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COVER PHOTO BY FAITH NINIVAGGI
Behind the Nobel moment
On Monday, Oct. 7, 2024,
the UMass Chan Medical School community awoke to the news that Victor R. Ambros, PhD, the Silverman Chair in Natural Sciences and professor of molecular medicine, had been named co-recipient of the 2024 Nobel Prize in Physiology or Medicine for his co-discovery of microRNA, with longtime collaborator Gary Ruvkun, PhD, professor of genetics at Harvard Medical School and Massachusetts General Hospital. In this special edition of @umasschan magazine, learn more about the science, the scientists and the promise of microRNA.
The science
Victor Ambros’ innate curiosity led him to investigate the “schmutz” at the bottom of one of his experimental gels in the early 1990s. These tiny bits of unidentified residue were left over after all the larger DNA, RNA and protein molecules had been separated out of a cell culture mixture and sorted by size for analysis. Amid this blob of cellular detritus, it turned out, was the product of a worm gene. And what became the first identification of what is now known as microRNA.
Looking to explain how a genetic mutation caused C. elegans—the aforementioned worm—to remain stuck in a juvenile state, Dr. Ambros knew from previous work that this gene somehow controlled the output of a protein necessary for cellular development. Worms with this mutant gene were stuck developmentally, repeating the first larval stage over and over.
Expecting to find that the gene coded for a very small regulatory protein that would stop this stage of development, Ambros and colleagues found something entirely different.
The gene encoded for a very short, single-stranded RNA molecule that scientists had yet to identify—microRNA. This particular microRNA was responsible for putting the brakes on the machinery necessary for creating the protein that would allow the worm to mature normally.
In 1993, however, microRNA seemed more an oddity than a breakthrough, in part, because the gene existed only in the worm. Then, in 2000, Gary Ruvkun, PhD, professor of genetics at Harvard Medical School and Massachusetts General Hospital, identified a second microRNA in C. elegans. By 2001, Ambros and other scientists had identified multiple microRNAs in worms, flies and humans.
Top: The MJ Devices PPI-100 pulsed field electrophoresis controller device enables the detection and isolation of very large DNA molecules, accelerating chromosome walking—a technique used to clone DNA to map and sequence a chromosome— to the lin-4 gene. The unit pictured was used by the Ambros lab in the discovery of microRNA and now resides in the Nobel Museum in Stockholm.
Middle: Investigating the tiny bits of unidentified residue in experimental gels led to the first identification of what is now known as microRNA.
Bottom: The tiny but mighty Caenorhabditis elegans , holder of untold biomedical secrets, is slowly revealing clues about human biology.
PHOTO: VICTOR AMBROS
PHOTO: FAITH NINIVAGGI PHOTO:
The scientists
Victor Ambros, PhD
Victor Ambros, PhD, has always been intensely curious, fascinated by how things work and eager to understand the world around him. As a teen, Dr. Ambros made his first forays into science as an amateur astronomer. His observations that shadow bands were visible four minutes before and three minutes after the totality of a solar eclipse were published in Sky and Telescope in the spring of 1970.
“That’s the first time I think I felt like a real scientist,” recalled Ambros.
Following his curiosity, Ambros shifted his focus from astronomy to biology after observing fellow students perform wet lab experiments while he was an early undergraduate at the Massachusetts Institute of Technology, where he earned a Bachelor of Science in biology in 1975. He continued his graduate studies at MIT, earning his PhD in 1979 in the lab of David Baltimore, PhD—also a Nobel laureate—and completing a postdoctoral fellowship in the lab of H. Robert Horvitz, PhD—yet another Nobel laureate—in 1983. As a postdoc, Ambros focused on genetic pathways that direct developmental timing in the worm C. elegans
Ambros joined the faculty at Harvard Medical School in 1984 and continued to work with the model C. elegans. In 1992, he joined the faculty at Dartmouth Medical School, where he remained until joining UMass Chan in 2007.
Gary Ruvkun, PhD
Ambros and Gary Ruvkun, PhD, professor of genetics at Harvard Medical School and Massachusetts General Hospital, met while the two were postdoctoral fellows in the lab of Dr. Horvitz at MIT. Also interested in how the genome acts as an instruction manual for all the cells in the body despite the vast differences in cell types and characteristics, Dr. Ruvkun began a longtime collaboration exploring how microRNA works with Ambros. They remain friends to this day.
Ruvkun received a Bachelor of Arts in biophysics from the University of California Berkeley in 1973. After graduation, he bounced around for a time, working for a tree-planting cooperative in Oregon, traveling through Latin America and eventually spending a year as a nuclear medicine technician at the University of California San Francisco before embarking on graduate school in 1976. He received his PhD in biophysics from Harvard University in 1982, where he investigated bacterial nitrogen fixation genes.
In 1985, he joined the faculty at Massachusetts General Hospital and Harvard Medical School where he continues to teach and conduct research today.
Top: Victor Ambros is presented with his Nobel medal and diploma by King Carl XVI Gustaf of Sweden.
Middle: Gary Ruvkun, PhD, delivers his Nobel Lecture in Stockholm.
Bottom: Dr. Ambros and Dr. Ruvkun catch up at the UMass Club in Boston the afternoon of the Nobel announcement.
The promise
The growing awareness of microRNAs and their functions has transformed the study of molecular biology. Scientists never imagined that such a tiny piece of RNA could be capable of such astonishing and powerful things. This has had important consequences, not just in the ability of researchers to more quickly and efficiently perform experiments, but in their basic understanding of the biology of health and disease.
Following the discovery of microRNA, scientists quickly went to work applying it to lab research, where it can be used as part of the process to increase or decrease production of targeted genes. By acting as a “molecular probe,” microRNA can target and downregulate the expression of a specific gene, allowing researchers to observe the resulting changes. From here, scientists can infer the function of selected genes in a cell or organism and confirm that with other experimental techniques.
Essentially, by manipulating microRNA expression, researchers can study the impact on the target gene’s activity and its downstream biological processes more quickly and efficiently than previous technology allowed.
When Ambros and his lab discovered microRNA, its broad implications for human biology weren’t immediately apparent. Scientists now know the ability of these tiny RNA molecules to regulate or silence gene expression has a profound and far-reaching impact on most biological processes governing health and disease, including growth and development, aging, cancer, diabetes, heart disease, Alzheimer’s disease, schizophrenia and many others.
Top: Scientists now understand that the ability of these tiny RNA molecules to regulate or silence gene expression has a profound and far-reaching impact on most biological processes governing health and disease. Photo: Image from “The C. elegans Heterochronic Gene lin-4 Encodes Small RNAs” 1993 Cell paper.
Middle: Dr. Ambros has been spending more time in the lab these days doing the experiments he loves, excited by advances that accelerate the speed at which results are available.
Bottom: Rosalind “Candy” Lee and Ambros have connected with the Zoltan family, whose son Daniel has Argonaute syndrome, a potential target for microRNA therapeutics. From left: Lee; Ambros; Melanie Barton-Zoltan; and Tara, Daniel and Erik Zoltan.
PHOTO: JOHAN
PHOTO: FAITH NINIVAGGI
Victor Ambros and Rosalind (Candy) Lee: A life in microRNA
By Jim Fessenden
Afew years ago, 2024 Nobel laureate Victor Ambros and his wife and scientific collaborator, Rosalind “Candy” Lee, purchased a washer and dryer set.
Like many of the items around the Ambros-Lee household, the set had been given a new life by the couple, who bought it second-hand from a gentleman who had refurbished it. After installing the machines, putting one on top of the other and hooking up the plumbing, like good scientists, they tested their handiwork.
“All we could hear was this loud bang, bang, bang,” said Dr. Ambros, the Silverman Chair in Natural Sciences and professor of molecular medicine at UMass Chan Medical School.
With an instinct to reuse and repurpose and curious about what was causing the noise, the pair, like many of us would, turned to YouTube for answers. They scrolled through and watched videos on how washers work and how to repair them. Having learned what they could, they unhooked the hoses and began meticulously taking the machine apart, removing the agitator and inspecting the motor, looking for the source of the noise.
