On June 9, the McGovern Institute convened leaders in science, biotechnology, and patient advocacy for RareNet 2026, a first-of-its-kind symposium aimed at dismantling the barriers between laboratory discovery and life-changing treatments for rare brain disorders.
Over 300 million people worldwide live with rare disorders—most affecting the brain and nervous system. Yet the vast majority lack an approved therapy. The Rare Brain Disorders Nexus (RareNet) was established at the McGovern Institute in 2025 by MIT alums Ana Méndez ’91 and Rajeev Jayavant ’86, (EE ’88, SM ’88) to address this need. Led by Guoping Feng, the James W. (1963) and Patricia T. Poitras Professor of Neuroscience at MIT, RareNet draws together expertise from the MIT community and beyond to expedite the path from lab to clinic.
MIT President Sally Kornbluth set the tone at the inaugural RareNet symposium, thanking founders Méndez and Jayavant for helping MIT focus on this important challenge: “I look forward to watching RareNet dissolve needless barriers, accelerate timelines, and bring new hope to millions of patients and their families for whom hope is long overdue.”
MIT President Sally Kornbluth (third from left) with RareNet founders Rajeev Jayavant (far left) and Ana Méndez (center) at the June 9 symposium at the McGovern Institute. Also pictured are the founders’ son Neal (second from left), RareNet Director Guoping Feng, RareNet Scientific Advisor Xian Gao, and McGovern Institute Director Robert Desimone. Photo: Steph Stevens
RareNet’s collaborative vision came into focus at the symposium, where more than a dozen leading neuroscientists, biotech innovators, and patient advocates shared the podium. The scientific program spanned the full translational pathway, from fundamental discovery to clinical development.
Feng Zhang (McGovern Institute, MIT; HHMI; Broad Institute), Katherine High (RhyGaze AG; Rockefeller University), Kiran Musunuru (University of Pennsylvania), and Timothy Yu (Boston Children’s Hospital; Harvard Medical School) discussed emerging genetic medicines–including genome editing, gene therapy, and individualized therapeutic strategies–and the challenges involved in bringing them safely to patients.
Kevin Bender (University of California San Francisco), Christopher Walsh (Boston Children’s Hospital; Harvard Medical School), Sonia Vallabh (Broad Institute; MGH; Harvard Medical School), and Joseph Buxbaum (Icahn School of Medicine at Mount Sinai) explored how insights into disease mechanisms, human genetics, and patient-derived data are advancing research in neurodevelopmental disorders, autism, and prion disease.
Representatives from the Sturge-Weber and FOXP1 communities–including Karen Ball, Matt Shirley, and Samit Dasgupta–demonstrated how patient foundations can help define research priorities, build essential resources, and drive promising discoveries toward meaningful treatments.
Also among the day’s speakers was Monica Coenraads, who transformed her child’s rare disease into a powerful research initiative. When her daughter Chelsea was diagnosed with Rett syndrome in 1998 at age two, Coenraads faced an uncertain future. Today, as founder and CEO of the Rett Syndrome Research Trust, she is helping to rewrite that story for other families. In a compelling talk with John Sinnamon, Director of Research at RSRT, Coenraads shared both the scientific breakthroughs reshaping Rett syndrome treatment and the deeply personal journey that sparked it all.
“Monica and John’s talks capture the vital connection between patients and families, cutting-edge research, and translational innovation,” says RareNet Executive Director Xian Gao. “It’s a powerful reminder that behind every research breakthrough is a human story demanding progress.”
by Stefanie Koperniak | Office of Graduate Education |
Shannon Knight attributes her interest in neuroscience to an experience she had in high school. She and her sister attended a medical day for students at the nearby University of Illinois Chicago. As they were on their way out of the event, they walked past a room with a person holding a brain.
“We stopped and backpedaled into the room, and I was so fascinated,” says Knight. “I was able to hold the brain of a patient who had passed away of Alzheimer’s. The brain holds so much emotion, decision-making — everything. I realized that this man’s entire memory was in my hands, and something clicked for me. I decided that I really wanted to learn much more about this organ.”
