Dr. Ben Ebert's Legacy of Collaborative Research Fuels Innovation at Dana-Farber
July 1, 2025
By Beth Dougherty
The mention of long-distance running or cycling might conjure images of a solo athlete on a lonely road. But for Benjamin L. Ebert, MD, PhD, these sports have almost always been group activities.
"I've done most of my running and cycling with friends and family," says Ebert, president and CEO of Dana-Farber. "There are so many memorable conversations and interactions that have happened during long runs and rides."
This unexpected take on so-called solo sports is also a window into Ebert's approach to science, medicine, and leadership. Ebert has had a remarkable career as a scientist with findings that range from practice-changing discoveries related to blood cancers to deeply mechanistic insights about how cancer drugs work. But at every step, Ebert is quick to point out that he hasn't operated alone. He has surrounded himself with talented people about whom he cares deeply, and he has encouraged those around him to do the same.
"In addition to being a brilliant scientist, Ben is a wonderful person," says Laurie H. Glimcher, MD, PhD, Dana-Farber President and CEO Emerita, who led the Institute from 2016-24.
Building a Foundation
It was not a surprise that Ebert would pursue a career in medicine. His father, both grandfathers, and great-uncle were all physicians. For Ebert, however, there was another layer. He also wanted to run a research lab, and he wanted that research to be in service of advancing medicine to benefit patients.
After studying mathematics and chemistry at Williams College, he became a Rhodes Scholar and attended Oxford University in the UK. There, he worked in the lab of a young molecular biologist, Peter Ratcliffe, MD, who would later be awarded the Nobel Prize in Physiology or Medicine alongside Dana-Farber investigator William Kaelin Jr., MD. Their work involved dissecting a fundamental human oxygen-sensing mechanism and detailing its role in cancer.
In 1989, when Ratcliffe started this journey, he didn't know his research would develop into something so noteworthy. Rather, he'd trained as a clinical nephrologist and a question had caught his eye. He knew that the kidney helps replenish blood when oxygen levels are low by making a hormone, erythropoietin.
But no one knew how oxygen and erythropoietin (EPO) were linked. So Ratcliffe found experts to help him train in molecular biology techniques. He began experimenting and training others, including Ebert.
"I learned that if there was a technology or approach that was going to move my particular scientific question forward, I needed to learn that approach, to find people who used it successfully, and to collaborate closely with the leading experts," says Ebert. "Peter Ratcliffe taught me to have the scientific courage to venture into areas I hadn't ventured into before."
In addition to being a brilliant scientist, Ben is a wonderful person.
Finding a Medical Mission
Ebert returned from the UK with a PhD, and a plan to attend Harvard Medical School. While there, he continued research related to oxygen sensing in blood cells in the lab of Frank Bunn, MD. Four years later, he completed a residency at Massachusetts General Hospital and then came to Dana-Farber in 2001 as a fellow in hematology and oncology.
During the last two years of his fellowship, Ebert joined the lab of Todd Golub, MD, at the Broad Institute of MIT and Harvard, who at the time was also a young investigator.
"I think it's fair to say that Ben took a risk by working with me," says Golub, who is also a Dana-Farber faculty member. "These were the very earliest days of functional genomics, and he was open to and excited about thinking about an old problem in a new way."
During his medical training, Ebert had homed in on myelodysplastic syndrome (MDS), a precursor condition that can lead to acute myeloid leukemia (AML), as an area of focus. He'd always been interested in blood and blood disorders, but he found this condition to be ripe for progress.
"MDS was a field that was underrepresented scientifically but there were new technological approaches that would enable significant progress to be made," says Ebert. "In addition, there was a major unmet clinical need to understand MDS and reduce the risk of AML."
Benjamin L. Ebert, MD, PhD, joined Dana-Farber in 2001 as an Institute fellow in hematology and oncology. He stands second from the left in the back row, with the rest of that year's fellows.
Integrity in Action
The novel technology at that time was RNA interference, or RNAi, which enabled investigators to disable one gene at a time in human cells. Prior to this development, most genome-wide genetic studies were done in flies and worms, not in human cells.
This technique made it possible for researchers to systematically uncover the function of every gene in specific types of human cells, including diseased cells, potentially enabling them to home in on disease-causing genes.