“And so, here we are, two people in their 60s, taking the dryer off the washer and then taking the washer away,” said Ambros, glancing quickly at Lee to confirm he’s remembering correctly. “And then moving the washer out and taking it apart.”
It wasn’t a difficult job, but working in a confined space and dealing with water made the task challenging. Ambros and Lee eventually discovered an old screwdriver clanging around inside the barrel of the washer.
“Apparently it had fallen in while the repairman was working on it,” said Ambros.
Inside the lab, the husband-and-wife scientific team operate in a similar fashion—bouncing ideas off each other, diagnosing problems and plotting solutions.
“That’s how we were educated,” said Lee, who graduated from the Massachusetts Institute of Technology in 1976 with a degree in chemistry, the same year she and Ambros married. “The core of what we did at MIT, no matter what field you studied, was all about problem solving.”
Ambros, who earned his undergraduate and graduate degrees from MIT, added, “The idea is, you’re always the amateur. You don’t have to be an expert; you can go and find an expert and find out what they might suggest. You find the resources you need to solve the problem in front of you and develop the experience along the way. We have this style of approaching problems, where it’s an interesting puzzle, whether it’s a dishwasher, guitar or science.”
In the beginning
At home, Lee tends to be the idea person, developing projects, such as refurbishing a washing machine, and it’s Ambros who’s the craftsman and tactician. In the lab, however, Ambros takes on the role of strategist and Lee is the craftsperson, designing and executing bench experiments.
It was Lee, now a semi-retired senior scientist at UMass Chan, who was the first author, along with Ambros and Rhonda Feinbaum, PhD, then a postdoc in the Ambros lab, on the pivotal 1993 Cell study credited with identifying the first microRNA.
Now recognized as a groundbreaking discovery— revealing a new principle of gene regulation that turned out to be essential for multicellular organisms, including humans—the identification of the first microRNA almost didn’t happen. And likely wouldn’t have if not for Lee.
Photography by Faith Ninivaggi
After working in various labs around Boston and Cambridge for several years, Lee joined the Ambros lab in 1987. She began working on the lin-4 project in 1989 only after the postdoctoral student who was originally pursuing the project left after three months because it was moving so slowly.
At a time when simply cloning a gene could take several years, even with the most advanced technology available, not many graduate or postdoctoral students wanted to spend a large chunk of their early careers pursuing a project that might not culminate in a publication, said Ambros, which can be key to moving their careers forward.
“The fear was that after cloning lin-4, it might turn out to be just a curiosity of C. elegans, and not terribly instructive about development, let alone biology,” Ambros said.
As a result, it was Lee and Dr. Feinbaum who designed the experiments and performed the painstaking work of cloning the lin-4 gene to identify its sequence.
“There are not many who could have taken on this project . . . it’s rare to have a technician who’s as talented and accomplished, with 10 years of experience, as Candy is in the lab.” • Victor Ambros, PhD
“There are not many who could have taken on this project,” said Ambros. “It’s rare to have a technician who’s as talented and accomplished, with 10 years of experience, as Candy is in the lab. It really was the perfect storm.”
It took several years, but with each successive experiment, they found the sequence for lin-4 becoming unexpectedly smaller and smaller.
“Even as a protein gene, we knew this was going to be a small protein,” said Ambros. “So, we felt we were on to something really interesting.”
Following their curiosity
The story of microRNA’s discovery begins in the lab of Ambros’ postdoctoral adviser and 2002 Nobel laureate H. Robert Horvitz, PhD, who, along with his collaborator and co-Nobelist John Sulston, PhD, had worked out and annotated the cell-by-cell development of C. elegans in real time. It turns out that every worm goes through the same cellular development at precisely the same time without fail. Given the predictability of this process, Ambros began studying abnormal worms that showed a disrupted developmental cycle with the goal of teasing out the mutant gene, its product and biochemical activity, with the goal of relating these back to the abnormal behavior.
“It is an unbiased approach to science,” said Ambros. “You find a mutant and you follow that mutant and find out what it can teach you about that system.”
It was while investigating one of these developmentally abnormal C. elegans that microRNA was discovered. Looking to explain how a mutation to the lin-4 gene caused C. elegans to remain stuck in a juvenile state, Ambros knew from previous work that this gene somehow controlled the output of the lin-14 protein. Worms with mutant lin-4 had persistently high levels of lin-14, which caused them to repeat the first larval stage of development without ever progressing to the next stage.
Expecting to find that the lin-4 gene coded for a very small regulatory protein that would stop production of the lin-14 protein, which in turn would allow the worm to progress to the second larval stage of development, Ambros and colleagues found something much different. It wasn’t until a colleague at a floor meeting presentation, seeing the “schmutz” at the bottom of one of Ambros’ gels, suggested looking at even smaller molecules that the lin-4 mutation was narrowed down to 22 nucleotides.
Because of the size, Ambros and colleagues knew this wasn’t a protein. Instead, lin-4 encoded for a very short, single-stranded RNA molecule that scientists now know as microRNA. This microRNA was responsible for putting the brakes on the machinery necessary for creating the lin-14 protein. As a result, worms with a mutated lin-4 gene were unable to produce the microRNA necessary for shutting off the lin-14 gene that would allow the worm to mature normally.
However, it seemed that the initial fears that lin-4 was only an oddity of C. elegans might prove to be true. Then, six years later, Gary Ruvkun, PhD, professor of genetics at Harvard Medical School and Massachusetts General Hospital and co-recipient of the 2024 Nobel Prize in Physiology or Medicine, identified let-7, a second microRNA in C. elegans. By 2001, Ambros and other scientists had identified multiple microRNAs in worms, flies and humans.
Today, we know that microRNAs are evolutionarily ancient and regulate gene activity in all cells as part of the RNA interference pathway (for which UMass Chan Distinguished Professor Craig C. Mello was awarded the 2006 Nobel Prize in Physiology or Medicine). Researchers have now identified more than 1,000 unique human microRNAs that are responsible for regulating more than half of all human genes.
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Introducing Ambros to the Swedish audience prior to his Nobel lecture on Dec. 7, president of the Karolinska Institute Annika Östman Wernerson, MD, noted how the discovery of microRNA highlights the importance of curiosity-driven research.
“This discovery of fundamental new mechanisms of gene regulation would probably not have been if goals for the research were predetermined,” said Dr. Östman Wernerson.
It was curiosity, and not a predefined outcome, that led Ambros and Lee to the discovery of microRNA.
That’s one of the problems with sciences today, said Lee. “Nobody wants to fund curiosity-based ideas anymore. They want to fund a goal. And when you put the constraint of producing a product on science, then you’re going to be biased to that outcome. You might try to force something that isn’t there or miss something you hadn’t considered.”
At home
Over more than three decades as investigators at Harvard University, Dartmouth College and UMass Chan, Ambros and Lee somehow found time to raise three sons. Today, their children are grown and have kids of their own. The four grandkids, all under 10 years of age, are frequent visitors to Ambros and Lee’s homes in Central Massachusetts and New Hampshire. The families often spend time together in New Hampshire where Ambros still spends time pursuing the astronomy that first got him interested in science as a teen.
For Lee, who has a large extended family, having children was always something that she felt strongly about.
“Family, and being Chinese, is really important for my identity,” explained Lee. “That’s something that I’ve tried to impart to my kids and now my grandkids. I’d like them to know they’re Chinese and we celebrate Chinese New Year and other events.”
Recently, Lee found a Chinese dragon dance head at the Wachusett Recycling Center where she volunteers most weeks. “When that came in, I was like, when you put a price on that, I’m buying it. And they did, they saved it for me.”
Once again, Ambros and Lee went to work making something new out of something otherwise intended for a landfill.
Victor Ambros, PhD, and Rosalind “Candy” Lee at their home in Central Massachusetts.
“Victor and I got together, we made a back and hot glued some sequins on it,” said Lee, an avid quilter who has a workshop that Ambros built over their garage in Holden.
