy of Valerie Logan Hood

ISB remembers Valerie Logan Hood, beloved wife of ISB Co-founder Dr. Lee Hood and a passionate advocate for K–12 education. Valerie’s dedication played a formative role in ISB’s education initiatives, influencing generations of students and educators. Her legacy lives on through the programs and people she touched. Read More →

Honoring the Life and Vision of Ginny Ruffner

ISB also lost a cherished member of its community with the passing of renowned artist and advocate Ginny Ruffner on January 20, 2025. Through her service on the ISB Foundation Board and her transformative artistic contributions, Ginny brought art and science into dialogue — shaping ISB’s spaces and spirit in ways that continue to inspire. Read More →

Our Community

Behind the Breakthroughs: ISB’s Postdoctoral Fellows

Postdoctoral fellows are central to ISB’s research enterprise, bringing fresh ideas, advanced expertise, and interdisciplinary thinking to some of the institute’s most ambitious scientific questions. Through mentorship, collaboration, and hands-on discovery, ISB postdocs help drive innovation while preparing for the next stage of their scientific careers. Read More →

Service Meets Science: AmeriCorps at ISB

Through its partnership with Washington Service Corps, ISB has welcomed AmeriCorps members who support education and community engagement efforts across the institute. Since 2021, AmeriCorps participants have played key roles in expanding STEM access, developing curriculum, and connecting ISB’s science to students and communities throughout the region. Read More →

Carole Ellison’s Bold Bet on Science and the Researchers of Tomorrow

Carole Ellison has supported ISB’s research and STEM programs for over a decade. She established the K. Carole Ellison Fellowship in Bioinformatics, funding groundbreaking research that has enabled young scientists to make critical discoveries. Read More →

The post 2025 Year in Review: Breakthroughs, Milestones & Moments That Defined ISB appeared first on Institute for Systems Biology (ISB).

Co-directed by ISB faculty members Drs. Sean Gibbons and Sid Venkatesh, the symposium brought together leading experts working across immunology, neuroscience, metabolism, chemistry, and microbiology to discuss recent advances in this rapidly-growing field.

The symposium builds on ISB’s interest in discovering and characterizing novel gut microbial metabolites, understanding their impacts on the host physiology, and learning how to engineer their production or consumption rates in vivo. Venkatesh’s postdoctoral work resulted in the development of microbiota-directed therapeutic foods and the identification of a gut microbial fatty acid amide hydrolase that affects satiety-related pathways in malnourished children and generates novel metabolites with pharmacological effects. The Gibbons Lab has developed widely-used tools for community-scale metabolic modeling, which have enabled personalized nutritional interventions designed to optimize butyrate production and pathobiont colonization resistance.

Throughout the day, speakers emphasized a shared shift in the field — moving beyond cataloging which microbes are present to understanding what they do, how their molecular products interact with host systems, and how those interactions might be harnessed for therapy.

The program opened with remarks underscoring the rapid maturation of microbiome science and the importance of grounding discovery in mechanism and translation. From there, the symposium unfolded across a series of talks highlighting how microbial metabolites influence health across the lifespan.

Dr. Brittany Needham explored the chemical dialogue between microbes and the nervous system, revealing how bacterial metabolites interact with host signaling pathways and contribute to neurophysiology. Dr. Giada De Palma followed with insights into gut–brain communication and visceral pain, drawing on translational studies that connect microbial metabolism to sensory signaling in disorders such as irritable bowel syndrome.

The focus then shifted to early life, where microbial exposures can have outsized and lasting effects. Dr. June Round examined how the neonatal microbiome shapes immune and metabolic development, emphasizing critical windows during which microbial signals influence long-term health trajectories. Dr. Melody Zeng extended this theme across infancy and pregnancy, presenting work that links microbiome-derived metabolites to immune tolerance, viral responses in preterm infants, and maternal–fetal health.

In the afternoon session, attention turned to diet and metabolism. Dr. Matthew Carter presented findings from the Twins Nutrition Study, a randomized clinical trial comparing vegan and omnivorous diets in identical twins. By integrating multi-omics data with mechanistic validation in model systems, Carter highlighted how dietary patterns can reshape the microbiome in ways that influence circulating metabolites and metabolic health.

Closing the scientific program, Dr. Matthew Redinbo delivered a capstone talk on gut microbial enzymes and their role in regulating drugs, hormones, and neurotransmitters. His work reframes the microbiome as an active biochemical organ, capable of modulating both local and systemic signaling molecules, with implications for drug efficacy, side effects, and homeostasis.

