Category: Faculty Locations

W.M. Keck Foundation to support research on healthy aging at MIT

Assistant Professor of Biology Alison Ringel will investigate the intersection of immunology and aging biology, aiming to define the mechanisms that underlie aging-related decline, thanks to grant from prestigious foundation.

Lillian Eden | Department of Biology
October 9, 2025

A prestigious grant from the W.M. Keck Foundation to Assistant Professor of Biology Alison Ringel will support groundbreaking healthy aging research at MIT.

Ringel, also a Core Member of the Ragon Institute, will draw on her background in cancer immunology to create a more comprehensive biomedical understanding of the cause and possible treatments for aging-related decline.

“It is such an honor to receive this grant,” Ringel says. “This support will enable us to draw new connections between immunology and aging biology. As the U.S. population grows older, advancing this research is increasingly important, and this line of inquiry is only possible because of the W.M. Keck Foundation.”

Understanding how to extend healthy years of life is a fundamental question of biomedical research with wide-ranging societal implications. Although modern science and medicine have greatly expanded global life expectancy, it remains unclear why everyone ages differently; some maintain physical and cognitive fitness well into old age, while others become debilitatingly frail later in life.

Our immune systems are adaptable, but they do naturally decline as we get older. One critical component of our immune system is CD8+ T cells, which are known to target and destroy cancerous or damaged cells. As we age, our tissues accumulate cells that can no longer divide. These senescent cells are present throughout our lives, but reach seemingly harmful levels as a normal part of aging, causing tissue damage and diminished resilience under stress.

There is now compelling evidence that the immune system plays a more active role in aging than previously thought.

“Decades of research have revealed that T cells can eliminate cancer cells, and studies of how they do so have led directly to the development of cancer immunotherapy,” Ringel says. “Building on these discoveries, we can now ask what roles T cells play in normal aging, where the accumulation of senescent cells, which are remarkably similar to cancer cells in some respects, may cause health problems later in life.”

In animal models, reconstituting elements of a young immune system has been shown to improve age-related decline, potentially due to CD8+ T cells selectively eliminating senescent cells. CD8+ T cells progressively losing the ability to cull senescent cells could explain some age-related pathology.

Ringel aims to build models for the express purpose of tracking and manipulating T cells in the context of aging and to evaluate how T cell behavior changes over a lifespan.

“By defining the protective processes that slow aging when we are young and healthy, and defining how these go awry in older adults, our goal is to generate knowledge that can be applied to extend healthy years of life,” Ringel says. “I’m really excited about where this research can take us.”

The W. M. Keck Foundation was established in 1954 in Los Angeles by William Myron Keck, founder of The Superior Oil Company. One of the nation’s largest philanthropic organizations, the W. M. Keck Foundation supports outstanding science, engineering and medical research. The Foundation also supports undergraduate education and maintains a program within Southern California to support arts and culture, education, health and community service projects.

Alnylam Pharmaceuticals establishes named fund in honor of co-founder

The Phil Sharp-Alnylam Fund for Emerging Scientists will support graduate students and faculty in MIT Biology.

Lillian Eden | Department of Biology
October 8, 2025

It’s no question that graduate school in fundamental research was never for the faint of heart, but academia’s nationwide funding disruptions threaten not just research happening now, but the critical pipeline for the next generation of scientists.

“What’s keeping me up at night is the uncertainty,” says Nobel Laureate Phillip A. Sharp, Institute Professor and Professor of Biology Emeritus, and Intramural Faculty at the Koch Institute.

In the short term, Sharp foresees challenges in sustaining students so they can complete their degrees, postdoctoral scholars to finish their professional preparation, and faculty to set up and sustain their labs. In the long term, the impact becomes potentially existential — fewer people pursuing academia now means fewer advancements in the decades to come.

So, when Sharp was looped into discussions about a gift in his honor, he knew exactly where it should be directed. Established this year thanks to a generous donation from Alnylam Pharmaceuticals, the Phil Sharp-Alnylam Fund for Emerging Scientists will support graduate students and faculty within life sciences.

“This generosity by Alnylam provides an opportunity to bridge the uncertainty and ideally create the environment where students and others will feel that it’s possible to do science and have a career,” Sharp says. 

The fund is set up to be flexible, so the expendable gift can be used to address the evolving needs of the Department of Biology, including financial support, research grants, and seed funding. 

“This fund will help us fortify the department’s capacity to train new generations of life science innovators and leaders,” says Amy E. Keating, Department Head and Jay A. Stein (1968) Professor of Biology and Professor of Biological Engineering. “It is a great privilege for the department to be part of this recognition of Phil’s key role at Alnylam.”

Alnylam Pharmaceuticals, a company Sharp cofounded in 2002, is, in fact, a case study for the type of long-term investment in fundamental discovery that leads to paradigm-shifting strides in biomedical science, such as: what if the genetic drivers of diseases could be silenced by harnessing a naturally occurring gene regulation process? 

Good things take time

In 1998, Andrew Fire, PhD ’83, who was trained as a graduate student in the Sharp Lab at MIT, and Craig Mello published a paper showing that double-stranded RNA suppresses the expression of the protein from the gene that encodes its sequence. The process, known as RNA interference, was such a groundbreaking revelation that Fire and Mello shared a Nobel Prize in Medicine and Physiology less than a decade later. 

Four of the five cofounders of Alnylam Pharmaceuticals: (from left to right) Tom Tuschl, Phil Sharp, David Bartel, and Phil Zamore. Not pictured: Paul Schimmel. Photo credit: Christoph Westphal

RNAi is an innate cellular gene regulation process that can, for example, assist cells in defending against viruses by degrading viral RNA, thereby interfering with the production of viral proteins. Taking advantage of this natural process to fine-tune the expression of genes that encode specific proteins was a promising option for disease treatment, as many diseases are caused by the creation or buildup of mutated or faulty proteins. This approach would address the root cause of the disease, rather than its downstream symptoms.

The details of the biochemistry of RNAi were characterized and patented, and in 2002, Alnylam was founded by Sharp, David Bartel, Paul Schimmel, Thomas Tuschl, and Phillip Zamore. 

“16 years later, we got our first approval for a totally novel therapeutic agent to treat disease,” Sharp says. “Something in a research laboratory, translated in about as short a time as you can do, gave rise to this whole new way of treating critical diseases.” 