The salvaged dragon dance head was a hit with the grandchildren at Lee’s 70th birthday celebration.
“We wrangled all the grandkids under it, they were moving in all directions,” recalled Lee happily. “Then there was this one moment when they all got under there, with some help from the older kids, and they were all moving in the same direction, and then they all scattered again.
“It was a really nice moment,” said Lee in her understated style.
Likewise, Lee’s large extended family has become an important theme in Ambros’ life. “She had a very cohesive extended family,” he said. “People were always visiting each other, especially before we had children. A lot of them live around Boston and Waltham, but we’d go and visit Candy’s aunts and uncles and cousins in Washington, D.C., and Philadelphia. That’s really been a big blessing for me, right from the beginning.”
Growing up in a scientific household with parents doing Nobel caliber research, however, didn’t predispose their children to science.
“In some ways, maybe, having two scientists working together might have been sort of unfortunate,” explains Lee. “It might have been a turn off.”
The closest any of their children got to science was their oldest, who earned an undergraduate degree in genetics, went to law school and became a life sciences licensing attorney. The two others have careers as a computer programmer and public administrator, respectively.
Coming to UMass Chan
During their early years at Harvard and Dartmouth, it seemed there were hurdles constantly being placed in front of them that took them away from doing actual science. That changed substantially when the duo came to UMass Chan in 2007
“Before we even set foot on campus, the respect we received from people like the chancellor and Mike Czech [founding chair of the Program in Molecular Medicine] was something we hadn’t experienced before from an administration,” said Lee. “There was just a sense of positivity, of ‘what can we do, how can we help you,’ that was different.”
“Before we even set foot on campus, the respect we received from people like the chancellor and Mike Czech was something we hadn’t experienced before from an administration.”
When home, the two would often talk about work, just off the top of their heads, as things came to them. For instance, if there was a problem in the lab, such as an experiment not working out as planned or a piece of equipment that’s broken, it comes up in conversation.
•
Rosalind (Candy) Lee
“We probably didn’t talk about the joy of doing science as much as we could have,” said Ambros. “There was always some problem that needed addressing and for a kid, that doesn’t sound like a lot of fun.”
Opposite: Lee watches as Ambros adjusts one of the guitars he rebuilt.
It wasn’t just the support of the administration that impressed Ambros and Lee, however. The collaboration and collegiality of the faculty and the sense that everybody was pulling in the same direction throughout the institution was profoundly different than their previous experiences.
“It really is extraordinary, what the administration and UMass Chan have cultivated here,” said Ambros. “It’s a contrast in almost every dimension to what our experience had been.”
People were more than just willing to talk about science, share ideas and collaborate. At UMass Chan, equipment was routinely shared across labs and faculty would take the time to teach their colleagues how to use it. Everybody, right down to the building manager, Mike Gregory, was welcoming, responsive and excited to be a part of what was happening and the science that was being done, explained both Ambros and Lee.
“What came across loud and clear, is that UMass Chan is a place where people were having fun doing science and that wasn’t something we had experienced for a very long time, unfortunately,” said Ambros.
Part of the unique atmosphere at UMass Chan, according to both Ambros and Lee, is a result of its relative youth as an academic medical center. To compete with more established institutions, UMass Chan did things differently. It recruited and nurtured younger faculty more than its competitors. It also found ways to do more with less, be nimbler and more efficient.
“Younger faculty, like Craig Mello, were encouraged to pursue ideas like RNAi,” said Ambros. “The administration and senior faculty supported him when he wanted to follow this crazy new phenomenon without knowing
At 71 years old, and with Lee already semi-retired, Ambros is naturally wondering when he might take a step back from the lab and start thinking about retirement. But the advent of CRISPR and other gene editing systems has changed how laboratory science is done. In the last few years, Ambros has been spending more time in the lab, doing experiments he loves.
“It feels great because you do a little experiment and you get results so fast,” said Ambros, getting excited. “That’s been one of the biggest changes in the lab: the speed with which we can do things.
“It’s been great to get back into the lab and become competent at some of these techniques that I was really rusty at or had never tried because I’m from an older generation,” he said. “It’s good to have that feeling of competence and the confidence that come with doing something and seeing it to completion.”
Lee added, “I can see him getting sucked into that because it’s not a long-haul sort of thing like it was 20 or 30 years ago. He’s offering to do experiments for other
people or make [C. elegans] crosses for people, making mutations, the things I used to do. He’s having so much fun doing them.”
The other contributing factor to Ambros’ newfound excitement is his recent involvement with the AGO Alliance, a foundation dedicated to curing a new class of neurodevelopmental disorders called Argonaute syndromes, which are caused by microRNA disruption.
In 2021, a team of researchers led by Amélie Piton, PhD, associate professor of genetics and pathophysiology in neurodevelopmental disorders at the Institute of Genetics, Molecular and Cellular Biology in Strasbourg, France, described the first Argonaute related syndrome in humans caused by a mutation in the AGO1 gene. Meanwhile, a team led by Davor Lessel, MD, PhD, head of the Institute of Human Genetics at University of Regensburg in Germany, and Hans-Jürgen Kreienkamp, PhD, professor of human genetics at University of Hamburg in Germany, discovered in 2020 an AGO2-related syndrome, now known Lessel-Kreienkamp or Leskres syndrome.
This year, Ambros and colleagues reported in the Proceedings of the National Academy of Sciences that the gene-silencing work of the RNA interference process is disrupted by mutations associated with Argonaute syndromes. Specifically, Ambros and colleagues showed single amino acid changes found in mutations associated with the newly identified Argonaute syndromes globally disrupt the microRNAmediated silencing process.
These genetic mutations, studied by Ambros and colleagues in the C. elegans model, cause an organismwide disruption of microRNA levels and messenger RNA translation, impacting hundreds of different genes, some of which are associated with neurodevelopment. These findings promise to help inform clinical and translational researchers in their pursuit of a treatment for Argonaute syndromes.
Even though he refurbishes and makes acoustic guitars as a hobby, Ambros admits he doesn’t play much or very well. “I can strum a few chords, but I’m always amazed when my son picks up one of the guitars and plays. It sounds so much better than when I do it.”
Lee added, “I keep trying to get him to take lessons because he’s never had any formal training.”
“There are so many people who are committed to this, it’s profound, to have an opportunity to contribute something, in our own small way.”
•
Victor Ambros, PhD
“We’re at the end of careers,” said Ambros. “And we have this astonishing opportunity to have an impact on a human disease in a very direct way. We’re directly involved in studies and things are moving so fast. There are so many people who are committed to this, it’s profound, to have an opportunity to contribute something, in our own small way.”
Hanging on the wall of Ambros and Lee’s living room is a Tokai guitar. Among the many things Ambros learned from his father, Longin Ambros, who worked as a cabinet maker and carpenter on his dairy farm in Hartland, Vermont, was woodworking. Rescued from the trash, the 1970s-era guitar was refurbished by Ambros. Using a steam iron, he pried up the instrument’s wood veneer and rebuilt the front bracing of the guitar and re-anchored the strings.
Opposite:
Family is very important to Ambros and Lee. Here they are joined by their son, daughter-in-law and grandchildren, at the UMass Club in Boston on the day of the Nobel announcement.
“It’s almost therapeutic,” explained Ambros when asked why he builds guitars when he doesn’t play. “In the lab we’re always working with these tiny amounts of liquid and microscopic worms. Building a guitar is a much more macro endeavor.”
Like working at the bench, however, building a guitar involves stripping the instrument down to what really matters: the bracing, how the strings are anchored and the tension in the strings.
“You really have to envision in your head how these things come together and work,” said Ambros. Not unlike genetics.
And like lab work, “you have to try different things before you find something that might work,” said Ambros. “Ultimately, everybody who builds guitars thinks they’re going to invent something new or come up with some innovative bracing scheme that the folks at Martin [the well-known guitar-making company] never thought of and it’s going to be magically better than anything else. But that’s not likely to happen.”