Ebert set out to use this tool to try to understand which genes caused MDS. He spent 18 months setting up an RNAi screen and collecting data. He even found some possible culprits.
But, Ebert recalls, he knew the RNAi screen wasn't up to par. The technique was evolving, and he was still learning to use it. During those 18 months, he learned enough to know that any data that came from what he'd done wasn't usable.
"You cannot move forward on a project unless you have full confidence that the foundation of the project is absolutely solid," Ebert says. "Otherwise, you risk publishing something you aren't sure about. It sounds easy, but it is incredibly hard to start over after investing so much time."
But start over he did, and with a year and a half of experience under his belt, the second attempt moved along rapidly. This time, the work produced a discovery, in 2008, that the loss of a gene called RPS14 led to a specific form of MDS called 5q-syndrome.
Importantly, Ebert's work was also among the first studies to show that this new, unbiased approach to understanding the genetic causes of human disease — an approach that later would morph into more sophisticated CRISPR screens — worked.
"This was a new concept, and not only did it work, but it was also generalizable," says Golub. "It is the rare person who can get their head around these systematic approaches to biology and also have the skills to do the rigorous cell and molecular biology required for a project like this. Ben was the full package."
It is the rare person who can get their head around these systematic approaches to biology and also have the skills to do the rigorous cell and molecular biology required for a project like this. Ben was the full package.
Clinically Meaningful Questions
While Ebert was interested in understanding the causes of 5q-syndrome, he also knew that patients with this condition responded well to a drug called lenalidomide, which is also used to treat multiple myeloma. Exactly how the drug worked, however, was unknown. Ebert set out to find the mechanism.
"When you start with a clear clinical observation, it's a really strong foundation for a project," says Ebert. "You know that you are studying something that's important because the drug works and makes people better."
The journey to discovery, however, was arduous. Plagued by false avenues and failures, the post-doc working with Ebert on the project asked to stop multiple times. But they kept going.
As Ebert recalls, part of the problem was that they were looking for something familiar, such as a means by which lenalidomide inhibited an active process in the disease. But eventually they recognized that lenalidomide worked in a completely unexpected way.
Rather than inhibit an enzyme, the drug redirects a key enzyme in the protein recycling system inside cells to tag and degrade proteins that contribute to the disease processes. These proteins are transcription factors, which regulate the expression of other genes.
Because transcription factors tend to be smooth with few pockets for inhibitor drugs to bind to, they were thought to be "undruggable." Degrading transcription factors opened a new way of thinking.
"Leveraging this mechanistic understanding has turned out to be an opportunity for new drug development that has led to one project after another," says Ebert, who published those seminal findings in 2014. "It has been incredibly fun and productive."
And it was transformative, says Eric Fischer, PhD, a structural and molecular biologist at Dana-Farber who has been collaborating with Ebert on this research for a decade. By deeply understanding the details of this mechanism and refining it over the years, they have laid the groundwork for drug developers in the pharmaceutical industry to devise multiple new agents with clinical potential.
"We think this next decade could be the clinical decade for protein degradation," says Fischer.
Following the Science
In parallel, Ebert continued his lab's work to understand the genetic drivers of MDS. In 2011, the team published a New England Journal of Medicine article listing a set of gene mutations found in about half of MDS cases and detailing how each mutation influenced survival and outcomes for patients. These findings pointed to possible ways to treat the condition and potentially stave off the development of acute leukemia.
As large-scale genomic sequencing tools became more powerful, it was becoming possible to learn even more comprehensively about the genetic drivers of cancer. In the MDS/AML space, a pattern emerged. Mutated genes related to the cohesin complex were implicated across multiple forms of MDS and AML.
"This complex enables two meters of genetic material to fit into a tiny space in the nucleus in a particular way," says Dana-Farber physician-scientist Zuzana Tothova, MD, PhD, who joined the Ebert lab in 2013 and took on a project to learn more about this complex. "Patients who have mutations in this complex do extremely poorly."
No one understood how the complex was connected to cancer, but new technologies in the field of epigenetics were emerging. Tothova, with Ebert's guidance, leveraged those tools and learned that this complex, when mutated, results in impaired DNA damage repair processes. That insight helped her recognize that cancers with cohesin complex mutations might be vulnerable to PARP inhibitors, which have been successful in ovarian cancers that have DNA damage repair impairments.
