A clinical genomicist harnesses team-based science to help rare-disease patients

And though there is still a long way to go — about half of rare disease patients remain undiagnosed — Rehm’s fingerprints can be found on many of the standards and tools that have allowed clinical geneticists to increase their diagnostic success rate over the last 20 years. She led groups that developed a consistent language that scientists and clinicians everywhere use to interpret genetic variation the same way, and helped build a database used by every clinical lab in the world to return more results to more patients. A skilled organizer and community-builder, Rehm has helped change the culture in clinical genetics, showing labs the value in data-sharing and helping them to implement it in a consistent way. She has been a key player in ushering in a new era of collaboration, in which each lab has at its disposal the knowledge of other labs. 

“Heidi is a true force to be reckoned with: When she has an idea, or more — an ideal, she will push until she sees it through. But she also has such positivity and takes everyone on the journey with her, making sure they see the value of her vision,” said Nicola Whiffin, an associate professor at the Big Data Institute in Oxford, UK who collaborates with Rehm as a visiting researcher. “That’s what makes her so convincing. I don’t think anybody can really argue with Heidi.”

Rehm’s clinical work and research inform each other: Not only has she helped return diagnoses to thousands of rare-disease patients, but she has also contributed to the discovery of hundreds of new disease genes.

“Heidi has really changed the world for rare-disease patients,” Whiffin said in 2022 when she introduced Rehm as a recipient of the Curt Stern Award from the American Society of Human Genetics, which recognizes scientists who have made remarkable contributions to the field over the past decade. “Her impact on the genomics field simply cannot be overstated.”

At the Broad, Rehm wears many hats: chief medical officer for Broad Clinical Labs, a co-leader of Broad’s Center for Mendelian Genomics, and head of the Translational Genomics Group, a research effort that aims to understand the genetic basis of rare disease. She is also the chief genomics officer at Mass General and a professor of pathology at Harvard Medical School. Outside her home institutions, she has leadership roles in the Global Alliance for Genomics and Health (GA4GH), the Matchmaker Exchange, The AllofUs Research Program, and the Genome Aggregation Database (gnomAD) — all of which, she says, address the same goal.

“Every step I’ve taken over the years — every grant I’ve applied for and role I’ve played — has been about delivering better care to patients,” Rehm said. “There are so many inefficiencies in how we learn about a person’s genetics, and that’s not all going to change overnight. But gathering the collective intelligence, drive, and effort of the community is going to allow us to do something that is greater than the sum of its parts.”

As a child growing up in Lake George, New York, Rehm was ambitious and active, a good student and athlete who spent her free time hiking, canoeing, and camping in the Adirondack mountains. Her father, a high school biology teacher, filled their house with snakes and frogs he brought home from school over the summer. Her mother liked to get things done and made lists for everything, a trait both Rehm and her sister inherited. 

From her first biology course in high school, Rehm loved the logic of genetics: the clear trajectory from a simple code of DNA to RNA to proteins — and how disrupting that process could lead to disease. In 1993, after earning a bachelor’s degree in molecular biology and biochemistry from Middlebury College, Rehm moved to Boston to pursue a PhD in genetics. At Harvard Medical School, Rehm joined the lab of Cynthia Morton, studying the genetic basis of hearing loss, and later the lab of David Corey as a postdoctoral fellow. 

Even as a graduate student, Rehm was already showing her penchant for organizing and bringing people together. She formed the Division of Medical Sciences Mountain Club and organized outdoor adventures for other graduate students, and persuaded companies to donate medical supplies to families in need in Costa Rica when she’d traveled there for research.

In 2002, as Rehm was beginning her postdoc, Raju Kucherlapati, a colleague at Harvard, asked her to start a clinical lab at what was then called the Harvard-Partners Center for Genetics and Genomics that would do genetic testing for people with disease and help determine the cause of their conditions. 

It was a chance to fulfill her dream of helping patients. “I wanted to catalog every rare disease and all the underlying disrupted genes,” remembers Rehm. “I wanted to make a difference for patients.”