Now in her sixth year of doctoral studies at MIT’s McGovern Institute for Brain Research, Knight is working on developing a novel gene therapy for childhood-onset epilepsy, specifically SYNGAP1 haploinsufficiency. This rare genetic disorder is caused by a mutation in the SYNGAP1 gene, rendering one of the two copies of the gene nonfunctional.
SYNGAP1 is important for brain development and neuronal communication, and the disorder leads to seizures in children starting as young as 4 months old. Other symptoms include intellectual disabilities, challenges with eating and sleeping, and difficulties with movement.
While there are currently methods to address the symptoms of the disorder, such as anti-seizure medications and dietary restrictions, as the child ages, the seizures often become resistant to medications. Knight is working to develop a therapeutic using CRISPR, a biotechnology tool used to edit genes. This therapeutic aims to address the root cause of this medication resistance by focusing on the gene itself.
“The idea of leading science with empathy is something that I feel very deeply,” she says. “I hope my efforts in the lab work toward the benefit of the people affected, rather than just for the benefit of my own science.”
Researching gene therapies
Knight’s interest in the brain flourished as a neuroscience major at Bowdoin College, working with Professor Hadley Horch. While she had originally planned to be pre-med, Knight ultimately decided that it wasn’t the best fit. She enjoyed the research she did as part of her honors thesis, exploring the regeneration of neurons in the auditory system of crickets, and decided that she wanted to pursue more research in molecular neuroscience, as well as genetics.
After graduating, Knight worked at the Perrimon Lab at Harvard University, where she first learned about CRISPR, applying it in a fruit fly model. She worked for two years in the lab, co-authoring a few papers and applying to graduate schools.
She ultimately landed in the lab of MIT Professor Guoping Feng, studying the potential of utilizing CRISPR to develop a gene therapy treatment for Phelan-McDermid Syndrome, a rare genetic disorder caused by a deletion or mutation on the 22nd chromosome.
“Many of our graduate students are passionate about making a positive impact to society through cutting-edge research, and Shannon is a perfect example,” says Feng, the James W. and Patricia T. Poitras Professor and associate director at the McGovern Institute. “She is developing gene therapy technologies that have the potential to help many kids with devastating neurodevelopmental disorders.”
Building off of the gene therapy research around Phelan-McDermid syndrome, which is now in clinical trials in patients, Knight is now in the early phases of testing gene therapy for SYNGAP1 disorder. The goal is to go through the same process for the SYNGAP1 gene therapy as for the Phelan-McDermid gene therapy — eventually obtaining U.S. Food and Drug Administration approval and beginning clinical trials.
The testing of the gene therapy on mice with a version of SYNGAP1 disorder has alleviated seizures and all of the behavioral phenotypes. This promising work is being accelerated by the Rare Brain Disorders Nexus, an MIT initiative that launched in the fall of 2025.
“Something I think about a lot is the idea of who ‘deserves’ the attention of a gene therapy. I feel that, regardless of how rare a genetic disorder might be, it still deserves care,” says Knight. “SYNGAP1 disorder is extremely rare, only impacting one to four out of every 10,000 children. I am very fortunate to be at an institution like MIT that has so many labs and brilliant researchers working on diseases that impact large portions of society, and it was really important to me to spend my PhD years helping a small, often unseen population. Although I don’t actually have a relationship with someone who has SYNGAP1 disorder, I know so many people who feel invisible in systems, and it is really important to me to be able to focus on people who feel unseen and give them hope.”
Inspiring others in the lab
In addition to her passion for neuroscience and genetic research, Knight has also developed a love of teaching. She has been a teaching assistant for class 9.12 (Experimental Molecular Neurobiology), leading the lab portion of the course. She has enjoyed working closely with small classes of students, introducing them to the fundamentals of neuroscience lab research.