The symposium concluded with a lively panel discussion moderated by Gibbons and Venkatesh. The conversation tackled big-picture questions facing the field: How fast is microbiome science translating to the clinic? Should researchers prioritize deep mechanistic studies or large-scale human investigations? How much effort should be devoted to discovering unknown metabolites versus understanding well-established ones? Panelists also shared candid advice for trainees entering this interdisciplinary space and offered forward-looking perspectives on the future of microbiome-based therapies.

ISB extends its gratitude to the symposium’s generous sponsors — Applied Microbiology International, LIV, Pendulum, and Science in Seattle — whose support made the event freely accessible to a global audience. Special thanks also go to session chairs Dr. Nate Ritz, Dr. Alex Carr, and Crystal Perez, and to the ISB team behind the scenes who ensured a seamless virtual experience.

Below, you’ll find the full symposium recordings, available to watch on demand. We invite you to explore the talks in order and stay connected with ISB as we continue advancing systems biology research in 2026 and beyond. Prefer to watch all sessions in a single playlist? View the full playlist on YouTube.

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“ISB congratulates Dr. Brunkow on this extraordinary honor and celebrates her contributions to science and human health,” said ISB President Dr. Jim Heath. “Her work transformed how we think about the immune system.”

The trio was recognized for discoveries that revealed how the immune system achieves peripheral immune tolerance — including identifying regulatory T cells (Tregs) and the central role of the FOXP3 gene in their development and function. Their work reshaped modern immunology and opened new paths in autoimmune disease, transplantation, and cancer immunotherapy.

The researchers’ foundational discoveries answered a century-old riddle: Why doesn’t the immune system attack the body’s own tissues? Brunkow and colleagues established FOXP3 as the molecular key to regulatory T cells, the gatekeepers that temper immune responses and prevent self-destruction.

When Sweden Calls, Go Back to Sleep

Brunkow learned of the Nobel in unforgettable fashion. In the early hours of October 6, calls from Sweden lit up her phone — twice. Assuming spam, she muted the device. Minutes later, around 3 a.m., a photographer from The Associated Press knocked on her door. 

After some incredulous back-and-forth through the window and a glimpse of the official press release, the news landed: Mary Brunkow had won the Nobel Prize.

“The last 24 hours have been amazing, overwhelming, and exciting,” Brunkow said at a press conference held at ISB on October 7. “At first I thought it was an elaborate scam — but then I spoke with the Nobel Committee. It began to sink in.”

A Puzzling Mouse, FOXP3, and Tregs

The roots of the prize trace to Seattle-born biotech company Darwin Molecular, where Brunkow led a team integrating mouse genetics, genomics, and DNA sequencing — a bold approach in the pre-genome-browser era.

Working with colleagues at Oak Ridge National Laboratory, Brunkow and her team studied an unusual mouse known as scurfy, which developed a severe, inherited immune disorder. Their investigation revealed that the disease was linked to the X chromosome. Through careful breeding and genetic sequencing, the researchers discovered a tiny two-base-pair deletion in a previously uncharacterized gene, later named FOXP3. This discovery uncovered a critical genetic switch that helps the immune system maintain balance and avoid attacking the body’s own tissues.

In parallel, Ramsdell’s immunology group dissected the cellular consequences. Together, the efforts linked FOXP3 mutations to the loss of a regulatory T-cell program that restrains immune attack. 

Crucially, the work bridged to humans. Mutations in FOXP3 cause IPEX syndrome, a devastating pediatric autoimmune disorder, cementing FOXP3 as a master regulator of immune tolerance.

“Mary’s discovery provided the molecular mechanism behind a long-debated concept,” Heath said. “Once FOXP3 marked regulatory T cells, the field could advance at pace, touching virtually every area of human health.”

From Discovery to Impact

The FOXP3/Treg axis continues to influence medicine on two fronts:

• Releasing the brakes in cancer: Tumors often recruit Tregs to suppress anti-tumor immunity. Insights stemming from the FOXP3 pathway inform strategies that lift suppression so the immune system can attack cancer.
• Applying the brakes in autoimmunity and transplantation: Treg-based or Treg-tuning therapies aim to prevent graft-versus-host disease and quell autoimmune flares, promoting tolerance where it’s beneficial.
  