This timeline isn’t atypical. Particularly in healthcare, Sharp notes, investments often occur five or ten years before they come to fruition. 

“Phil Sharp’s visionary idea of harnessing RNAi to treat disease brought brilliant people together to pioneer this new class of medicines. RNAi therapeutics would not exist without the bridge Phil built between academia and industry. Now there are six approved Alnylam-discovered RNAi therapeutics, and we are exploring potential treatments for a range of rare and prevalent diseases to improve the lives of many more patients in need,” says Kevin Fitzgerald, Chief Scientific Officer of Alnylam Pharmaceuticals. 

Today, the company has grown to over 2,500 employees, markets its six approved treatments worldwide, and has a long list of research programs that are likely to yield new therapeutic agents in the years to come. 

Change is always on the horizon

Sharp foresees potential benefits for companies investing in academia, in the way Alnylam Pharmaceuticals has through the Phil Sharp-Alnylam Fund for Emerging Scientists. 

“We are proud to support the MIT Department of Biology because investments in both early-stage and high-risk research have the potential to unlock the next wave of medical breakthroughs to help so many patients waiting for hope throughout the world,” says Yvonne Greenstreet, Chief Executive Officer of Alnylam Pharmaceuticals. 

It is prudent for industry to keep its finger on the pulse — for becoming aware of new talent and for anticipating landscape-shifting advancements, such as Artificial Intelligence. Sharp notes that academia, in its pursuit of fundamental knowledge, “creates new ideas, new opportunities, and new ways of doing things.” 

“All of society, including biotech, is anticipating that AI is going to be a great accelerator,” Sharp says. “Being associated with institutions that have great biology, chemistry, neuroscience, engineering, and computational innovation is how you sort through this anticipation of what the future is going to be.” 

But, Sharp says, it’s a two-way street: academia should also be asking how it can best support the future workplaces for their students who will go on to have careers in industry. To that end, the Department of Biology recently launched a career connections initiative for current trainees to draw on the guidance and experience of alums, and to learn how to hone their knowledge so that they are a value-add to industry’s needs.  

“The symbiotic nature of these relationships is healthy for the country, and for society, all the way from basic research through innovative companies of all sizes, healthcare delivery, hospitals, and right down to primary care physicians meeting one-on-one with patients,” Sharp says. “We’re all part of that, and unless all parts of it remain healthy and appreciated, it will bode poorly for the future of the country’s economy and well-being.”

A cysteine-rich diet may promote regeneration of the intestinal lining, study suggests

The findings from the Yilmaz Lab recently published in Nature, may offer a new way to help heal tissue damage from radiation or chemotherapy treatment.

Anne Trafton | MIT News
October 1, 2025

A diet rich in the amino acid cysteine may have rejuvenating effects in the small intestine, according to a new study from MIT. This amino acid, the researchers discovered, can turn on an immune signaling pathway that helps stem cells to regrow new intestinal tissue.

This enhanced regeneration may help to heal injuries from radiation, which often occur in patients undergoing radiation therapy for cancer. The research was conducted in mice, but if future research shows similar results in humans, then delivering elevated quantities of cysteine, through diet or supplements, could offer a new strategy to help damaged tissue heal faster, the researchers say.

“The study suggests that if we give these patients a cysteine-rich diet or cysteine supplementation, perhaps we can dampen some of the chemotherapy or radiation-induced injury,” says Omer Yilmaz, director of the MIT Stem Cell Initiative, an associate professor of biology at MIT, and a member of MIT’s Koch Institute for Integrative Cancer Research. “The beauty here is we’re not using a synthetic molecule; we’re exploiting a natural dietary compound.”

While previous research has shown that certain types of diets, including low-calorie diets, can enhance intestinal stem cell activity, the new study is the first to identify a single nutrient that can help intestinal cells to regenerate.

Yilmaz is the senior author of the study, which appears today in Nature. Koch Institute postdoc Fangtao Chi is the paper’s lead author.

Boosting regeneration

It is well-established that diet can affect overall health: High-fat diets can lead to obesity, diabetes, and other health problems, while low-calorie diets have been shown to extend lifespans in many species. In recent years, Yilmaz’s lab has investigated how different types of diets influence stem cell regeneration, and found that high-fat diets, as well as short periods of fasting, can enhance stem cell activity in different ways.

“We know that macro diets such as high-sugar diets, high-fat diets, and low-calorie diets have a clear impact on health. But at the granular level, we know much less about how individual nutrients impact stem cell fate decisions, as well as tissue function and overall tissue health,” Yilmaz says.

In their new study, the researchers began by feeding mice a diet high in one of 20 different amino acids, the building blocks of proteins. For each group, they measured how the diet affected intestinal stem cell regeneration. Among these amino acids, cysteine had the most dramatic effects on stem cells and progenitor cells (immature cells that differentiate into adult intestinal cells).

Further studies revealed that cysteine initiates a chain of events leading to the activation of a population of immune cells called CD8 T cells. When cells in the lining of the intestine absorb cysteine from digested food, they convert it into CoA, a cofactor that is released into the mucosal lining of the intestine. There, CD8 T cells absorb CoA, which stimulates them to begin proliferating and producing a cytokine called IL-22.

IL-22 is an important player in the regulation of intestinal stem cell regeneration, but until now, it wasn’t known that CD8 T cells can produce it to boost intestinal stem cells. Once activated, those IL-22-releasing T cells are primed to help combat any kind of injury that could occur within the intestinal lining.

“What’s really exciting here is that feeding mice a cysteine-rich diet leads to the expansion of an immune cell population that we typically don’t associate with IL-22 production and the regulation of intestinal stemness,” Yilmaz says. “What happens in a cysteine-rich diet is that the pool of cells that make IL-22 increases, particularly the CD8 T-cell fraction.”

These T cells tend to congregate within the lining of the intestine, so they are already in position when needed. The researchers found that the stimulation of CD8 T cells occurred primarily in the small intestine, not in any other part of the digestive tract, which they believe is because most of the protein that we consume is absorbed by the small intestine.