“We walked through the process of looking at a specific protein in neurons, and talked about how you can go from cell culture all the way up to a mouse brain — and all the steps in between,” she says. “It was so important to me to be able to teach the students and help them to consider all of the different types of experiments they could do.”
Knight received the Goodwin Medal in 2025 in recognition of her commitment to excellent teaching.
“I’ve talked to many of the students since then,” she says, “and many said it was one of their favorite classes.”
Schizophrenia, a complex and variable psychiatric disorder, changes people’s perceptions of reality. People with schizophrenia may hear, see, or sense things that aren’t there, and they often hold firm to mistaken ideas about the world despite strong evidence to the contrary. As if these changes aren’t disruptive enough, they are usually accompanied by cognitive difficulties and disorganized thinking.
Scientists at the McGovern Institute’s Poitras Center for Psychiatric Disorders Research are looking for clues into the origins of the disorder and its symptoms so they can help guide the development of new treatments. Encouragingly, they are beginning to uncover the brain changes that reshape reality for people with schizophrenia.
Genetic clues
Researchers who want to study the root causes of a disease often turn to genetics for clues—and the genetics of schizophrenia are complicated. Hundreds of different genes seem to shape people’s risk of developing the disorder, most of which nudge risk only slightly. For most people, it seems to be the cumulative effect of these genes and how they intersect with other risk factors, like stress and prenatal complications, that determine who develops schizophrenia and who does not.
Gene variants that substantially impact the risk of schizophrenia are expected to reveal more about the underlying biology of the disorder than genes whose individual impact is minor. But these variants are rare, and it took a massive study to find them. In 2022, scientists at the Broad Institute’s Stanley Center for Psychiatric Research reported that after analyzing the DNA of more than 24,000 people with schizophrenia, they had identified mutations in 10 genes that dramatically increased the risk of the disorder.
“I think this is exciting, because for the first time, you can actually have an animal model based onhuman genetics findings,” says McGovern Institute and Stanley Center Investigator Guoping Feng. “You can put these mutations in animal models to try to understand how this mutation affects brain development, circuit formation, circuit function, and behavior.” Feng is also the James W. (1963) and Patricia T. Poitras Professor of Brain and Cognitive Sciences at MIT.
Guoping Feng (right) and his postdoctoral researcher Tinting Zhou (left) examine a mouse brain carrying a genetic mutation associated with schizophrenia. Photo: Steph Stevens
In work supported by the Poitras Center, the Stelling Family Research Fund, and the Yang Tan Collective at MIT, Feng’s lab has engineered three strains of mice that carry ultra-rare schizophrenia-associated mutations. Their first significant findings come from mice with a mutation in a gene called Grin2a. People who inherit a dysfunctional Grin2a gene, which neurons need to detect and respond to a signaling molecule called NMDA, are 20 times more likely to develop schizophrenia than people in whom Grin2a is intact.
Tingting Zhou, a postdoctoral researcher in Feng’s lab, says the team had to think carefully about how to assess mice for schizophrenia-like symptoms. You can’t ask mice about hallucinations or delusions. Instead, Zhou designed an experiment that tested how well mice use new information to update their beliefs about the world—a process that is thought to be impaired in people who experience delusions.
To illustrate how failure to update beliefs can skew someone’s ideas about reality, Zhou describes a situation in which a person watches a stranger reach for something in their pocket, fearing that person intends to harm them. Then, the stranger’s hand emerges with a lollipop. The new information should alleviate concern—but a person with schizophrenia might hold on to their original belief, convinced the lollipop-holding stranger is a threat.
In Zhou’s experiments testing animals’ belief-updating abilities, mice had to keep up with changing information to earn as many treats as possible. Those with the Grin2a mutation were slow to adapt when experimenters adjusted the relative values of their choices. “Once the animal learns something, it’s very hard for them to update the information,” Zhou explains.