  

At ISB, those ideas dovetail with programs that connect fundamental biology to real-world health, from long-COVID immunology to population-scale microbiome and genomics efforts — many accelerated through ISB’s alliance with Providence. 

“Basic discovery is the lever arm that changes the world,” Heath noted. “Out of this one discovery comes a whole industry of ways to target and tune the immune system.”

Brunkow, who joined Darwin Molecular in 1994, began the FOXP3 journey in 1995 and published its seminal description in 2001, reflected on the team ethos that powered the work: “It was an awesome time and an awesome team. We knew we were doing something important.” 

As attention turned to Stockholm in December, she remained characteristically humble — and optimistic — about the future of science.

“Federal support has been vital to progress in medicine and basic science,” Brunkow said. “Even in uncertain times, determined optimism is how we move forward.”

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We Appreciate Your Participation and Generosity at Ignite STEM

Ignite STEM lit up ISB on November 6! Our lobby was overflowing with students, educators, ISB faculty and staff, and supporters who gathered to celebrate 25 years of ISB’s education programs.

During the first hour, guests roamed among balloon-marked stations to hear stories from students, teachers, school district leaders, and STEM professionals — each sharing how ISB programs have shaped their learning and careers.

If you missed the event or want to relive the highlights, check out this slide deck of moments from the evening.

The sit-down program featured remarks from Mary Brunkow, who reflected on the educators and mentors who shaped her Nobel Prize-winning journey, and Angie Di Loreto, this year’s Valerie Logan Leadership in Science Education Award recipient, who shared her 25-year partnership with ISB and the Bellevue School District.

Jake Valenzuela led an engaging discussion on the importance of science education, invited guests to share their own ISB connections, and delivered the evening’s fundraising appeal. Jim Heath, Lee Hood, and Nitin Baliga offered remarks tying ISB’s research and education missions together.

The Education team — Claudia Ludwig, Jen Eklund, and Caroline Kiehle — extends their gratitude to everyone who contributed to a successful event, with special thanks to the Development, Facilities, Communications, and Faculty teams.

10 interns across five ISB labs are completing research

Eight local high school students and two undergraduates are researching in a variety of areas of systems biology in the Baliga, Huang, Kane, Moritz, and Venkatash labs. Above, interns Jessica Jin, left, and Sanjna Sikka are pictured working on a laser-activated speaker at ISB.

It is relatively unusual for ISB to host so many interns during the school year. However, this year, numerous students had release time for internships, and mentors had suitable projects and bandwidth. These students will wrap up their projects by June 2026 in time for our next cohort of students to arrive for new summer research experiences.

Systems Medicine Course Materials In Demand

Seven high schools, representing nearly 300 high school juniors and seniors, are currently using our Systems Medicine 4-module series. Since we began field testing these materials, we have reached over 1,000 students across 12 school districts. 

In October, we presented instructional materials from our Personalizing Disease Treatments module at the National Association for Biology Teachers, thanks to our partner EmbiTec/MiniOne. This and previous dissemination efforts are resulting in teachers in other states using materials. 

We are also supporting teachers through a monthly Professional Learning Community. ISB faculty member Sid Venkatash presented to the group of teachers on 12/3/2025 to provide examples of how nutritional and cystic fibrosis systems medicine research is progressing.

Our Newest Curriculum Module Is a Big Hit

This fall, teacher Wendy Whitmer of Lakeside High School in Nine Mile Falls, Wash., field tested our module, Microplastics in the Arctic: Mega Problem? with her two Biology classes. Below are a few standout quotes from 9th and 10th graders.

In October, we presented in Tacoma at the Washington State Teachers’ Association conference and got many other teachers up and going with this engaging, hands-on module. In total, we’re working with 16 teachers to field test the module in middle and high school classrooms this year. Feedback has been very positive and helpful as we optimize and finalize the lessons’ content. 

Quotes in response to, “What did you like about this unit? What worked for you?”

• I liked that we got lots of days to work on a big project with a partner and that we got to use the lab.
• I liked all of it, and it all worked for me.
• What I liked about this experiment is that you could clearly see that the ice froze at different temperatures.
• It was pretty interesting to learn about all this stuff.
• I really loved learning about the causes and effects of the environments in the Arctic. It really encouraged me to do my part and have ideas about the Arctic Ocean. I also enjoyed the lab experiments.
• I liked the parts where we found potential solutions and in the lab things because it really showed what was going on.
• I liked learning about the impact we have on the world around us, and the labs worked very well to help me learn.
• I liked working on an actual project, instead of just working on a worksheet or a packet, and that worked for me, so that I’m not doing the same boring, less interactive thing over a few days.
• I have liked researching and learning all about the Arctic and microplastics, and what I can do to help.

