Scientists and clinicians reunite for the second year of Bridge Across the Charles

From the rapid development of the mRNA Covid-19 vaccine to the creation of life-saving HIV therapies, some of the most transformative advances in medicine have come from close collaboration between clinicians and basic science researchers. Yet even in Boston — home to world-class researchers, leading clinicians, and some of the best curated patient cohorts — opportunities for sustained dialogue between the two fields remain limited. 

The annual Bridge Across the Charles event is meant to close that gap. On Nov. 24, researchers from Whitehead Institute and Massachusetts Institute of Technology (MIT) joined clinicians from Boston Children’s Hospital for the second year of this gathering, designed to bring clinicians, physician-scientists and basic scientists into closer conversation.

Co-organized by Whitehead Institute Member Ankur Jain and Ryan Flynn, an assistant professor at Boston Children’s, the event convened experts across neuroscience, immunology, cancer biology, and rare disease.

Jain, who is also an associate professor of biology at MIT, studies the molecular underpinnings of neurological disorders like ALS, Huntington’s disease, and Fragile X syndrome, and is driven to ensure that his lab’s mechanistic discoveries inform, and are informed by, clinical application.

The goal of the gathering, he noted, is to spark the kinds of “informal collisions” that lead to breakthroughs. “Most groundbreaking discoveries arise when clinical insights meet deep mechanistic exploration,” he said.
 
Ruth Lehmann, Whitehead Institute director, opened the event with remarks alongside Nancy Andrews, executive vice president and chief scientific officer of Boston Children’s Hospital. Andrews is also a Whitehead alum and a member of the MIT Corporation. Together, they reaffirmed their shared goal of advancing research that improves patient outcomes. 

“By applying diverse perspectives to unanswered questions and unmet medical needs, we create opportunities to leverage fundamental science to develop new insights about and therapies for our patients,” said Andrews.

Their remarks were followed by short research talks, where some presenters highlighted collaborations that emerged from last year’s inaugural gathering. These collaborations underscore how cross-disciplinary interactions can accelerate discoveries with real-world impact. 

One such example comes from the lab of Whitehead Institute Member Iain Cheeseman and the clinic of Boston Children’s pathologist-in-chief Mark Fleming. The Cheeseman Lab studies the molecular basis of core cellular processes: how cells grow, proliferate, divide, and function. Recently, they began applying their discoveries to understand rare diseases. 

In their latest work, the group examined a single gene that can produce different versions of the same protein. They found that each version localizes to a different part of the cell, such as the mitochondria or the nucleus, and performs a distinct function. This suggested that mutations affecting one protein version versus the other could have very different effects on disease, but there was no way to confirm it without patient data.

The story might have ended there, but through last year’s Bridge Across the Charles, Cheeseman lab members met Fleming. At Boston Children’s, he follows a small group of patients with a rare anemia called SIFD, which is caused by mutations in the TRNT1 gene — one of the genes the Cheeseman lab had been studying. 

Using anonymized patient data, the researchers identified two patients with mutations altering only one protein version. These patients had a distinct presentation of the disease, supporting the researchers’ hypothesis. “For Mark, this was a satisfying discovery because those two patients had always been outliers,” said Cheeseman. 

That collaboration is now yielding new mechanistic insights into the causes of rare genetic diseases and driving the development of computational tools at the Cheeseman Lab that clinicians could use to detect mutations that would otherwise be overlooked. 

Chris Burge, an associate professor of biology and biological engineering at MIT, also traced the beginnings of his collaboration with Mariella Filbin to last year’s gathering. Filbin is an attending physician at Boston Children’s Blood Disorders Center. “We applied for a micro-grant that same day,” said Burge. “We’ve already established a good basis for a collaboration, and [the work is] likely to evolve in interesting directions.”

After the talks this year, attendees from each side of the river with overlapping research and clinical interests paired off for deeper discussions. “We literally had to pull people away from their tables,” said Jain. “Three people have already submitted micro-grants for future discussions.”

Among them are Whitehead Institute Valhalla Fellow Aditya Raguram and Leslie Kean, director of the Pediatric Stem Cell Transplant Program at Boston Children’s. 

While Kean specializes in transplant immunology, Raguram’s lab is developing novel methods to deliver large genome-editing proteins into cells. This research could power the next-generation of therapies capable of silencing or correcting disease-causing genes. 

On paper, their work doesn’t have much overlap. But in talking, they realized the therapeutic particles Raguram is designing could have unexpected relevance for immune tolerance in organ transplantation. 

For Jain, these moments capture what the event is meant to do. “You have the interactions you expect when you’re looking for something. But then you have the unexpected ones when people didn’t know there were synergies, and they chatted and figured it out.” Those moments, he said, might just be where the next breakthrough begins.