Zhou and Feng linked this behavioral difference to abnormally low activity in a part of the brain called the mediodorsal thalamus. The mediodorsal thalamus acts like a switchboard in the brain, routing and coordinating information between different parts of the cortex to support thinking, decision-making, and flexible behavior. Studies with patients have implicated this region in schizophrenia as well, showing that it has fewer cells and is less active in people with the disorder than those without.
The mediodorsal thalamus (pink) is less active in people with schizophrenia and mouse models of the disease. Image: Guoping Feng, Tingting Zhou
Feng’s lab and others are now looking for belief-updating deficits in other genetic models of schizophrenia. “The goal is to look at whether this is a converging mechanism…then you can start to look at what other [brain] regions are involved,” he says.
In mice with Grin2a mutations, the researchers were able to restore normal belief updating by activating neurons in the mediodorsal thalamus, offering hope that manipulating the same circuitry might benefit patients. “It will not be easy,” Feng says, “but at least you have something you can work on. Previously, it was just very hard to imagine how to develop a new therapeutic for schizophrenia.”
Internal noise
It’s not just the genes associated with schizophrenia that differ across affected individuals. The symptoms of the disorder vary, too. People experience some combination of delusions, hallucinations, disorganized speech, and cognitive problems—but none of these are experienced by everyone with the disorder. This heterogeneity complicates the diagnosis, treatment, and study of schizophrenia. For this reason, some researchers are focusing their efforts on understanding its individual symptoms.
Evelina Fedorenko, a McGovern Investigator and associate professor of brain and cognitive sciences, specializes in understanding how the brain processes speech and language. But recently, her group has teamed up with physician-researcher Ann Shinn at McLean Hospital to begin exploring why some people hear voices when no one is speaking.
About three out of four people with schizophrenia experience auditory hallucinations, which most commonly involve voices.
These hallucinations can be distressing, sometimes involving threatening language or commands to cause harm. Some people with mood disorders or post-traumatic stress disorder also hear them.
Tamar Regev was the 2022–2024 Poitras Center Postdoctoral Fellow in Evelina Fedorenko’s lab. Photo: Steph Stevens
To investigate, Tamar Regev, a research scientist in the Fedorenko lab, asked people who experience auditory hallucinations to listen to different kinds of sounds inside an MRI scanner, then compared how their brains responded versus the brains of people without auditory hallucinations. Her study included participants with schizophrenia and bipolar disorder, both with and without a history of auditory hallucinations, as well as healthy controls.
Inside the scanner, participants listened to three kinds of audio: spoken language, gibberish, and gibberish so scrambled that it barely resembled speech. Regev analyzed how these sounds impacted activity in areas the brain uses to process auditory input at different levels: a part of the auditory cortex that is sensitive to all sounds; a higher-level region within the auditory cortex that usually responds to anything that sounds like speech, even if its content is unclear; and the brain’s language-processing network, which is called on to understand the content of speech, as well as written or signed communications.
Regev found that in people with hallucinations, the part of the brain that usually responds only to language responded to meaningless speech as well. “In this pathway from auditory to speech to language processing, the stimuli that should be filtered out somewhere on the way are now passing to higher stations,” she explains. While auditory hallucinations don’t require external sounds, Fedorenko and Regev propose that the brain’s language areas might be similarly activated by “internal noise” in auditory circuits.
Scrambled language
In people who experience auditory hallucinations, the brain’s language regions respond to sounds that aren’t language–including scrambled meaningless gibberish. Below is a sample gibberish clip used in Fedorenko’s study.
Early identification
McGovern scientists have also used brain imaging to investigate what happens in the brain before people develop clear symptoms of schizophrenia. The disorder is usually diagnosed in adolescence or young adulthood, when patients exhibit the first signs of psychosis—but its origins in the brain likely take root years before that.
“One of the things we’re super interested in is, can you identify people at risk early on, before they have a big problem,” says McGovern Investigator John Gabrieli, whose work is also supported by the Poitras Center and the Stelling Family Research Fund. That might give clinicians an opportunity to intervene and lessen or prevent the disorder’s most devastating effects, he says.