Healing the intestine

In this study, the researchers showed that regeneration stimulated by a cysteine-rich diet could help to repair radiation damage to the intestinal lining. Also, in work that has not been published yet, they showed that a high-cysteine diet had a regenerative effect following treatment with a chemotherapy drug called 5-fluorouracil. This drug, which is used to treat colon and pancreatic cancers, can also damage the intestinal lining.

Cysteine is found in many high-protein foods, including meat, dairy products, legumes, and nuts. The body can also synthesize its own cysteine, by converting the amino acid methionine to cysteine — a process that takes place in the liver. However, cysteine produced in the liver is distributed through the entire body and doesn’t lead to a buildup in the small intestine the way that consuming cysteine in the diet does.

“With our high-cysteine diet, the gut is the first place that sees a high amount of cysteine,” Chi says.

Cysteine has been previously shown to have antioxidant effects, which are also beneficial, but this study is the first to demonstrate its effect on intestinal stem cell regeneration. The researchers now hope to study whether it may also help other types of stem cells regenerate new tissues. In one ongoing study, they are investigating whether cysteine might stimulate hair follicle regeneration.

They also plan to further investigate some of the other amino acids that appear to influence stem cell regeneration.

“I think we’re going to uncover multiple new mechanisms for how these amino acids regulate cell fate decisions and gut health in the small intestine and colon,” Yilmaz says.

The research was funded, in part, by the National Institutes of Health, the V Foundation, the Koch Institute Frontier Research Program via the Kathy and Curt Marble Cancer Research Fund, the Bridge Project — a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center, the American Federation for Aging Research, the MIT Stem Cell Initiative, and the Koch Institute Support (core) Grant from the National Cancer Institute.

A more precise way to edit the genome

MIT researchers have dramatically lowered the error rate of prime editing, a technique that holds potential for treating many genetic disorders.

Anne Trafton | MIT News
September 17, 2025

A genome-editing technique known as prime editing holds potential for treating many diseases by transforming faulty genes into functional ones. However, the process carries a small chance of inserting errors that could be harmful.

MIT researchers have now found a way to dramatically lower the error rate of prime editing, using modified versions of the proteins involved in the process. This advance could make it easier to develop gene therapy treatments for a variety of diseases, the researchers say.

“This paper outlines a new approach to doing gene editing that doesn’t complicate the delivery system and doesn’t add additional steps, but results in a much more precise edit with fewer unwanted mutations,” says Phillip Sharp, an MIT Institute Professor Emeritus, a member of MIT’s Koch Institute for Integrative Cancer Research, and one of the senior authors of the new study.

With their new strategy, the MIT team was able to improve the error rate of prime editors from about one error in seven edits to one in 101 for the most-used editing mode, or from one error in 122 edits to one in 543 for a high-precision mode.

“For any drug, what you want is something that is effective, but with as few side effects as possible,” says Robert Langer, the David H. Koch Institute Professor at MIT, a member of the Koch Institute, and one of the senior authors of the new study. “For any disease where you might do genome editing, I would think this would ultimately be a safer, better way of doing it.”

Koch Institute research scientist Vikash Chauhan is the lead author of the paper, which appears today in Nature.

The potential for error

The earliest forms of gene therapy, first tested in the 1990s, involved delivering new genes carried by viruses. Subsequently, gene-editing techniques that use enzymes such as zinc finger nucleases to correct genes were developed. These nucleases are difficult to engineer, however, so adapting them to target different DNA sequences is a very laborious process.

Many years later, the CRISPR genome-editing system was discovered in bacteria, offering scientists a potentially much easier way to edit the genome. The CRISPR system consists of an enzyme called Cas9 that can cut double-stranded DNA at a particular spot, along with a guide RNA that tells Cas9 where to cut. Researchers have adapted this approach to cut out faulty gene sequences or to insert new ones, following an RNA template.

In 2019, researchers at the Broad Institute of MIT and Harvard reported the development of prime editing: a new system, based on CRISPR, that is more precise and has fewer off-target effects. A recent study reported that prime editors were successfully used to treat a patient with chronic granulomatous disease (CGD), a rare genetic disease that affects white blood cells.

“In principle, this technology could eventually be used to address many hundreds of genetic diseases by correcting small mutations directly in cells and tissues,” Chauhan says.

One of the advantages of prime editing is that it doesn’t require making a double-stranded cut in the target DNA. Instead, it uses a modified version of Cas9 that cuts just one of the complementary strands, opening up a flap where a new sequence can be inserted. A guide RNA delivered along with the prime editor serves as the template for the new sequence.

Once the new sequence has been copied, however, it must compete with the old DNA strand to be incorporated into the genome. If the old strand outcompetes the new one, the extra flap of new DNA hanging off may accidentally get incorporated somewhere else, giving rise to errors.

Many of these errors might be relatively harmless, but it’s possible that some could eventually lead to tumor development or other complications. With the most recent version of prime editors, this error rate ranges from one per seven edits to one per 121 edits for different editing modes.

“The technologies we have now are really a lot better than earlier gene therapy tools, but there’s always a chance for these unintended consequences,” Chauhan says.

Precise editing

To reduce those error rates, the MIT team decided to take advantage of a phenomenon they had observed in a 2023 study. In that paper, they found that while Cas9 usually cuts in the same DNA location every time, some mutated versions of the protein show a relaxation of those constraints. Instead of always cutting the same location, those Cas9 proteins would sometimes make their cut one or two bases further along the DNA sequence.

This relaxation, the researchers discovered, makes the old DNA strands less stable, so they get degraded, making it easier for the new strands to be incorporated without introducing any errors.

In the new study, the researchers were able to identify Cas9 mutations that dropped the error rate to 1/20th its original value. Then, by combining pairs of those mutations, they created a Cas9 editor that lowered the error rate even further, to 1/36th the original amount.

To make the editors even more accurate, the researchers incorporated their new Cas9 proteins into a prime editing system that has an RNA binding protein that stabilizes the ends of the RNA template more efficiently. This final editor, which the researchers call vPE, had an error rate just 1/60th of the original, ranging from one in 101 edits to one in 543 edits for different editing modes. These tests were performed in mouse and human cells.

The MIT team is now working on further improving the efficiency of prime editors, through further modifications of Cas9 and the RNA template. They are also working on ways to deliver the editors to specific tissues of the body, which is a longstanding challenge in gene therapy.