Maybe not, but in the case of the discovery of microRNA, for Ambros and Lee, that’s exactly what happened. •
curiosity A culture of
RNA Therapeutics Institute fosters creativity leading to biomedical breakthroughs
By Susan E.W. Spencer
Before the roll out of COVID-19 vaccines, many people were not familiar with RNA, much less messenger RNA that powered the pandemic-ending shots.
But today, many RNA-based therapies are in clinical trials for debilitating diseases such as Huntington’s, Parkinson’s and preeclampsia.
Much of the research that spawned these potentially lifesaving treatments grew out of work done by scientists at UMass Chan Medical School’s RNA Therapeutics Institute (RTI).
So how did a young institute in Central Massachusetts, at a relatively young medical school, become a global hub of RNA research, with two of its four founding co-directors being Nobel laureates?
“What’s unique about this place is not that we hired a bunch of RNA people. It’s that we hired people into an environment that was a microcosm of the larger UMass Chan ethos,” said Phillip D. Zamore, PhD, Howard Hughes Medical Institute Investigator, the Gretchen Stone Cook Chair in Biomedical Sciences, and chair and professor of RNA therapeutics.
“That can’t be replicated without having the right culture and the investment in bringing people together.”
The stellar scientists who formed the RTI established it as a place that combined basic research and translation of scientific discoveries into medical therapies in a way not seen at other institutions, according to Dr. Zamore. The core of the RTI’s success stems from having faculty, postdoctoral researchers and students collaborate and inspire each other, leading to unexpected discoveries that can shape the future of a field.
“It wasn’t serendipity, and it wasn’t by design. It is, I think, one of the small number of possibilities that can happen when you hire smart people into environments with too little money,” said Zamore. “Once individuals can do everything they want alone, what is the incentive to collaborate?”
Since its early days, the RTI and UMass Chan have grown to attract a large amount of federal funding, private grants and philanthropy. The institution now ranks near the top among public medical schools in the Northeast in funding awarded by the National Institutes of Health.
While resources have expanded, Zamore and others in the department said the culture thrives because it is so valued.
RNA
founding
Therapeutics Institute
co-directors Phil Zamore, PhD, Craig Mello, PhD, Victor Ambros, PhD, and Melissa , Moore, PhD.
“It was RNA nirvana,” said Melissa J. Moore, PhD, professor of RNA therapeutics and former co-director of the RTI. “Not only did you have this incredible strength in RNA, but this incredibly collaborative culture. A lot of that, I think, came out of the fact that we were a relatively new kid on the block. People paid attention to the larger medical schools, and so we needed to work together to stay on top.”
Dr. Moore, who was a Howard Hughes Medical Institute Investigator, joined UMass Chan in 2007 and left full-time academic life in 2016 to become chief scientific officer at Moderna, producer of one of the first COVID vaccines. She is now retired but consults with biopharmaceutical companies making RNA therapies.
Genesis of the RTI
UMass Chan’s growth in RNA biology and therapeutics took off after Craig C. Mello, PhD, the Blais University Chair in Molecular Medicine, was awarded the 2006 Nobel Prize in Physiology or Medicine for his pioneering research on RNA interference (RNAi), in collaboration with Andrew Fire, PhD, of Stanford University.
In addition to recognizing the broad implications of RNAi for the treatment of diseases, the award brought significant investment by the state into its public medical school, including funding for the Albert C. Sherman Center.
The focus on expanding RNA biology and development of therapeutics became a centerpiece of UMass Chan’s new administration, after Terence R. Flotte, MD, the Celia and Isaac Haidak Professor, executive deputy chancellor, provost and dean of the T.H. Chan School of Medicine, came to the Medical School in 2007, the same year Michael F. Collins, MD, professor of population & quantitative health sciences and medicine, was named chancellor.
“People paid attention to the larger medical schools, and so we needed to work together to stay on top.”
Melissa J. Moore, PhD Professor of RNA therapeutics
The RTI, officially launched in 2009, was led by four co-directors who rotated duties: Zamore, Mello, Moore and Victor R. Ambros, PhD, who also came to UMass Chan in 2007. Dr. Ambros, the Silverman Chair in Natural Sciences and professor of molecular medicine, was awarded the 2024 Nobel Prize in Physiology or Medicine for his co-discovery of microRNA with Gary Ruvkun, PhD, of Harvard Medical School.
According to Moore, the institute’s initial name was the RNAi Therapeutics Institute. She pushed to drop the ‘i’ because investigators were exploring a wider range of RNA mechanisms, all which control gene expression. In addition to the small RNAi (siRNA), there were microRNA, which Drs. Ambros and Ruvkun discovered, and mRNA, which contain the blueprint for proteins.
“You can think of them as yin and yang,” Moore said. “Messenger RNA therapeutics enable us to tell the body to make more of a certain protein or new protein, whereas siRNAs and microRNAs tell the body to make less of a particular protein.”
Central to the ethos of the RTI is the shared conviction that both basic science and translational research are vital in developing effective medicines.
“There’s still a lot of unexplored stuff in the RNA field that we don’t understand,” said Moore. “It’s extremely important to continue basic curiosity-driven research, like, just how does this work? Once we have that basic knowledge, we can engineer things to make medicine.”
A Nobel breakthrough
When Mello was recruited to UMass Chan in 1993 to be part of the Cancer Center, he said he “took a chance and never looked back.”
It was here that Mello, working with C. elegans in what he described as the Medical School’s first worm lab, discovered with Dr. Fire RNAi-gene silencing by double-stranded RNA, leading to the Nobel Prize. His lab’s work also linked directly to Ambros’ and Ruvkun’s work on microRNA pathways in C. elegans, showing they were genetically and biochemically related.
“The excitement at the time was that we might be able to make drugs where we could essentially artificially program the system,” said Mello. “You could easily imagine a therapeutic where you design it to inactivate a gene that causes pathology in a human.”
With Zamore having joined the small but preeminent cadre of RNA scientists at UMass Chan in 1999 and the catalyst of a 10-year, $1 billion statewide commitment from Gov. Deval Patrick’s Life Sciences Initiative following Mello’s Nobel award in 2006, Mello said they wanted to build on the existing RNA expertise and recruit others to create the RNA Therapeutics Institute. High on the list of recruits were Ambros and Moore.
“Speaking for myself, I certainly felt like a charlatan, because of course there were no RNA therapeutics at all at that time,” Mello said.
Mello credited UMass Chan’s leadership, along with scientific expertise and culture, with helping to make the dream of RNA therapeutics a reality. They brought together genomics, genetics, systems biology, bioinformatics and gene therapy researchers into one building so they could mix together.
RNATx Symposium highlights research from concept to clinic
RNATx Symposium, the annual conference hosted by UMass Chan’s RNA Therapeutics Institute, is the place to be in late June for the who’s who of RNA therapeutics.
Since its launch in 2018, the symposium has drawn nearly 4,000 scientists, industry representatives, journalists, business developers and others. One hundred twenty-one speakers have presented, with participants coming from 272 biotechnology and pharmaceutical companies and 275 academic institutions, representing 45 countries.
“Our keynotes each year have really moved the needle in some form or fashion within the RNA field,” said Angela F. Messmer-Blust, PhD, associate professor of RNA therapeutics, senior scientific advisor and co-organizer of RNATx.
Last year, Jennifer A. Doudna, PhD, who shared the Nobel Prize in Chemistry in 2020 with Emmanuelle Charpentier, PhD, for their pioneering work using CRISPR/Cas9 gene editing, was a keynote speaker.
Other featured Nobel laureates have included UMass Chan’s Craig C. Mello, PhD, the Blais University Chair in Molecular Medicine and distinguished professor of RNA therapeutics; and Victor R. Ambros, PhD, the Silverman Chair in Natural Sciences and professor of molecular medicine, who spoke along with his Nobel co-recipient, Gary B. Ruvkun, PhD, of Harvard Medical School. Katalin Karikó, PhD, from Szeged University in Hungary, and Phillip Sharp, PhD, of Massachusetts Institute of Technology, also presented keynotes.
