Scientists and clinicians convene to bridge gaps in rare disease research and care

Rare disease treatment and care relies on the combined efforts of clinicians working to interpret mutations that may explain their patients’ symptoms, researchers developing new tools to understand gene function, and families searching for answers that will take years to find. Yet these people rarely find themselves in the same room.

BridgeRD, held at Whitehead Institute on Nov. 12—co-organized by graduate students Jimmy Ly of the Cheeseman Lab at Whitehead Institute and Dawn Chen of the Chen Lab at the Broad Institute—set out to change that.

The idea came from a conversation over coffee. Ly and Chen met last June at the RNA Society meeting in San Diego, where Ly discussed his research on alternative protein products produced from single genes, which revealed how mutations affecting alternative proteins can lead to rare, hard-to-diagnose diseases. Chen, who develops CRISPR-based tools to study how genetic variation causes disease, has long been passionate about improving the speed and quality of genetic testing for rare disease patients navigating diagnostic odysseys.

Their conversation revealed a shared frustration: scientists and clinical geneticists often work on complementary pieces of the same puzzle but rarely find opportunities to interact.

“We were talking about how we could help diagnose more patients, and we just said, let’s do it. Let’s host a workshop to bring everyone together,” Chen says. With support from Claudia Chu and Wesley Leong at the Broad Institute, BridgeRD finally took shape.

Over one hundred people joined the event, both online and in-person, representing the range of stakeholders Ly and Chen hoped to bring together: functional geneticists, computational and AI experts, clinicians, and family members of people with rare diseases.

Keynote speaker Gilad Evrony, an associate professor in the Departments of Pediatrics and Neuroscience at New York University (NYU), highlighted the “long tail” problem in rare disease diagnostics. As sequencing technologies continue to advance, clinicians are identifying increasingly rare—and often entirely novel—gene variants. While many disease-causing variants remain to be discovered, each affects a very small patient population, resulting in sparse data to link genes and diseases. Progress will slow down, he explained, unless researchers studying gene function and clinicians interpreting patient genomes collaborate more consistently.

This gap is precisely where Whitehead Institute researchers, including Ly, hope to play an essential role: their work studying protein function can generate insights and experimental tools that clinicians can use to interpret genetic mutations in their patients.

Ly’s recent study in Molecular Cell, for example, conducted in collaboration with Boston Children’s Hospital, revealed that different protein versions produced from a single gene can carry out separate functions and contribute differently to disease. It is from these findings that the Cheeseman Lab is now developing SwissIsoform, a computational tool designed to help clinicians detect mutations in specific protein variants that would otherwise be missed.

Building on this spirit of collaboration, the in-person afternoon workshop invited attendees to break into smaller groups to explore a central question: “What is a problem in the rare disease space you want to work on?” The exercise sparked further discussions about shared challenges, unmet patient needs, and opportunities for new collaborations between clinicians and scientists.

For Whitehead Institute, BridgeRD reflects a broader commitment: investing in basic science research that directly advances human health. This event is just one example of how Whitehead Institute researchers are contributing to breakthroughs in biomedicine, while serving as the connective tissue between scientific insights and tangible patient outcomes.