They also hope that other labs will begin using the new prime editing approach in their research studies. Prime editors are commonly used to explore many different questions, including how tissues develop, how populations of cancer cells evolve, and how cells respond to drug treatment.

“Genome editors are used extensively in research labs,” Chauhan says. “So the therapeutic aspect is exciting, but we are really excited to see how people start to integrate our editors into their research workflows.”

The research was funded by the Life Sciences Research Foundation, the National Institute of Biomedical Imaging and Bioengineering, the National Cancer Institute, and the Koch Institute Support (core) Grant from the National Cancer Institute.

Little picture, large revelations

A summer intensive using microscopy to study a unique type of yeast was a dream come true for BSG-MSRP-Bio student Adryanne Gonzalez.

Lillian Eden | Department of Biology
September 11, 2025

For Adryanne Gonzalez, studying yeast using microscopy at MIT this summer has been a dream come true. 

“Whatever world we’re living in, there’s an even smaller one,” Gonzalez says. “Knowing and understanding the smaller one can help us learn about the bigger stuff, and I think that’s so fascinating.” 

Gonzalez was part of the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology, working in the Lew Lab this summer. The program offers talented undergraduates from institutions with limited research opportunities at their home institutions the chance to spend 10 weeks at MIT, where they gain experience, hone skills, and create the types of connections with potential collaborators and future colleagues that are critical for success in academia. 

Gonzalez was so excited about the opportunity that she didn’t apply for any other summer programs.  

“I really wanted to work on becoming more independent in the lab, and this program was research-intensive, and you get to lead your own project,” she says. “It was this or nothing.”

two people standing at a bench in front of a computer
Adryanne Gonzalez, right, with her mentor, Lew Lab graduate student Clara Fikry, left. Gonzalez spent the summer studying Aureobasidium pullulans, a type of yeast that produces large, root-like networks. Photo credit: Mandana Sassanfar/MIT Department of Biology

The fun of science & the rigors of mentoring

The Lew Lab works with two different specimens: a model baker’s yeast that multiplies by producing a round growth called a bud that eventually separates into a separate, daughter cell; and Aureobasidium pullulans, which is unusual because it can create multiple buds at the same time, and can also spread in large networks of branching, rootlike growths called hyphae. A. pullulans is an emerging model system, meaning that researchers are still defining what normal growth and behavior is for the fungus, like how it senses and responds to obstacles, and how resources and molecular machinery are allocated to its branching structures.  

“I’m really interested in all the diversity of biology that we don’t get to study if we’re only focused on the model species,” says Clara Fikry, a graduate student in the Lew Lab and Gonzalez’s mentor for the summer. 

On the mentoring side, Fikry learned how to balance providing a rigorous workload while not overwhelming her mentee with information. 

“Science should be fun,” Fikry says. “The goal of this isn’t to produce as much data as possible; it’s to learn what the process of science is like.”

Although her day-to-day work was with Fikry, Gonzalez also received guidance from Daniel Lew himself. For example, his advice was invaluable for honing a draft of her research statement for potential graduate school applications, which she’d previously written as part of a class assignment.

“It was an assignment where I needed to hit a page count, and he pointed out that I kind of wrote the same thing three times in the first paragraph,” she shares with a laugh. He helped her understand that “when you’re writing something professionally, you want your writing to be concise and understandable to a broad spectrum of readers.” 

Life in the cohort

The BSG-MSRP-Bio program gives undergraduate students a taste of what the day-to-day life of graduate school might feel like, from balancing one’s workload and reading research papers to learning new techniques and troubleshooting when experiments don’t go as planned. Gonzalez recalls that the application process felt very “adult” and “professional” because she was responsible for reaching out to the faculty member of the lab she was interested in on her own behalf, rather than going through a program intermediary. 

Gonzalez is one of just three students from Massachusetts participating in the program this year—the program draws students from across the globe to study at MIT. 

Every student also arrives with different levels of experience, from Gonzalez, who can only work in a lab during the school year about once a week, to Calo Lab student Adriana Camacho-Badillo, who is in her third consecutive summer in the program, and continuing work on a project she began last year.

“We’re all different levels of novice, and we’re coming together, and we’re all really excited about research,” Gonzalez says.

Gonzalez is a Gould Fellow, supported at MIT through the generous donations of Mike Gould and Sara Moss. The program funding was initiated in 2015 to honor the memory of Gould’s parents, Bernard S. and Sophie G. Gould. Gould and Moss take the time to come to campus and meet the students they’re supporting every year. 

“You don’t often get to meet the person that’s helping you,” Gonzalez said. “They were so warm and welcoming, and at the end, when they were giving everyone a nice, firm handshake, Mike Gould said, ‘Make sure you keep going. Don’t give up,’ which was so sweet.” 

Gonzalez is also supported by Cedar Tree, a Boston-based family foundation that primarily funds local environmental initiatives. In the interest of building a pipeline for future scientists with potential interest in the environmental sciences and beyond, Cedar Tree recently established a grant program for local high school and undergraduate students pursuing STEM research and training opportunities. 

Gonzalez discusses her summer research with attendees of the poster session that serves as the culmination of the 10-week summer research intensive for talented non-MIT undergraduate students from around the world. Photo credit: Lillian Eden/MIT Department of Biology.

Preparing for the future

The BSG-MSRP-Bio program culminates with a lively poster session where students present their summer projects to the MIT community—the first time some students are presenting their data to the public in that format.

Although the program is aimed at students who foresee a career in academia, the majority of students who participate are uncertain about the specific field, organism, or process they’ll eventually want to study during a PhD program. For Gonzalez, the program has helped her feel more prepared for the potential rigors of academic research.

“I think the hardest thing about this program is convincing yourself to apply,” she says. “Don’t let that hinder you from exploring opportunities that may seem out of reach.” 

Inflammation jolts “sleeping” cancer cells awake, enabling them to multiply again

A paper from the Weinberg Lab indicates that inflammation may be a factor in how metastatic cancer cells, those that have broken away from the original tumor, can erupt into a frenzy of growth and division months, years, or decades after initial treatment, seeding new, life-threatening tumors.

Shafaq Zia | Whitehead Institute
September 3, 2025

This migration of cancer cells, called metastasis, is especially common in breast cancer. For many patients, the disease can return months—or even decades—after initial treatment, this time in an entirely different organ.