Gabrieli and his colleagues have studied the brains of children who, because they have a parent or sibling with schizophrenia, have an elevated risk of developing the disorder themselves. They found that a system called the default mode network (DMN), which is overactive in adults with schizophrenia, is already working overtime when children in this high-risk group are seven- to 12-years-old.
Gabrieli explains that the DMN is active when people are not actively engaged in an activity or thinking about the external world. “It turns on when you think about your family, your values, your hopes for the future, or important events of your life. It’s almost like a system of who /you are,” he says. Hallucinations and delusions experienced by people with schizophrenia may be associated with overactivity in this network.
The default mode network (DMN) is a large-scale brain network that is active when a person is not focused on the outside world and the brain is at wakeful rest. The DMN is often over-engaged in adolescents with depression and anxiety, as well as teens at risk for these and other disorders like schizophrenia (left). DMN activation and connectivity can be “tuned” to a healthier state through the practice of mindfulness (right).
“They’re kind of living in their internal world of beliefs, as opposed to the reality that most of us occupy,” Gabrieli explains.
He and his colleagues think overactivity in the DMN might make people vulnerable to schizophrenia—and their data show this atypical activity can be detected many years before the core symptoms of schizophrenia appear. With further validation, children with hyperactivity of the DMN might be candidates for early intervention.
With new and better interventions, the ability to identify people who may be on a path toward schizophrenia will be even more impactful—underscoring the need for continued research on multiple fronts. A recent gift of $8 million to the Poitras Center from Patricia and James Poitras is helping accelerate this work in labs at the McGovern Institute and beyond.
One of the symptoms of schizophrenia is difficulty incorporating new information about the world. This can lead patients to struggle with making decisions and, eventually, to lose touch with reality.
MIT neuroscientists have now identified a gene mutation that appears to give rise to this type of difficulty. In a study of mice, the researchers found that the mutated gene impairs the function of a brain circuit that is responsible for updating beliefs based on new input.
This mutation, in a gene called grin2a, was originally identified in a large-scale screen of patients with schizophrenia. The new study suggests that drugs targeting this brain circuit could help with some of the cognitive impairments seen in schizophrenia patients.
“If this circuit doesn’t work well, you cannot quickly integrate information,” says Guoping Feng, the James W. and Patricia T. Poitras Professor in Brain and Cognitive Sciences at MIT, a member of the Broad Institute of Harvard and MIT, and the associate director of the McGovern Institute for Brain Research at MIT. “We are quite confident this circuit is one of the mechanisms that contributes to the cognitive impairment that is a major part of the pathology of schizophrenia.”
Feng and Michael Halassa, an associate professor of psychiatry and neuroscience at Tufts University, are the senior authors of the new study, which appears today in Nature Neuroscience. Tingting Zhou, a research scientist at the McGovern Institute, and Yi-Yun Ho, a former MIT postdoc, are the lead authors of the paper.
McGovern Institute Investigator Guoping Feng (right) and his postdoctoral researcher Tinting Zhou (left) in the lab. Photo: Steph Stevens
Adapting to new information
Schizophrenia is known to have a strong genetic component. For the general population, the risk of developing the disease is about 1 percent, but that goes up to 10 percent for those who have a parent or sibling with the disease, and 50 percent for people who have an identical twin with the disease.
Researchers at the Stanley Center for Psychiatric Research at the Broad Institute have identified more than 100 gene variants linked to schizophrenia, using genome-wide association studies. However, many of those variants are located in non-coding regions of the genome, making it difficult to figure out how they might influence development of the disease.
More recently, researchers at the Stanley Center used a different strategy, known as whole-exome sequencing, to reveal gene mutations linked to schizophrenia. This technique sequences only the protein-coding regions of the genome, so it can reveal mutations that are located in known genes.
Using this approach on about 25,000 sequences from people with schizophrenia and 100,000 sequences from control subjects, the researchers identified 10 genes in which mutations significantly increase the risk of developing schizophrenia.