Keynote speakers at this year’s RNATx, to be held June 25-27, are V. Narry Kim, PhD, founding director of the Center for RNA Research, Institute for Basic Science at Seoul National University in South Korea; and Muthiah (Mano) Manoharan, PhD, senior vice president of drug innovation and distinguished research scientist at Alnylam Pharmaceuticals.
“We invite scientists from industry and academia because one of the hopes of our conference is forging new collaborations and ultimately accelerating RNA research,” said Dr. Messmer-Blust. “It is necessary for basic research to lay the groundwork for therapeutic development, and we are beginning to see this currently come to fruition with RNA therapeutics.”
PHOTO: FAITH NINIVAGGI
“I guess you can say we built on our strengths, but we didn’t just build on them, we created synergy,” said Mello. “Somehow we have been able to encourage that intermixing, that synergy, that’s made it great.”
Expanding RTI’s reach
In 2009, Andrei A. Korostelev, PhD was wrapping up his postdoctoral work at University of California Santa Cruz, focusing on translation mechanisms of ribosomes, which are responsible for decoding genetic information and synthesizing proteins in all living organisms. He saw an advertisement for the new RNA Therapeutics Institute forming at UMass Chan, with four co-directors—Mello, Zamore, Ambros and Moore—all luminaries in the field.
“When I realized that these four people are actually in the same place, I thought I should look it up,” said Dr. Korostelev, now professor of RNA therapeutics, who became the RTI’s first hired principal investigator.
“I thought that it was going to be somewhat intimidating for me to meet all these people, but instead, it immediately felt that I belong here, because it was all about science, it was all about excitement, and it felt like this is the place where the next big things are going to happen,” he said.
“I had several interviews at other places, so I remember vividly how I called my wife in the evening after the RTI interview and said this is something special.”
The support from UMass Chan administrators was also praised by Korostelev, who pointed out that it was after listening to investigators that the Medical School became the first research institution in New England to set up a highresolution electron microscope, a costly but crucial piece of equipment for zooming in on the atomic structures of cellular molecules.
Korostelev said that although the department is a therapeutics institute, he was always encouraged to work on his basic science. And in so doing, he has developed interesting ideas about therapeutics that he believes wouldn’t have happened elsewhere. He recently published one of those approaches that has the potential to treat several hundred diseases.
“I like to say that when I interviewed and when I arrived, I suspected that it’s too good to be true,” Korostelev said of the RTI. “I thought that there must be some skeletons in the closet that I will probably discover. So, it’s been 14 years and I’m still looking.”
Lessons in chemistry
By 2011, with burgeoning developments coming out of the RTI, the directors were looking to add someone with expertise in translating technical scientific ideas into drugs. Anastasia Khvorova, PhD, had previously collaborated with several of the RTI’s senior investigators while working in the biotechnology field. She was recruited to UMass Chan to start the Nucleic Acid Chemistry Center, the only nonprofit facility in North America capable of gram-scale synthesis of modified oligonucleotides.
“If you want to be serious about RNA therapeutics, you have to be able to make it correctly,” said Dr. Khvorova, the Remondi Family Chair in Biomedical Research and professor of RNA therapeutics. “The process for making RNA or DNA or oligonucleotides requires a lot of chemical engineering and a lot of equipment.”
Khvorova continues to collaborate with colleagues on bringing RNA therapeutics to clinical trials, co-founding or serving as an advisor to several biotech companies. Among the companies that grew out of research from the RTI are Comanche Biopharma, maker of an RNA therapeutic for preeclampsia; Atalanta Therapeutics, deploying RNAi to treat neurodegenerative diseases; and Alys Pharmaceuticals, which aims to redefine therapy for immune-dermatology conditions such as vitiligo and alopecia areata.
These companies build on earlier biotech developments from the RTI, notably Alnylam Pharmaceuticals, co-founded in 2002 by Zamore. In 2018, Alnylam announced the firstever FDA approval of an RNAi therapeutic for the treatment of a rare, inherited, rapidly progressive and life-threatening adult disease with a constellation of manifestations.
“Chemistry is essential,” said Khvorova. And by chemistry, she means not only the scientific field, but also the interconnection between people and the community.
“You have a list of faculty here in which each one of them is a star, and they can have labs anywhere they want, but they choose to be here,” she said. “It’s clearly a chemistry between faculty, but it’s also continuous support from the dean and chancellor, and we are very lucky with Phil (Zamore) as department chair. He has enormous charisma, and he cares, and I think that really matters.”
The RTI’s success has contributed greatly to the success of UMass Chan, according to Khvorova; and success of the Medical School profoundly contributed to the birth of the biotech industry in Worcester and the region’s overall economic development.
Engineering the future
The RTI isn’t finished growing yet.
Zamore highlighted his vision for the future, which would include rolling out a graduate program in RNA biology and a service requirement for graduate students, such as Science Learning with Interactive Virtual Education (ScienceLIVE), an online education outreach program for middle school-age students developed by the RTI. “Just like medical students, they have to engage with civil society, not just be tied to the lab,” he said.
The department is searching for its first Maraganore Early Independence Fellow, an exceptionally talented junior scientist who will develop an independent research program in RNA biology or RNA therapeutics.
Finding new sources of funding is a challenge for a lab that is beyond the start-up stage and faces deeper competition. Zamore said the department may have to re-envision how they structure resources.
“I have amazing colleagues. I’ve been here for 25 years because I’ve never had any desire to leave, and I feel very committed to helping ensure that we retain the things that are wonderful and that we fix the things that aren’t,” said Zamore.
Another aspect of the RTI is still ascending: “We’re definitely on the map. A lot of the world is paying attention to what’s happening here,” said Mello. “I don’t think the Nobel Committee is done with us yet.” •
“A lot of the world is paying attention to what’s happening here. I don’t think the Nobel Committee is done with us yet.”
Craig C. Mello, PhD Blais University Chair in Molecular Medicine
PHOTO:
Nurturing the next generation of scientists
Nobel laureate Victor Ambros, PhD, inspires mentees worldwide through enthusiasm, curiosity and trust
By Hallie Leo
When Victor R. Ambros, PhD, received the 2024 Nobel Prize in Physiology or Medicine for co-discovering microRNA, mentees around the globe from China to Chicago celebrated, recounting their fondest memories with the ultra-charismatic scientist.
UMass Chan Distinguished Professor and Nobel laureate Craig C. Mello, PhD, who completed his doctoral research in Ambros’ lab at Harvard University, remembers playing volleyball on Friday evenings in Cambridge in 1984 and sipping beer from a hollowed-out ball with Dr. Ambros, the Silverman Chair in Natural Sciences and professor of molecular medicine. A nod to their friendship exists on UMass Chan’s campus via a sand volleyball court that Dr. Mello helped install.
“Victor inspires me through his enthusiasm for science and the curiosity he displays,” said Mello, the 2006 corecipient of the Nobel Prize in Physiology or Medicine for co-discovering RNAi. “He’s got a phenotype similar to mine where we’re on the same page, easily excited and feeding each other’s enthusiasm.”
“Victor plays at the science. For him, it’s fun, and he makes it fun for others. That’s why he’s good at what he does,” Mello said. “He’s a Nobel magnet. He says it’s because he was in the right room. I told him, ‘Victor, you made it the right room.’”
Zhongchi Liu, PhD, met Dr. Ambros and Mello in 1984 as a PhD student entering the Cell and Developmental Biology Department at Harvard University. Dr. Liu, who fondly remembers having tea time many afternoons
while a student, coincidentally discovered Ambros had won the Nobel Prize while she was jogging near a tea house.
“When I came to the U.S. in the early 80s, I never tasted Coke, had a credit card or a phone. There was a lot I didn't know,” said Liu. “My confidence was low and Victor encouraged me by simply being kind and using an equal-footing attitude to talk to me. It made a difference in my self-confidence and my growth as a scientist.”