Whitehead Institute Founding Member Robert Weinberg, also the Daniel K. Ludwig Professor for Cancer Research at Massachusetts Institute of Technology (MIT), has spent decades unraveling the complex biology of metastasis and pursuing research that could improve survival rates among patients with metastatic breast cancer—or prevent metastasis altogether.

In their latest study, Weinberg, postdoctoral fellow Jingwei Zhang, and colleagues ask a critical question: what causes these dormant cancer cells to erupt into a frenzy of growth and division? The group’s findings, published Sept. 1 in The Proceedings of the National Academy of Sciences (PNAS), point to a unique culprit.

This awakening of dormant cancer cells, they’ve discovered, isn’t a spontaneous process. Instead, the wake-up call comes from the inflamed tissue surrounding the cells. One trigger for this inflammation is bleomycin, a common chemotherapy drug that can scar and thicken lung tissue.

“The inflammation jolts the dormant cancer cells awake,” Weinberg says. “Once awakened, they start multiplying again, seeding new life-threatening tumors in the body.”

Decoding metastasis

There’s a lot that scientists still don’t know about metastasis, but this much is clear: cancer cells must undergo a long and arduous journey to achieve it. The first step is to break away from their neighbors within the original tumor.

Normally, cells stick to one another using surface proteins that act as molecular “velcro” but some cancer cells can acquire genetic changes that disrupt the production of these proteins and make them more mobile and invasive, allowing them to detach from the parent tumor.

Once detached, they can penetrate blood vessels and lymphatic channels, which act as highways to distant organs.

While most cancer cells die at some point during this journey, a few persist. These cells exit the bloodstream and invade different tissues—lungs, liver, bone, and even the brain—to give birth to new, often more aggressive tumors.

“Almost 90% of cancer-related deaths occur not from the original tumor but when cancer cells spread to other parts of the body,” says Weinberg. “This is why it’s so important to understand how these ‘sleeping’ cancer cells can wake up and start growing again.”

Setting up shop in new tissue comes with changes in surroundings—the “tumor microenvironment”—to which the cancer cells may not be well-suited. These cells face constant threats, including detection and attack by the immune system.

To survive, they often enter a protective state of dormancy that puts a pause on growth and division. This dormant state also makes them resistant to conventional cancer treatments, which often target rapidly dividing cells.

To investigate what makes this dormancy reversible months or years down the line, researchers in the Weinberg Lab injected human breast cancer cells into mice. These cancer cells were modified to produce a fluorescent protein, allowing the scientists to track their behavior in the body.

The group then focused on cancer cells that had lodged themselves in the lung tissue. By examining them for specific proteins—Ki67, ITGB4 and p63—that act as markers of cell activity and state, the researchers were able to confirm that these cells were in a non-dividing, dormant state.

Previous work from the Weinberg Lab had shown that inflammation in organ tissue can provoke dormant breast cancer cells to start growing again. In this study, the team tested bleomycin—a chemotherapy drug known to cause lung inflammation—that can be given to patients after surgery to lower the risk of cancer recurrence.

The researchers found that lung inflammation from bleomycin was sufficient to trigger the growth of large lung cancer colonies in treated mice—and to shift the character of these once dormant cells to those that are more invasive and mobile.

Zeroing in on the tumor microenvironment, the team identified a type of immune cells, called M2 macrophages, as drivers of this process. These macrophages release molecules called epidermal growth factor receptor (EGFR) ligands, which bind to receptors on the surface of dormant cancer cells. This activates a cascade of signals that provoke dormant cancer cells to start multiplying rapidly.

But EGFR signaling is only the initial spark that ignites the fire. “We found that once dormant cancer cells are awakened, they retain what we call an ‘awakening memory,’” Zhang says. “They no longer require ongoing inflammatory signals from the microenvironment to stay active [growing and multiplying]—they remember the awakened state.”

While signals related to inflammation are necessary to awaken dormant cancer cells, exactly how much signaling is needed remains unclear. “This aspect of cancer biology is particularly challenging because multiple signals contribute to the state change in these dormant cells,” Zhang says.

The team has already identified one key player in the awakening process but understanding the full set of signals and how each contributes is far more complex—a question they are continuing to investigate in their new work.

Studying these pivotal changes in the lives of cancer cells—such as their transition from dormancy to active growth—will deepen our scientific understanding of metastasis and, as researchers in the Weinberg Lab hope, lead to more effective treatments for patients with metastatic cancers.

Rudolf Jaenisch awarded Ogawa-Yamanaka Stem Cell Prize

Rudolf Jaenisch is recognized for his trailblazing contributions to epigenetics and stem cell biology, which have shaped modern regenerative medicine.

Sarah Stanley | Gladstone Institutes
August 28, 2025

Rudolf Jaenisch, MD, was announced today as the recipient of the 2025 Ogawa-Yamanaka Stem Cell Prize by Gladstone Institutes. He was selected for his trailblazing contributions to epigenetics and stem cell biology. His pivotal discoveries have profoundly advanced our understanding of gene regulation, cellular reprogramming, and the potential of regenerative medicine.

A founding member of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, Jaenisch is also a professor of biology at the Massachusetts Institute of Technology. He is widely recognized for his role in establishing the use in science of induced pluripotent stem (iPS) cells—adult cells that have been reprogrammed into an embryonic stem cell–like state with the potential to become any cell type in the body.

Among his many achievements, Jaenisch was the first to show the potential therapeutic applications of iPS cells after they were discovered by Gladstone Senior Investigator Shinya Yamanaka, MD, PhD. In fact, Jaenisch effectively cured mice of sickle cell anemia by using iPS cells that had been derived from the animals’ own skin cells and in which the disease-causing genetic defect had been corrected.

“Until then, iPS cells were just an exciting lab tool—but Dr. Jaenisch provided the first real proof that they could be used to treat human disease,” says Deepak Srivastava, MD, chair of the selection committee, president of Gladstone Institutes, and director of the Rodenberry Stem Cell Center at Gladstone. “We’re very happy to recognize his outstanding career with this year’s award. His many contributions to stem cell research and disease modeling have helped shape modern regenerative medicine as we know it.”