Supporting Local School Systems to Launch the New Academic Year

ISB Education ran a workshop at the Puyallup School District‘s back-to-school institute. A group of secondary teachers from the science, math, social studies, and English departments worked together to explore student practices across the curriculum. The workshop gave teachers a practical experience in how to help their students see all the practices — the skills for doing science as a scientist would. Teachers then searched for overlaps in the other courses, generating a powerful set of practices that their students might be doing across their courses on any given day at high school. 

ISB Education is running a yearlong series, year four, in the Central Kitsap School District.  In October, all high school science teachers analyzed big data sets of students’ reflections on their learning — the n=2,000 students at each of four timepoints over two years. This is a powerful view of science teaching and learning, from which the teachers established professional growth goals for our collaborative work this year.

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The grant will support ISB’s efforts to launch Tarpon, a powerful generative AI platform designed to understand and create human T cell receptors — the immune system’s targeting tools. Tarpon distills each receptor into a compact digital fingerprint and does so for millions of T cell receptors. By connecting this analysis to genomic data or electronic health records, Tarpon allows researchers to spot subtle patterns that associate with immune dysfunction and design entirely new T cells for use as highly targeted therapeutics for challenging diseases.

“Tarpon lets us move from observing the immune system to extracting the rule sets that govern its behavior, to even designing it,” said ISB President and Professor Dr. Jim Heath, who, along with his student Daniel Chen and collaborator Dr. Yapeng Su, developed the platform. “Already Tarpon is telling us what experiments to do next, and it is helping us identify patients with dysfunctional immune systems that we would have previously missed.”

ISB was named a winner in the Pathfinder — Generative AI category, which recognizes highly innovative, mission-critical projects that leverage generative AI. ISB will receive up to $200,000 in unrestricted funding, up to $100,000 in AWS Credits, and implementation support from the AWS Generative AI Innovation Center. Awardees were selected based on several factors, including the innovative and unique nature of the project, impact on mission-critical goals, and clearly defined outcomes and milestones. 

“At AWS, we’re continually amazed by the nonprofit sector’s innovative spirit and dedication to creating positive change in our communities and around the globe,” said Rick Buettner, Managing Director of Global Nonprofits at AWS. “Through the Imagine Grant program, we’re seeing organizations embrace cloud technology in ways that fundamentally reshape how they deliver on their missions. From scaling their impact to reaching underserved communities, these nonprofits are showing us what’s possible when vision meets innovation. We’re proud to support their transformative work and help them build solutions that will benefit communities for years to come.” 

Tarpon will use Amazon SageMaker as its core engine for training the AI models, managing their versions, and making them available to researchers through a secure web app. Once a model is trained and deployed, researchers anywhere can use it in real time —  generating brand-new receptor designs at the click of a button.

“This platform will serve as a foundation for future discoveries in cancer, infectious disease, autoimmune disorders, and beyond,” Heath said, “turning the once-impossible task of mapping and engineering immune diversity into a practical, data-driven reality.”

About the Institute for Systems Biology (ISB)

The Institute for Systems Biology (ISB) is a non-profit biomedical research organization in Seattle that pioneers the integration of biology, computation, and technology to improve human health. Learn more at isbscience.org.

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The Pacific Northwest RECOVER (PNW RECOVER) hub — led by the Institute for Systems Biology (ISB) with clinical partners UW Medicine, Providence, Swedish, and Cedars-Sinai — is part of a nationwide effort to understand, define, and ultimately treat long COVID.

At a virtual town hall held on November 17, 2025, ISB President Dr. Jim Heath joined clinical co-principal investigators Dr. Helen Chu (UW Medicine) and Dr. Jason Goldman (Swedish/Providence) to share what the national RECOVER 1.0 study has uncovered so far, where the science is headed next, and how upcoming clinical trials aim to translate biology into better care.

Mapping Long COVID Trajectories in RECOVER 1.0

Heath opened the program by describing the unprecedented scale of RECOVER 1.0. Over roughly four years, 15,156 participants were enrolled across 84 rural and urban sites in most U.S. states and Puerto Rico, contributing more than 160,000 blood draws and an average of 10.6 study visits per participant. That intensive follow-up has allowed researchers to carefully document the epidemiology and symptom patterns of long COVID.