Based on these findings, which were published in 2021, Tothova launched an investigator-initiated clinical trial in collaboration with Dana-Farber clinician Jaqueline Garcia, MD, to test PARP inhibitors in combination with other agents in patients with cohesin-mutant MDS and AML.
"It's a dream come true to have your findings actually translated to something that could be meaningful for patients," says Tothova. "There are very few places in the world where one could do that as seamlessly as we can do it here at Dana-Farber. Ben always encouraged me to go after challenging and clinically important problems."
It's a dream come true to have your findings actually translated to something that could be meaningful for patients. There are very few places in the world where one could do that as seamlessly as we can do it here at Dana-Farber. Ben always encouraged me to go after challenging and clinically important problems.
Earlier Intervention
Ebert's work detailing the roots of MDS also led to the identification of clonal hematopoiesis of indeterminate potential (CHIP), a precursor of MDS and AML that occurs in about 15% of people over age 65. People with the condition have mutations associated with leukemia in cells of the blood or bone marrow, but those mutations are sparse and don't yet affect health. They do raise the risk, however, that cells with those mutations will grow rapidly and begin to take over, elevating the risk of MDS, AML, and, surprisingly, cardiovascular disease.
That risk varies, however, as discovered by Dana-Farber physician-scientist Lachelle D. Weeks, MD, PhD, who joined the Ebert lab as a postdoctoral fellow in 2018. Around that time, Weeks, who was trained as a bench scientist, was running a clinic at Dana-Farber to consult with patients found to have CHIP precursor mutations.
"The number one question patients asked me was, what exactly is my specific risk for progression to MDS and AML?" says Weeks. "I wanted to give them an answer."
With Ebert's help, Weeks connected to collaborators across the Institute and beyond who had the expertise Weeks needed to answer this question using data found in medical records and clinical repositories. This kind of population-based research was unfamiliar ground for Weeks and for the Ebert lab, but Ebert encouraged Weeks to learn from experts who could help her think through the question and find a way to answer it.
In 2023, Weeks published a risk stratification method for CHIP, called the Clonal Hematopoiesis Risk Score, which showed that only about 4% of people with CHIP precursors in their blood are at a very high risk of progressing to more dire conditions.
"A huge part of identifying ways to intervene early is to first determine who is at highest risk," says Ebert. "Those are the people who might benefit from clinical trials and novel ways to intervene to prevent progression to overt malignancy."
Culture of Collaboration
As Ebert's research gained momentum, it caught the attention of Glimcher. When the Search Committee selected Ebert to chair Dana-Farber's department of Medical Oncology — initially overseeing a team of 200 oncologists — he elevated an already outstanding department into one of exceptional distinction. Under his leadership, the department experienced a period of dramatic growth in the number of faculty, clinical volume, and research funding. Among his initiatives were programs to increase faculty well-being, particularly as he led the department through a pandemic, and to encourage multidisciplinary collaboration.
"I think science is more of a social engagement than people give it credit for," says Ebert. "It's a dense web of interactions, not just a few arrows from one investigation or investigator to the next."
Collaboration is central to the unique culture at Dana-Farber, which puts equal weight on research and patient care. Only together, through active collaboration between clinicians and scientists, is it possible to advance medicine for patients. Ebert's research demonstrates the incredible strides that can be made when pressing clinical questions emerge from clinical practice and are deeply and collaboratively explored the laboratory.
Looking ahead, as Dana-Farber faces another wave of growth with the advancement of a dedicated inpatient cancer hospital and the establishment of a new collaboration with Beth Israel Deaconess Medical Center, Ebert is keen to maintain and nurture this culture.
"When we were a small organization, everybody knew everybody, and you knew who to go to for collaboration," says Ebert. "As we grow, we need to create systems and opportunities to increase the interactions across the organization."
One prime example is the new Center for RAS Therapeutics, which brings basic scientists and clinical investigators together to advance treatments for patients with cancers with RAS mutations, which are found in more than 20% of all cancers and can be exceptionally difficult to treat. Other initiatives are less formal, such as mini-retreats, symposia, training, and social gatherings.
"We are always looking for ways to bring people together, to interact, become friends, become collaborators, and do really important science and medicine together," says Ebert.