Jaenisch has been at the forefront of exploring, expanding, and refining the processes by which iPS cells are created and applied in labs around the world. His work has opened the door to the development of therapies for a wide range of genetic and degenerative diseases.

Since its establishment in 2015, the Ogawa-Yamanaka Stem Cell Prize has honored scientists and doctors leading groundbreaking work in translational regenerative medicine using reprogrammed cells. Each year, it is made possible by a generous gift from the Hiro and Betty Ogawa family.

The prize, supported by Gladstone and Cell Press, also pays tribute to Yamanaka, whose discovery of iPS cells earned him a Nobel Prize in 2012 and is tightly intertwined with Jaenisch’s work.

“Shinya’s discovery completely transformed the world of stem cell science and opened up so many promising new paths for understanding and addressing disease,” Jaenisch says. “What an honor it is to be recognized for my contributions in this field.”

One of Jaenisch’s earliest marks on science came in 1974, when he co-created the first transgenic animal—an organism whose genetic material has been intentionally altered by adding foreign genes—with pioneering embryologist Beatrice Mintz, PhD. This work became the foundation for genetically engineered animal models, which are used in nearly every area of biomedical research today.

“This single study was a major leap in molecular biology,” says Srivastava. “It gave birth to the very concept of modeling human diseases in animals, allowing scientists to deliberately change an animal’s genetic code in order to study the mechanisms of disease and test therapies.”

In his more than 40 years at the Whitehead Institute, Jaenisch has led research exploring how stem cells and reprogramming technologies could be harnessed to better understand and treat disease. In the process, he has continued to develop innovative tools, including adapting CRISPR technology for gene editing and epigenome editing in stem cell systems.

An independent committee of international stem cell experts selected Jaenisch for the 2025 Ogawa-Yamanaka Stem Cell Prize from a highly competitive pool of nominees. As this year’s winner, he will receive an unrestricted prize of $150,000. Gladstone will host a ceremony on December 1, 2025, in San Francisco, California, where Jaenisch will deliver a scientific lecture and be presented with the award.

About Gladstone Institutes

Gladstone Institutes is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. Established in 1979, it is located in the epicenter of biomedical and technological innovation, in the Mission Bay neighborhood of San Francisco. Gladstone has created a research model that disrupts how science is done, funds big ideas, and attracts the brightest minds.

About Rudolf Jaenisch

Rudolf Jaenisch, MD, is a founding member of the Whitehead Institute for Biomedical Research and a professor of biology at the Massachusetts Institute of Technology. He is a pioneer of transgenic science, in which an animal’s genetic makeup is altered.

Jaenisch received his MD from the University of Munich in 1967 and carried out postdoctoral research at Princeton University, Fox Chase Institute for Cancer Research, and the Salk Institute. Before joining Whitehead in 1982, he was head of the Department of Tumor Virology at the Heinrich Pette Institute at the University of Hamburg.

His current research focuses on the epigenetic regulation of gene expression, which has led to major advances in creating embryonic stem cells and iPS cells, as well as their therapeutic applications. His lab also focuses on the epigenetic mechanisms involved in cancer and brain development, as well as coronavirus biology.

Jaenisch has co-authored more than 500 research papers and received various awards during his career, including the Max Delbrück Medal, the Vilcek Prize, the National Medal of Science, the Wolf Prize in Medicine, and the Otto Warburg Medal. He is a fellow of the American Academy of Arts and Sciences and an elected member of the U.S. National Academy of Sciences. He also was president of the International Society for Stem Cell Research in 2014–15.

About the Ogawa-Yamanaka Stem Cell Prize

The Ogawa-Yamanaka Stem Cell Prize recognizes individuals whose original translational research has advanced cellular reprogramming technology for regenerative medicine. Supported by Gladstone Institutes, in partnership with Cell Press, the prize was established in 2015 through a generous gift from Betty and Hiro Ogawa. It has been maintained through their sons, Andrew and Marcus Ogawa, to honor the Ogawas’ memory by continuing the philanthropic legacy they shared during their 46-year marriage. It also recognizes the importance of induced pluripotent stem cells (iPS cells), discovered by Gladstone Senior Investigator and Nobel laureate Shinya Yamanaka, MD, PhD.

Past recipients include Masayo Takahashi, MD, PhD, in 2015; Douglas Melton, PhD, in 2016; Lorenz Studer, MD, in 2017; Marius Wernig, MD, PhD, in 2018; Gordon Keller, PhD, in 2019; Juan Carlos Izpisua Belmonte, PhD, in 2022; Magdalena Zernicka-Goetz, PhD, in 2023; and Rusty Gage, PhD, in 2025.

The 2025 selection committee was composed of George Daley, MD, PhD, dean of Harvard Medical School; Hideyuki Okano, MD, PhD, dean of the School of Medicine at Keio University; Deepak Srivastava, MD, president of Gladstone Institutes and director of the Roddenberry Stem Cell Center at Gladstone; Lorenz Studer, MD, director of the Center for Stem Cell Biology at Memorial Sloan Kettering Cancer Center; Fiona Watt, FRS, FMedSci, director of the Centre for Stem Cells and Regenerative Medicine at King’s College, London; and Shinya Yamanaka, MD, PhD, senior investigator at Gladstone and director emeritus of the Center for iPS Cell Research and Application at Kyoto University.

3 Questions: Mariely Morales Burgos on the BSG-MSRP-Bio program

Undergraduate student and Gould Fellow discusses choosing a summer research lab, living in the Greater Boston Area, and managing imposter syndrome.

Lillian Eden | Department of Biology
August 28, 2025

Mariely Morales Burgos first fell in love with MIT while participating in the Quantitative Methods Workshop, a weeklong intensive offered in January to prepare students to analyze data in biology and neuroscience. Those skills have come in handy this summer while participating in the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology (BSG-MSRP-Bio), a ten-week training program for non-MIT undergraduate students interested in pursuing an academic career.

A Gould Fellow and McNair Scholar, Morales Burgos spent the summer mentored by Associate Professor of Biology Eliezer Calo, for whom the program served as a critical stepping stone in his own career. Calo is the first BSG-MSRP-Bio program alum to receive tenure at MIT. 

A rising senior at the University of Puerto Rico at Aguadilla, Morales Burgos spent the summer using zebrafish to study the molecular machinery responsible for making proteins. 