In the Ambros lab, Liu studied genes in C. elegans, focusing on a special form of worm—the dauer larva— that seals its mouth to avoid eating. Her research found how the heterochronic genes regulated the timing of development. She is currently a distinguished professor at the Shenzhen University of Advanced Technology, in Shenzhen, China, after working as a professor at the University of Maryland for 28 years.
In 2009, Ambros and his wife, Rosalind “Candy” Lee, the senior scientist and first author on the 1993 Cell paper cited by the Nobel Committee, visited China with Liu to see the total solar eclipse. When they arrived, a Shanghai Medical College student picked them up and started talking about his own project on microRNA, unaware he was transporting the scientists who discovered it.
“Victor was smiling because he didn’t tell the student that he discovered microRNA, and somehow the student didn’t know,” said Liu. “It was funny that Victor didn’t point it out. He’s very low key.”
During that trip, Liu confided that she was switching her field of research from arabidopsis to wild strawberry, aiming to redomesticate strawberries for vertical farming, hoping for an environmentally sustainable way to grow horticulture crops and increase the strawberry’s nutritional value.
“Although I switched from worms to arabidopsis and then to wild strawberry, I applied the same genetic approaches, which I owe a lot to Victor’s training,” Liu said. “I treat strawberries like C. elegans, doing gene knockouts and looking at the phenotype. I learned to think like Victor in asking important biological questions.”
Howard Scott Silverman, DPhil, founder and CEO of the entrepreneurial investment firm Agman, which launches companies and builds them into enterprises, was a freshman at Dartmouth College in an introductory biology class when he met Ambros. His research focused on transcriptional regulation of lin-4, the original microRNA discovered by the Ambros lab.
Victor had won the Nobel Prize when I read a text from my father in all caps, ‘YOU WERE RIGHT!’”
Silverman and Ambros have gathered biannually over the past 30 years, skiing in Colorado or grabbing dinner in Chicago or Boston. The Nobel laureate even coached Silverman, a then grad student at Oxford University, through his first marathon in 2000, the London Marathon.
“Victor plays at the science. For him, it’s fun, and he makes it fun for others. That’s why he’s good at what he does.”
— CRAIG C. MELLO, P h D
“The thrill of science and of discovery was invigorating for me,” said Dr. Silverman. “Victor elevates my thinking every time I’m around him.”
Ambros proudly bears the name of his mentee as the Silverman Chair in Natural Sciences, a chair endowed by Silverman and his family in 2008.
“I saw an opportunity as an investor to make a bet on something that felt like a sure thing,” Silverman said. “Our family was thrilled and privileged to endow a professorship at UMass Chan, which was based on the legacy of our relationship. I learned that
When Sungwook Choi, PhD’18, met his mentor in Worcester, he was surprised that the scientist who discovered microRNA was so easy to talk to and would throw birthday parties for everyone in the lab.
Dr. Choi, who grew up in Seoul and moved to the U.S. to attend UMass Chan, dubbed Ambros and Lee his “U.S. father and mother,” recalling them as the first visitors at his bedside when he was in the emergency room with kidney stones.
In the Ambros lab, Choi focused on researching developmental genetics, analyzing a mutation in C. elegans of the lin-28 protein, and discovering that the mutation is related to development feedback in reproductive organs.
“Victor said the best experimental design is one that can disprove my hypothesis. He always tries not to form a bias when looking at a phenomenon. My thinking skills evolved with him,” said Choi, a principal scientist at HanAll Biopharma, in South Korea. “He’s an inspiring scientist and a motivational and supportive mentor.”
Samantha “Sam” Burke, PhD’15, remembers her mentor blasting Bruce Springsteen in the lab. Dr. Burke met Ambros at an accepted student reception at UMass Chan, striking up a conversation about their shared alma mater, the Massachusetts Institute of Technology. She later joined his lab.
“I always appreciated Victor’s genuine kindness,” said Burke. “When you have a conversation with him, it’s clear that he cares, wants to get to know you and hear your opinions. I never doubted that he believed in me, or that he thought I was smart.”
Burke’s work in the Ambros lab focused on two microRNAs in C. elegans that are also present in humans. She discovered that the pair work together to ensure that cells in the worm’s reproductive system migrate properly when the worm experiences environmental temperature changes.
“I appreciate how much Victor values all roles in science. He’s grateful for his education, his father’s education and the role that school teachers had on both of them,” said Burke, a ninth grade science and senior research elective teacher at Noble and Greenough School in Dedham. “When I said I wanted to be a teacher, he thought it was the greatest thing in the world and was excited for me to inspire students to explore science.”
“I try to bring his positivity to everything I do,” continued Burke, who was recently diagnosed with osteosarcoma, originating in her sacrum and metastasizing to her lungs. Her mentor’s philosophy extends to her approach to chemotherapy and treatment. “Victor always modeled that we need to keep trying, stay on task and not give up when things get hard. His positivity and advice of always chipping away at things is something I’ll carry with me.”
Congratulations to your new medicine laureates!
The Nobel Prize Stockholm
So well deserved! I’m so proud that I had the chance to work with and learn from Victor!
Isana Veksler-Lublinsky Israel
Congratulations Dr. Ambros!! Such wonderful and touching news. I still remember when I met you at UMass! Keep making a difference in this world!
Elena Merino Rodriguez, PhD The Netherlands
It was an absolute privilege and luck to have been able to learn and work with Victor Ambros and Rosalind Lee’s wonderful team in my time as a PhD student at UMass Chan Medical School. It was the cherry on top of the cake that was the incredibly rich scientific environment I found on that campus!
Daniel Chavez, PhD London
It's wonderful to see such groundbreaking research in medicine being recognized. The discovery of microRNA has the potential to advance our understanding of genetics significantly.
Anton Mintin Moscow
As I was reading about the 2024 Nobel Prize winners in Medicine, I couldn’t help but be inspired by Victor Ambros and Gary Ruvkun. . . Their journey, from being doubted to changing the field of genetics, shows the power of persistence, collaboration, and curiosity.
Manish Kumar, PhD Germany
Most of my research career involved using therapeutic lentiviral vectors at the City of Hope under John Rossi, John Zaia, and David DiGiusto that used miRNA and shRNA cassettes developed based on some of Dr. Ambros and Ruvkun’s discoveries. What a time to be an RNA biologist.
Elizabeth Epps, PhD
San Mateo
How thrilling!
Beth Graff Fischer Farmington
Congrats! What an exciting time for the whole UMass Chan community. I remember the day I was introduced to Dr. Ambros, I was told he would win the Nobel Prize someday.
Keri Kirrane
Dallas-Fort Worth
Congratulations from around the globe
Below is a sampling of the hundreds of congratulatory notes from around the world posted in response to the Nobel Prize announcement on Oct. 7, 2024.
Compiled by Colleen Locke
Congratulations to Lasker laureates Victor Ambros and Gary Ruvkun, who have been awarded the 2024 Nobel Prize in physiology or medicine!
Lasker Foundation
New York City
Today’s announcement about the Nobel Prize in Medicine highlights the importance and impact of basic research!
Victor Ambros and Gary Ruvkun’s research slowly changed our understanding of ALL protein biology.
Nipun Chopra, PhD Indianapolis
And UMass Chan Medical School births another Nobel laureate!
Kim W. McIntyre Nashville
Today's Nobel Prize in Medicine or Physiology is built on curiosity-driven research . . . It has led to some remarkable technology spin-offs including drugs like Spinraza treating Spinal muscular atrophy. Invest in discovery science!
Mark Pfeifer
Chapel Hill
So well deserved!! Proud to be a UMass alum :)
Timothy Menz, MD, FAAP Springfield
MIT alumnus Victor Ambros ’75, PhD ’79 and Gary Ruvkun, a former MIT postdoc, have won the 2024 Nobel Prize in Physiology or Medicine for work on microRNA.
Massachusetts Institute of Technology
Cambridge
Congratulations to UMass Chan and the Program in Molecular Medicine for this amazing milestone!!!
Vida Tajiknia, MD Providence
CONGRATULATIONS
DR. AMBROS!!!! KUDOS TO UMASS CHAN FOR HAVING ITS SECOND PRIZE WINNER!!!!!!!
