Welcome to PNRI’s Center for Rare Disease Research
At PNRI’s Center for Rare Disease Research, we’re tackling some of the most complex challenges in medicine by investigating rare diseases–conditions that, while individually uncommon, collectively affect 1 in 10 people worldwide. Our Center for Rare Disease Research is advancing discoveries that not only improve the lives of rare disease patients but also illuminate the genetic underpinnings of more common diseases.
The Power of Rare Disease Research
Rare disease research is often a catalyst for scientific breakthroughs. By uncovering the genetic causes of these conditions, researchers gain critical insight into how genes function—and malfunction—across a wide spectrum of diseases. This knowledge drives earlier diagnoses, targeted treatments, and a deeper understanding of biology that benefits us all.
Our Research Labs
The Center’s two flagship labs—the Carvalho Lab and the Dudley Lab—are spearheading bold, innovative approaches to rare disease research. Each brings a unique focus and powerful toolkit to uncover the genetic roots of rare conditions and accelerate better diagnostics, treatments, and understanding across the biomedical landscape.
The Carvalho Lab
The Carvalho Lab at PNRI investigates the genetic architecture of rare diseases by focusing on complex genomic rearrangements—structural variants that are frequently missed by standard diagnostic methods yet play a critical role in human disease.
Led by Dr. Cláudia Carvalho, the lab uses long-read sequencing and advanced computational analysis to identify and characterize structural variants such as copy-number changes, inversions, and translocations. These rearrangements can disrupt gene function, alter regulatory landscapes, or create novel fusion genes—mechanisms often implicated in neurodevelopmental disorders, congenital anomalies, and certain cancers.
A central goal of the lab is to resolve previously undiagnosed cases by revealing these elusive genomic alterations and defining their functional consequences. By integrating high-resolution genomic maps with transcriptomic and epigenomic data, Dr. Carvalho’s team is uncovering how structural variation influences gene expression and contributes to disease phenotypes.
The lab’s work not only leads to molecular diagnoses for patients who have undergone years of inconclusive testing, but also advances our understanding of fundamental mechanisms of genome instability and gene regulation. In collaboration with clinical partners and rare disease foundations, the Carvalho Lab is translating these insights into improved diagnostics and setting the stage for future therapeutic development.
Through its focus on complex rearrangements—an often-overlooked class of variation—the Carvalho Lab is expanding the frontier of rare disease genomics and providing answers to families long left in the dark.
Learn more about the Carvalho Lab
The Dudley Lab
The Dudley Lab at PNRI develops high-throughput tools to improve diagnosis and treatment for rare inherited diseases—especially those involving “variants of uncertain significance” (VUS), which can complicate clinical interpretation and delay care.
A primary focus of the lab is urea cycle disorders (UCDs), a group of life-threatening metabolic conditions that often present in newborns. Genetic testing for UCDs frequently reveals variants that are difficult to interpret using traditional approaches. To address this, Dr. Aimée Dudley and her team use Saccharomyces cerevisiae as a genetic platform to model thousands of human variants and directly assess their functional consequences. This yeast-based system allows the lab to rapidly and accurately determine which variants cause disease and which are benign.
In collaboration with clinicians at Children’s National Hospital, the Dudley Lab has created a reference dataset of more than 1,500 UCD-associated variants and built a genetic screening tool now in use at multiple hospitals. This tool enables faster, more accurate diagnoses in critically ill newborns, often within hours—supporting earlier intervention and improved outcomes. The lab’s work also provides insights into the severity of individual variants, helping to inform personalized treatment plans and identify asymptomatic individuals at risk.
Beyond UCDs, the Dudley Lab is extending this approach to develop scalable diagnostic tools for other inherited metabolic conditions that are currently undetectable by standard newborn screening methods. By building functional variant datasets for a wider range of diseases, their work has the potential to significantly expand newborn screening panels and improve early detection of serious but treatable genetic disorders.
Through innovative applications of yeast genetics, the Dudley Lab is advancing clinical genomics and shaping a future in which rare diseases can be identified and treated earlier—transforming outcomes for families worldwide.
Events
From monthly seminars to annual symposia, PNRI brings together scientists, clinicians, and advocates to share ideas, spark collaboration, and advance genetic research. Learn more about our ongoing series and special events below.
Science Matters Seminars
PNRI’s Science Matters free, virtual, monthly seminars feature discussions with scientists around the globe about exciting research in genetics, genomics, and evolutionary biology with important societal impact.
Topics include research on the genetics of ethnically diverse populations, diseases afflicting vulnerable or underserved groups, and efforts to expand the diversity (broadly defined) of research subjects or the scientific workforce.
The seminars are free to attend and open to the scientific community and anyone interested in learning more about genetics.