Three people standing in an interior lab space smiling at the camera
(from right to left) Mariely Morales Burgos, mentor and Associate Professor of Biology Eliezer Calo, and Adriana Camacho-Badillo in the lab at MIT. Camacho-Badillo, a returning BSG-MSRP-Bio student, encouraged Morales Burgos to apply for the program. Photo Credit: Mandana Sassanfar/MIT Department of Biology.

Q: How did you select your lab, and what have you been working on?

A: I knew I wanted to work in Eliezer’s lab after meeting him during a QMW faculty lunch. I felt like we really connected because of his genuine passion for science, commitment to his trainees, and the way he spoke about his lab and the care he puts into mentoring. 

My research focuses on ribosomes, which are the protein factories of the cell, and they’re essential to make what the cell needs to go through different developmental stages and through its most crucial processes. In early development, zebrafish and numerous other organisms depend on maternally deposited ribosomes and associated molecular components inherited directly from the oocyte. As time goes on, their own genomes activate, and they start being able to make their own ribosomes. What I’m studying is this transition from maternal to zygotic ribosomes during early development. We know this transition happens, but we don’t know how this transition is regulated, whether it happens passively, through dilution, or actively, through targeted cellular mechanisms.  

One skill that I’ve been able to learn here, other than just learning and applying techniques, is how to develop a whole project independently, how to think critically about the next step of my project, and what other questions I can ask.

Being able to work with a live animal organism and see the developmental stages in real-time, I thought that was really cool. And it really makes me appreciate the beauty of developmental biology, and just life in general.

Q: How did you prepare for the program, and what has it been like living and working in Boston and Cambridge? As a Gould Fellow, you also met with program supporters Mike Gould and Sara Moss, who established the Bernard S. and Sophie G. Gould fund to honor the memory of Mike’s parents. What was it like to meet and talk to Mike and Sara? 

A: Once we get accepted, we’re encouraged to start communication with our faculty. I had a few meetings with Eliezer to discuss some papers, and based on our discussion and the expectations for the project, I was able to read more and start preparing before I arrived.

Every few weeks beforehand, we had a meeting with Mandana and the rest of the cohort on Zoom, and we were talking on an app called GroupMe, and we exchanged socials, so when we came here, we weren’t complete, total strangers. 

When I’m not in the lab, I spend a lot of time with my roommates, and we like walking around Boston. It’s a very walkable city and has a lot of unique architecture, but Boston weather is very unpredictable. I’m from a tropical island, so I wish someone had told me to prepare for the rain and cold, but the July weather has been so nice. 

In Puerto Rico, you don’t have public transportation, so I’ve really enjoyed commuting. Our dorms are at Northeastern, so I take the bus, and it goes over the Charles, and it’s so beautiful. 

I’m a person who feels a lot of emotions, so I was the only one who cried when we met the Goulds. It was a bit embarrassing, but that’s okay. They told me to never lose the empathy that I have, no matter how hard my journey is, to keep on holding on to my sentimental side and keep working hard, and they’re so excited to see where we end up and what we end up doing.

Mariely Morales Burgos standing in front of a paper poster, indicating a certain point of data to three people
The summer research intensive culminated in a lively poster session. Photo Credit: Lillian Eden/MIT Department of Biology

Q: This program’s aim is to make research available for students who don’t have access to hands-on experience at their home institutions, so many students, including you, are embarking on independent research projects for the first time, which could trigger “imposter syndrome.” What was that experience like for you, and what advice would you give to future BSG-MSRP-Bio program participants? 

A: I was a little bit intimidated by the program, and didn’t apply the first time I had the opportunity. Then I did the Quantitative Methods Workshop, and those eight days were beautiful. I got to see how everybody loves collaborating and that the community here is very supportive. I met many wonderful faculty who were passionate about their research, and that exposure made me realize I would love to be part of a place like this. 

Imposter syndrome is something that I feel like most everybody deals with, but MSRP is a place that, if you’re willing to put in the work, everyone is willing to help you reach the places that you dream of being. It might feel intimidating to ask questions, and you could be scared of feeling like you don’t deserve to be in these spaces. But somebody who wants you to grow will answer your questions. I wanted to be able to work independently as soon as possible, because that really showcases your abilities, but no matter what, Eliezer, who’s mentoring me, his door is always open. 

What I advise is to really dive into your project and take advantage of everything this program offers. Working hard on your project, you get to fall in love with the process and the questions you’re trying to answer and science as a whole, and there’s nothing better than to spend the summer on a project that you love.

Locally produced proteins help mitochondria function

One of the ways that cells ensure proteins end up where they're needed is creating them at that location, through a process called localized translation. New research from the Weissman Lab has expanded our understanding localized translation at mitochondria and sheds light on the organizational principles of genes and the proteins they encode.

Greta Friar | Whitehead Institute
August 27, 2025

Now, Weissman, who is also a professor of biology at the Massachusetts Institute of Technology and an HHMI Investigator, and postdoc in his lab Jingchuan Luo have expanded our knowledge of localized translation at mitochondria, structures that generate energy for the cell. In a paper published in Cell on August 27, they share a new tool, LOCL-TL, for studying localized translation in close detail, and describe the discoveries it enabled about two classes of proteins that are locally translated at mitochondria.

The importance of localized translation at mitochondria relates to their unusual origin. Mitochondria were once bacteria that lived within our ancestors’ cells. Over time the bacteria lost their autonomy and became part of the larger cells, which included migrating most of their genes into the larger cell’s genome in the nucleus. Cells evolved processes to ensure that proteins needed by mitochondria that are encoded in genes in the larger cell’s genome get transported to the mitochondria. Mitochondria retain a few genes in their own genome, so production of proteins from the mitochondrial genome and that of the larger cell’s genome must be coordinated to avoid mismatched production of mitochondrial parts. Localized translation may help cells to manage the interplay between mitochondrial and nuclear protein production—among other purposes.

How to detect local protein production

For a protein to be made, genetic code stored in DNA is read into RNA, and then the RNA is read or translated by a ribosome, a cellular machine that builds a protein according to the RNA code. Weissman’s lab previously developed a method to study localized translation by tagging ribosomes near a structure of interest, and then capturing the tagged ribosomes in action and observing the proteins they are making. This approach, called proximity-specific ribosome profiling, allows researchers to see what proteins are being made where in the cell. The challenge that Luo faced was how to tweak this method to capture only ribosomes at work near mitochondria.