Using symptom data from thousands of participants, Heath highlighted several “trajectories” — different ways symptoms can evolve after an initial SARS-CoV-2 infection. Some people experience persistent, high-burden symptoms that clearly meet long COVID definitions. Others fall just below that threshold, slowly improve over time, or develop new symptoms months after infection. These evolving trajectories, he noted, helped justify RECOVER 2.0, a next phase designed to follow a subset of participants over a longer period.

Heath also described how RECOVER is now pairing these clinical trajectories with deep molecular data. Whole-genome sequencing and large-scale blood protein measurements are underway, enabling researchers to explore polygenic risk scores (many small genetic variants acting together), viral reservoirs, and blood-based biomarkers that may distinguish different long COVID trajectories. RECOVER 2.0, scheduled to launch in May 2026, will re-engage roughly one-third of RECOVER participants with additional blood draws and questionnaires to extend these analyses over time.

What early clinical trials are telling us

Next, Chu reviewed what RECOVER and other studies have learned so far from long COVID clinical trials. She began with several leading hypotheses for long COVID mechanisms — viral persistence, microclots and organ injury, and dysregulated immune responses — and noted that early antiviral treatment during acute COVID has been associated with lower long COVID risk in multiple studies.

Two small randomized trials at Yale and Stanford tested whether Paxlovid (nirmatrelvir/ritonavir) could treat existing long COVID symptoms. In both studies, roughly 100 participants received either Paxlovid or a placebo for 15 days and were followed for changes in symptom scores. Neither trial showed a significant benefit compared to placebo.

Within RECOVER, the RECOVER-VITAL trial is evaluating longer Paxlovid courses in several arms, with participants followed for six months and biological samples collected to look for signals of viral persistence. Results are still being analyzed.

Chu also summarized results from RECOVER-NEURO, which tested three interventions for people with cognitive symptoms — online brain training, cognitive rehabilitation, and transcranial magnetic stimulation — against two placebo-style comparison groups. Across all arms, participants showed some improvement, but there were no meaningful differences between active interventions and the comparison groups.

The next wave of long COVID trials

Goldman then turned to what is coming next in the clinical trials landscape. A recent review of clinicaltrials.gov identified 133 interventional studies for long COVID in phases one through four, testing antivirals, immunomodulators, neuroactive therapies, cardiometabolic agents, and more. Some early trials, including a monoclonal antibody study, have not shown benefit, but they have yielded valuable biological data.

Within the RECOVER-TLC (Treating Long COVID) program, four new interventions have been prioritized for upcoming national trials: low-dose naltrexone, the immunomodulatory drug baricitinib, stellate ganglion block procedures, and GLP-1 receptor agonists (a class already used for diabetes and weight management). Goldman highlighted two trials that Swedish plans to offer locally: REVERSE-LC, which will test baricitinib in 550 participants with fatigue and brain fog, and ADDRESS-LC, which will evaluate an investigational neuroactive agent called Bezisterim in 208 participants with neurocognitive symptoms.

Goldman emphasized that these trials are being designed with extensive input from people living with long COVID and patient advocacy groups, and that “under-the-hood” biological measurements — such as immune cell profiling — are crucial even when symptom outcomes are modest. Just as combination therapy transformed HIV treatment, he noted, partial signals from early trials may ultimately point toward more effective multi-drug or multi-modal strategies.

Q&A: Risk factors, symptoms and what comes next

During the Q&A, the panel addressed questions on who is at risk for long COVID, why some people never develop it, and how RECOVER 2.0 will be structured. Age, pre-existing conditions such as diabetes or heart and lung disease, female sex, and lack of vaccination or hybrid immunity were discussed as established risk factors, though many underlying mechanisms remain unclear. The most common long COVID symptom clusters continue to include fatigue, brain fog, shortness of breath, and autonomic symptoms such as lightheadedness or palpitations.

The panel also reassured attendees that prior participation in RECOVER 1.0 generally does not exclude them from future clinical trials — and in fact, their existing longitudinal data make them especially valuable to researchers. RECOVER 2.0 will be smaller and more focused, enriching for participants who still have symptoms while tying long-term clinical follow-up to ongoing molecular and genetic studies.

You can watch the event in full here or by playing the video at the top of this page.

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