Marian V. Wilson Lancaster
It was such a personal delight to see Victor receive this award. One of the most open minded and kindest scientists I have ever worked with. Thanks Victor for your generosity of time and the sharing of your enthusiasm Congratulations and best wishes.
David A. Jewell, PhD
Gainesville
Congratulations to #NASmembers Victor Ambros and Gary Ruvkun on winning the 2024 #NobelPrize in Physiology or Medicine for their discovery of microRNA and its crucial role in post-transcriptional gene regulation.
National Academy of Sciences Washington, D.C.
At 2024 Convocation and Investiture, Chancellor embraces racing toward ‘ambitious future’
In his annual Convocation address in September, Chancellor Michael F. Collins celebrated the accomplishments of the UMass Chan Medical School community and kicked off the year with a rallying cry of “We are not done yet!” He called for continued teamwork, collaboration and encouragement among students, faculty and staff to fulfill the Medical School’s mission.
Chancellor Collins said the collaborative work at UMass Chan is similar to running a marathon, noting the same motivation and inspiration traded between runners to complete a race takes place here as the community advances the education,
research, sustainability, philanthropy and social mission goals of advancing diversity, equity, inclusion and belonging.
“In our work, there is no finish line, only new starting points. Let us begin this academic year by rounding the corner, arm in arm, and let us commit together to racing to our most ambitious future. There is much to accomplish,” Collins said.
The chancellor listed some of the momentous achievements of the past year that will carry UMass Chan beyond the goals included in the Impact 2025 strategic plan, including: the largest graduate school classes in UMass Chan’s history; the creation of
a new regional campus, UMass ChanLahey, and enrollment of 32 medical students in its first year; and the opening of the new education and research building.
The following faculty members were honored and invested as endowed professors at the ceremony:
• Daryl A. Bosco, PhD, professor of neurology and biochemistry & molecular biotechnology and associate vice chair of research for the Department of Neurology, was invested as the Paul J. DiMare Chair in Neurodegenerative Disease
• Kevin Donahue, MD, professor of medicine in the Division of Cardiovascular Medicine, was invested as the David J. and Barbara D. Milliken Professor of Preventive Cardiology.
• Dale L. Greiner, PhD, professor of molecular medicine and co-director of the Diabetes Center of Excellence, was invested as the Herman G. Berkman Chair in Diabetes Care Innovation.
• John E. Harris, MD, PhD’05, chair and professor of dermatology, was invested as the Lambi and Sarah Adams Chair in Genetic Research
• Elinor K. Karlsson, PhD, associate professor of molecular medicine, was invested as the Dr. Eileen L. Berman and Stanley I. Berman Foundation Chair in Biomedical Research
• Danny G. Winder, PhD, chair and professor of neurobiology, was invested as the Worcester Foundation for Biomedical Research Chair I
• Jeannette M. Wolfe, MD, professor of emergency medicine, was invested into the Joy McCann Professorship for Women in Medicine.
Opposite: In his annual Convocation address, Chancellor Collins issues a rallying cry of, “We are not done yet!,” calling for a continuation of the collaboration and teamwork that define the institution.
Clockwise from top: From left, Dean Flotte; John Harris, MD; Kevin Donahue, MD; Elinor Karlsson, PhD; Danny Winder, PhD; Jeannette Wolfe, MD; Daryl Bosco, PhD; and Chancellor Collins.
Chancellor Collins presents a medal to the DiMare family commemorating their endowment of the Paul J. DiMare Chair in Neurodegenerative Disease. Pictured from left are Daryl Bosco, PhD, Tony DiMare, Swanee DiMare and Chancellor Collins.
Dean Flotte and Chancellor Collins with Dr. Harris, center.
Left: Dean Flotte and Chancellor Collins with the newly invested Jeannette Wolfe.
All photos on this spread: John Gillooly/PEI
Special investiture ceremony celebrates newly endowed chairs
On the heels of the annual Investiture ceremony, Chancellor Michael F. Collins announced the creation of an additional 12 endowed chairs, meeting the institutional goal of 75 endowed chairs by 2025.
In recognition of exceptional faculty and the extraordinary, longstanding partnership and shared destiny of UMass Memorial Health and UMass Chan Medical School, Chancellor Collins announced that a $5 million philanthropic gift from UMass Memorial Health and $2.5 million in matching funds from the University of Massachusetts Foundation would allow UMass Chan to establish five new UMass Memorial Health endowed chairs.
Seven additional endowed chairs were established and approved by the UMass Board of Trustees.
The inaugural holders of the UMass Memorial Health chairs, who were invested at a special ceremony in November, are:
• A.M. Barrett, MD, chair and professor of neurology, was named the UMass Memorial Chair in Neurology.
• Thomas J. FitzGerald, MD’80, chair and professor of radiation oncology, was named the UMass Memorial Chair in Radiation Oncology.
• Diane McKee, MD, chair and professor of family medicine & community health, was named the UMass Memorial Ledwith Chair in Family and Community Medicine.
• Max P. Rosen, MD, MPH, chair and professor of radiology, was named the UMass Memorial Chair in Radiology.
• Matthias Walz, MD, chair and professor of anesthesiology & perioperative medicine, was named the UMass Memorial Kaur Chair in Anesthesiology and Perioperative Medicine.
Also invested at the special ceremony were the inaugural holders of three new UMass Chan endowed chairs:
• Anil Chandraker, MD, professor of medicine, was named the Jack M. Wilson Chair in Biomedical Research.
• Fernando Martinez, MD, MS, professor of medicine, was named the Joseph D. Early Chair in Biomedical Research.
Left: Thomas FitzGerald, MD; Diane McKee, MD; Matthias Walz, MD; Anil Chandraker, MD; Dorothy Schafer, PhD; Chancellor Collins; Max Rosen, MD, MPH; A.M. Barrett, MD; and Fernando Martinez, MD, MS.
Top right: Chancellor Collins presented a framed version of the UMass Memorial Health endowed chair medals to UMass Memorial Health CEO Eric Dickson, MD, and UMass Memorial Health Board of Trustees Chair Lynda Young, MD.
Lower right: Jack Wilson (left) and Chancellor Collins, with Dr. Chandraker, the newly endowed Jack M. Wilson Chair in Biomedical Research.
All photos on this page: John Gillooly/PEI
• Dorothy Schafer, PhD, associate professor of neurobiology, was named the UMass Chan Medical School Chair in Biomedical Research I
Chancellor Collins attends opening ceremony of WHO Academy
Chancellor Michael F. Collins attended the opening ceremony of the World Health Organization’s WHO Academy in December in Lyon, France. He was personally invited by World Health Organization Director-General Tedros Adhanom Ghebreyesus, PhD, during the director-general’s visit to UMass Chan Medical School in June.
The WHO Academy is an eco-friendly facility designed to encourage collaboration. It features a world-class simulation center aimed at addressing gaps in health workforce training among WHO member states, using new
technologies and advancements in adult learning.
The opening ceremony featured exhibitions and demonstrations showcasing the academy’s approach to lifelong learning.
The hybrid event was co-hosted by the WHO and the government of France, with Dr. Tedros and French President Emmanuel Macron in attendance.
Paul J. DiMare Foundation makes $35 million gift to UMass Chan
UMass Chan Medical School announced a $35 million philanthropic gift from the Paul J. DiMare Foundation to advance research at UMass Chan Medical School, to support breakthroughs in neurodegenerative and genetic diseases, especially ALS, and to recruit outstanding biomedical research faculty at all career stages. The $35 million commitment is the third largest ever received by the University of Massachusetts and will be designated entirely for the endowment.
In recognition of the generous support from the Paul J. DiMare Foundation, the new education and research building was named the Paul J. DiMare Center.