Ribosomes work quickly, so a ribosome that gets tagged while making a protein at the mitochondria can move on to making other proteins elsewhere in the cell in a matter of minutes. The only way researchers can guarantee that the ribosomes they capture are still working on proteins made near the mitochondria is if the experiment happens very quickly.

Weissman and colleagues had previously solved this time sensitivity problem in yeast cells with a ribosome-tagging tool called BirA that is activated by the presence of the molecule biotin. BirA is fused to the cellular structure of interest, and tags ribosomes it can touch—but only once activated. Researchers keep the cell depleted of biotin until they are ready to capture the ribosomes, to limit the time when tagging occurs. However, this approach does not work with mitochondria in mammalian cells because they need biotin to function normally, so it cannot be depleted.

Luo and Weissman adapted the existing tool to respond to blue light instead of biotin. The new tool, LOV-BirA, is fused to the mitochondria’s outer membrane. Cells are kept in the dark until the researchers are ready. Then they expose the cells to blue light, activating LOV-BirA to tag ribosomes. They give it a few minutes and then quickly extract the ribosomes. This approach proved very accurate at capturing only ribosomes working at mitochondria.

The researchers then used a method originally developed by the Weissman lab to extract the sections of RNA inside of the ribosomes. This allows them to see exactly how far along in the process of making a protein the ribosome is when captured, which can reveal whether the entire protein is made at the mitochondria, or whether it is partly produced elsewhere and only gets completed at the mitochondria.

“One advantage of our tool is the granularity it provides,” Luo says. “Being able to see what section of the protein is locally translated helps us understand more about how localized translation is regulated, which can then allow us to understand its dysregulation in disease and to control localized translation in future studies.”

Two protein groups are made at mitochondria

Using these approaches, the researchers found that about twenty percent of the genes needed in mitochondria that are located in the main cellular genome are locally translated at mitochondria. These proteins can be divided into two distinct groups with different evolutionary histories and mechanisms for localized translation.

One group consists of relatively long proteins, each containing more than 400 amino acids or protein building blocks. These proteins tend to be of bacterial origin—present in the ancestor of mitochondria—and they are locally translated in both mammalian and yeast cells, suggesting that their localized translation has been maintained through a long evolutionary history.

Like many mitochondrial proteins encoded in the nucleus, these proteins contain a mitochondrial targeting sequence (MTS), a zip code that tells the cell where to bring them. The researchers discovered that most proteins containing an MTS also contain a nearby inhibitory sequence that prevents transportation until they are done being made. This group of locally translated proteins lacks the inhibitory sequence, so they are brought to the mitochondria during their production.

Production of these longer proteins begins anywhere in the cell, and then after approximately the first 250 amino acids are made, they get transported to the mitochondria. While the rest of the protein gets made, it is simultaneously fed into a channel that brings it inside the mitochondria. This ties up the channel for a long time, limiting import of other proteins, so cells can only afford to do this simultaneous production and import for select proteins. The researchers hypothesize that these bacterial-origin proteins are given priority as an ancient mechanism to ensure that they are accurately produced and placed within mitochondria.

The second locally translated group consists of short proteins, each less than 200 amino acids long. These proteins are more recently evolved, and correspondingly, the researchers found that the mechanism for their localized translation is not shared by yeast. Their mitochondrial recruitment happens at the RNA level. Two sequences within regulatory sections of each RNA molecule that do not encode the final protein instead code for the cell’s machinery to recruit the RNAs to the mitochondria.

The researchers searched for molecules that might be involved in this recruitment, and identified the RNA binding protein AKAP1, which exists at mitochondria. When they eliminated AKAP1, the short proteins were translated indiscriminately around the cell. This provided an opportunity to learn more about the effects of localized translation, by seeing what happens in its absence. When the short proteins were not locally translated, this led to the loss of various mitochondrial proteins, including those involved in oxidative phosphorylation, our cells’ main energy generation pathway.

In future research, Weissman and Luo will delve deeper into how localized translation affects mitochondrial function and dysfunction in disease. The researchers also intend to use LOCL-TL to study localized translation in other cellular processes, including in relation to embryonic development, neural plasticity, and disease.

“This approach should be broadly applicable to different cellular structures and cell types, providing many opportunities to understand how localized translation contributes to biological processes,” Weissman says. “We’re particularly interested in what we can learn about the roles it may play in diseases including neurodegeneration, cardiovascular diseases, and cancers.”

Luo et al. “Proximity-specific ribosome profiling reveals the logic of localized mitochondrial translation.” Cell, August 27, 2025. https://doi.org/10.1016/j.cell.2025.08.002

Can bacteria be used to clean up oil spills?

The Drennan Lab is working on insights into how nature performs challenging chemistry in oxygen-free environments, with potential applications for remediation, such as cleaning up oil spills, in situations where traditional approaches are ineffective.

Produced by Lillian Eden | Department of Biology
August 28, 2025

Can bacteria clean up oil spills? The short answer: no. Or, at least, not yet.

The Drennan Lab is working to understand how bacteria perform incredible, radical chemistry on inert compounds. Inert compounds, like those that make up crude oil, are challenging to break down because they contain very stable chains of carbon and hydrogen (hydrocarbons). Some microbes have special enzymes that attach another compound to these long, hydrocarbon chains, which makes it possible for the previously inert compound to be degraded. 

Using cryo-electron microscopy, the Drennan Lab recently determined the three-dimensional structure of a glycyl radical enzyme that catalyzes the formation of carbon-carbon bonds, outlined in a recent paper published in PNAS.

This work provides insights into how nature performs challenging chemistry in oxygen-free environments and has potential applications for remediation, such as cleaning up oil spills, in situations where traditional approaches are ineffective. 

This research was led by former postdoc Mary C. Andorfer, who will continue to explore the power of anaerobic microbes as an Assistant Professor at Michigan State University. This work was funded by the National Institutes of Health. Catherine Drennan is a Professor of Biology and Chemistry at MIT and a Howard Hughes Medical Institute Investigator.