Rare Disease Day Scientific Symposium
In honor of Rare Disease Day on February 28, 2025, PNRI proudly hosted our inaugural rare disease research scientific symposium–in partnership with Seattle Children’s Research Institute and the University of Washington–to celebrate the rich local network of rare disease researchers, clinicians, and patient advocates in Seattle.
Click the button below to explore the full lineup of scientific talks and poster sessions—and watch the video for a glimpse of the energy and momentum that made this event so impactful!
Inside Rare Disease Day 2025
On Rare Disease Day 2025, scientists, clinicians, and advocates gathered for a powerful symposium hosted by PNRI and Seattle Children’s Research Institute. This event spotlighted groundbreaking discoveries, innovative collaborations, and a shared commitment to advancing research and improving the lives of those affected by rare diseases. Watch the video to see how this vibrant community is working together to accelerate progress.
Collaborate With Us
PNRI is committed to advancing rare disease research through collaboration. Whether you’re a researcher, a philanthropist, an advocate, or a member of the rare disease community, we invite you to partner with us. Together, we can accelerate discoveries that change lives. Explore the ways to collaborate with us:
Research Partnerships
Research partnerships at PNRI’s Center for Rare Disease Research provide critical opportunities to collaborate on pioneering genetic discoveries. By working with institutions like Children’s National Hospital, Baylor College of Medicine, and the Karolinska Institutet, PNRI integrates cutting-edge research with clinical expertise to accelerate the development of new diagnostic tools and treatments. We also partner with global initiatives, such as the NHGRI-funded GREGoR consortium, to uncover the genetic causes of unexplained rare disorders, driving innovation in rare disease research. If you’re interested in exploring a research partnership with us, please reach out at raredisease@pnri.org.
Philanthropy and Sponsorships
Philanthropic and sponsorship opportunities at PNRI’s Center for Rare Disease Research offer powerful ways to advance groundbreaking science. Unrestricted gifts provide flexibility to accelerate discovery, while event sponsorships—like Rare Disease Day and Science Matters—offer recognition and support for critical research. Matching gifts and workplace giving programs can further amplify impact. Every contribution brings us closer to better diagnostics, treatments, and lasting change for patients and families.
Patient Advocacy and Outreach
Patient advocacy and outreach opportunities at PNRI’s Center for Rare Disease Research offer powerful ways to collaborate in raising awareness and supporting rare disease communities. Through partnerships with groups like the NW Rare Disease Coalition, PNRI works to advance research, shorten the diagnostic journey for patients, and expand treatment options.
PNRI’s annual Rare Disease Day symposium is a meaningful opportunity for rare disease organizations to connect, share their work, and engage with researchers, clinicians, and advocates. Organizations interested in participating in the 2026 event can email us at raredisease@pnri.org to learn more.
Educational Programs
PNRI’s educational programs foster the next generation of scientists through opportunities like the Summer Undergraduate Research Internship (SURI), where students gain hands-on experience in genomics and biomedical research. SURI participants work closely with PNRI scientists, contributing to real-world projects that drive advancements in rare disease research. Additionally, all PNRI principal investigators are affiliate faculty at the University of Washington’s Department of Genome Sciences, providing students and trainees with access to a robust academic network and mentorship from renowned experts in the field.
Families Are Powerful Partners in the Push for Progress
In this 60-second video from PNRI’s Rare Disease Day 2025 scientific symposium, two parents share why research matters—and how their lived experiences are helping to drive it forward. Their voices represent the strength, urgency, and hope at the heart of the rare disease community.
Contact Us
Have questions or want to learn more? Click the button below to reach out to us at raredisease@pnri.org
Mailing Address
Pacific Northwest Research Institute
720 Broadway, Seattle, WA 98122
Phone
(206) 726-1200 (local)
(800) 745-1527 (toll-free)
(206) 726-1217 (fax)
PNRI Rare Disease Research News and Media
Rare Disease, Real Progress: Season 2 of PNRI’s Podcast Is Here
Listen now to PNRI Science: Rare Disease, Real Progress – our latest podcast series featuring conversations from our 2025 Rare Disease Day Symposium with scientists, advocates, and industry leaders accelerating rare disease research.
Advancing Genetic Research, Together: Our FY24 Annual Report
PNRI’s FY24 Annual Report is here! See how we’re advancing genetic research, expanding programs, and shaping the future of human health.
Rare Disease Day 2025: Accelerating Discovery Together
PNRI’s inaugural Rare Disease Day symposium ignited bold collaborations to accelerate rare disease research. See how scientists, clinicians, and advocates are driving breakthroughs!
PNRI Rare Disease Research Publications
Proud to Partner With
We are grateful to partner with organizations and institutions committed to rare disease advocacy and research. Together, we are making an impact on the rare disease community.