The Paul J. DiMare Foundation honors the legacy of the DiMare family patriarch, Paul J. DiMare. A
native of Belmont, Massachusetts, DiMare began working in his family’s produce business at Boston’s Haymarket Square when
he was 11 years old. With time, he led and expanded operations and distribution to become one of the country’s most inventive and influential agricultural business leaders. Today, the DiMare Company is one of the largest fresh-market tomato growers and distributors in the country. DiMare was a committed philanthropist who was involved in numerous community organizations and nonprofits until his death in 2022 at 81.
Anthony J. DiMare, Paul’s son, said the DiMare Foundation has a long-standing commitment to supporting health care and medical research and the DiMare family is “pleased to play a part in supporting UMass Chan and advancing research in neurodegenerative diseases, especially ALS.”
Right: Chancellor Collins with French President Emmanuel Macron at the WHO Academy’s opening ceremony.
Above: Paul J. DiMare
UMass Chan-Lahey welcomes first cohort of medical students
The first cohort of 32 LEAD@ Lahey medical students at the UMass Chan-Lahey regional campus in Burlington gathered in September to mark the launch of the new program, which was accredited by the New England Commission of Higher Education and the Liaison Committee on Medical Education earlier in 2024.
Students in the LEAD@Lahey (which stands for lead, empower, advocate and deliver) track follow the core curriculum of the T.H. Chan School of Medicine with additional emphasis on leadership, health systems science and interprofessional education, preparing them to lead and solve future challenges in health care. This is the second UMass Chan regional campus. The Populationbased Urban and Rural Community
Health, or PURCH, track at UMass Chan-Baystate in Springfield was established in 2017.
“This new regional campus benefits not only Burlington, but the surrounding communities,” said Chancellor Michael F. Collins. “While our initial roots are in Worcester, let me be clear that we are the state’s medical school, the commonwealth’s medical school. We are proud to now go from the Cape to the Berkshires, from Springfield to Burlington.”
Terence R. Flotte, MD, the Celia and Isaac Haidak Professor, executive deputy chancellor, provost and dean of the T.H. Chan School of Medicine, thanked the new students, saying, “Medical education is a learning experience for both the faculty and students, so we look forward to learning.”
Top: The inaugural cohort of LEAD@Lahey medical students—32 strong—gather on the UMass Chan-Lahey regional campus in Burlington.
Above: Dean Flotte welcomed the new medical students and thanked them for the opportunity for a shared learning experience.
Historic painting, ‘The First Operation Under Ether,’ now on display at UMass Chan
UMass Chan Medical School celebrated the arrival of the historical medical painting, “The First Operation Under Ether,” by American artist Robert C. Hinckley.
The original work of art, on longterm loan from the Boston Medical Library, is on display in the Lamar Soutter Library.
From 1882 to 1893, Hinckley researched and painted his interpretation of the first successful public demonstration of ether anesthesia, which occurred Oct. 16, 1846, at Massachusetts General Hospital. This historic event is considered the beginning of modern anesthesia.
The artwork depicts John Collins Warren, a surgeon at Massachusetts General Hospital, removing a tumor from the neck of his patient Gilbert Abbott. The ether was administered to Abbott by dentist William Morton, who just weeks
before had performed a successful tooth extraction using ether. The surgery took place in the operating theater in the Bulfinch Building at Massachusetts General Hospital, now known as the Ether Dome.
Above: The historic painting “The First Operation Under Ether,” by Robert C. Hinckley, is installed in the Lamar Soutter Library in January. It is on long-term loan from Boston Medical Library.
Alumni Distinguished Service Award
Every year at reunion, the UMass Chan Medical School Alumni Association presents the Alumni Distinguished Service Award, a prestigious recognition of alumni, by alumni, for alumni.
The award honors an alumnus/a who has made a significant impact in their field, showcases UMass Chan and serves as an inspiration for current students. The Alumni Association seeks to recognize an alumnus with outstanding career achievements that embody the UMass Chan mission, vision and values.
Now is your chance to honor a fellow alum— someone who mentored you in your residency, inspired you with their research or made extraordinary contributions through a unique career path—by nominating them for the 2026 Alumni Distinguished Service Award.
To learn more about the award criteria or nominate a fellow alum, visit the UMass Chan Alumni Association website.
PHOTO: PHIL SMITH
Chancellor Collins speaks at a campus
During a special event at the National Academy of Sciences celebrating the 2024 class of Nobel laureates from America, I caught a glimpse of our newest Nobel laureate, Victor R. Ambros, PhD, who, at that moment, appeared to be deep in thought.
When the program concluded, I walked over to Victor and inquired what was on his mind. Could it have been a recognition of how much his life had changed since the Nobel announcement?
I was surprised to hear that he was not reflecting on his newfound celebrity status but on how much he would have liked his parents to be by his side, to marvel in this exceptionally rare and incredibly momentous occasion with him.
Several weeks earlier, just hours after the Oct. 7 early morning announcement of the 2024 Nobel Prize in Physiology or Medicine was announced in Stockholm, Sweden, Victor took part in a press conference on campus. Standing at a podium and taking in the overflowing crowd of media, colleagues and well-wishers, he reflected on the path that led to this auspicious moment saying, “I am the son of an immigrant from Poland . . . [who] was captured by the Nazis. He worked as a slave laborer, in a factory for a few years.” Eventually, his father was liberated and “befriended some people in the occupying U.S. Army, one of whom became his very close friend and sponsored his immigration to the States. And so that’s how I’m here.”
While there is one UMass Chan, as Victor’s personal story so vividly illustrates, there are many paths that lead to our campus. In these pages, you have read how our newest Nobel laureate has made the most of his UMass Chan experience, and we feel so fortunate to have him as a cherished colleague, mentor, contributor and champion for our medical school. As he added during his Nobel press conference, “This is a great state university, and I wish everyone who lived in this state knew how they can take proud ownership in what happens here.”
Thanks to Victor’s Nobel moment, more people are taking ownership of our state’s worldclass medical school. A case in point is the Paul J. DiMare Foundation of Homestead, Florida, which recently made a $35 million gift to support the pioneering neurodegenerative research taking place in our new education and research building, where Victor’s lab is located. Now, more than ever, the support and investment of individuals, families and foundations are critical to sustaining UMass Chan’s mission and the work of preeminent faculty members like Victor for years to come.
Michael F. Collins, MD Chancellor and Senior Vice President for the Health Sciences
celebration of the Nobel Prize in October. He shares the stage with Craig Mello, PhD, Victor Ambros, PhD, and Rosalind “Candy” Lee.
PHOTO: FAITH NINIVAGGI
@umasschan
@umasschan is the magazine of UMass Chan Medical School, one of five campuses of the UMass system. The magazine is distributed periodically to members, benefactors and friends of the UMass Chan community. It is produced and published by the Office of Communications.
Readers are invited to comment on the contents of the magazine, via email to UMassChanCommunications@umassmed.edu; please include “@umasschan magazine” in the subject line.
Chancellor and Senior Vice President for the Health Sciences: Michael F. Collins, MD
Executive Deputy Chancellor, Provost and Dean of the T.H. Chan School of Medicine: Terence R. Flotte, MD
Executive Vice Chancellor for Communications: Jennifer Berryman
Associate Vice Chancellor for Communications: Lisa L. Larson
Editor: Ellie Castano
Design: Dan Lambert
Office of Communications staff contributors: Samuella Akaab, Joanna Alizio, Andries Hannaart, Jim Fessenden, Rey Gonzalez, Bryan Goodchild, Hallie Leo, Colleen Locke, Hayley Mignacca, Pat Sargent, Susan E.W. Spencer, Sarah Willey
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Listen to the podcast today:
UMass Chan Medical School has launched Rare Diseases, Real Stories, a six-episode podcast series that shines a spotlight on the courage, resilience and advocacy work of families affected by rare diseases.
Each episode offers an intimate look into their lives, struggles with grief, determination to fight for answers and their profound love and hope. The series illuminates the incredible network of scientists, clinicians, families and advocates working to drive rare diseases research forward.
The podcast is produced by the Office of Communications at UMass Chan and available on all major streaming platforms. www.umassmed.edu/rarediseasesrealstories