In the new Nature Neuroscience study, Feng and his students created a mouse model with a mutation in one of those genes, grin2a. This gene encodes a protein that forms part of the NMDA receptor — a receptor that is activated by the neurotransmitter glutamate and is often found on the surface of neurons.
Zhou then investigated whether these mice displayed any of the characteristic behaviors seen in schizophrenia patients. These patients show many complex symptoms, including psychoses such as hallucinations and delusions (loss of contact with reality). Those are difficult to study in mice, but it is possible to study related symptoms such as difficulty in interpreting new sensory input.
Over the past two decades, schizophrenia researchers have hypothesized that psychosis may stem from an impaired ability to update beliefs based on new information.
“Our brain can form a prior belief of reality, and when sensory input comes into the brain, a neurotypical brain can use this new input to update the prior belief. This allows us to generate a new belief that’s close to what the reality is,” Zhou says. “What happens in schizophrenia patients is that they weigh too heavily on the prior belief. They don’t use as much current input to update what they believed before, so the new belief is detached from reality.”
To study this, Zhou designed an experiment that required mice to choose between two levers to press to earn a food reward. One lever was low-reward — mice had to push it six times to get one drop of milk. A high-reward lever dispensed three drops per push.
At the beginning of the study, all of the mice learned to prefer the high-reward lever. However, as the experiment went on, the number of presses required to dispense the higher reward gradually went up, while there were no changes to the low-reward lever.
As the effort required went up, healthy mice start to switch back and forth between the two levers. Once they had to press the high-reward lever around 18 times for three drops of milk, making the effort per drop about the same for each lever, they eventually switched permanently to the low-reward lever. However, mice with a mutation in grin2a showed a different behavior pattern. They spent more time switching back and forth between the two levers, and they made the switch to the low-reward side much later.
“We find that neurotypical animals make adaptive decisions in this changing environment,” Zhou says. “They can switch from the high-reward side to the low-reward side around the equal value point, while for the animals with the mutation, the switch happens much later. Their adaptive decision-making is much slower compared to the wild-type animals.”
An impaired circuit
Using functional ultrasound imaging and electrical recordings, the researchers found that the brain region affected most by the grin2a mutation was the mediodorsal thalamus. This part of the brain connects with the prefrontal cortex to form a thalamocortical circuit that is responsible for regulating cognitive functions such as executive control and decision-making.
The researchers found that neuronal activity in the mediodorsal thalamus appears to keep track of the changes in value of the two reward options. Additionally, the mice showed different patterns of neural activity depending on which state they were — either an exploratory state or committed to one side.
The researchers also showed that they could use optogenetics to reverse the behavioral symptoms of the mice with mutated grin2a. They engineered the neurons of the mediodorsal thalamus so that they could be activated by light, and when these neurons were activated, the mice began behaving similarly to mice without the grin2a mutation.
While only a very small percentage of schizophrenia patients have mutations in the grin2a gene, it’s possible that this circuit dysfunction is a converging mechanism of cognitive impairment for a subset of schizophrenia patients with different causes.
Targeting this circuit could offer a way to overcome some of the cognitive impairments seen in schizophrenia patients, the researchers say. To do that, they are now working on identifying targets within the circuit that could be potentially druggable.
The research was funded by the National Institutes of Mental Health, the Poitras Center for Psychiatric Disorders Research at MIT, the Yang Tan Collective at MIT, the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics at MIT, the Stelling Family Research Fund at MIT, the Stanley Center for Psychiatric Research, and the Brain and Behavior Research Foundation.
When it comes to brain function, neurons get a lot of the glory. But healthy brains depend on the cooperation of many kinds of cells. The most abundant of the brain’s non-neuronal cells are astrocytes, star-shaped cells with a lot of responsibilities. Astrocytes help shape neural circuits, participate in information processing, and provide nutrient and metabolic support to neurons. Individual cells can take on new roles throughout their lifetimes, and at any given time, the astrocytes in one part of the brain will look and behave differently than the astrocytes somewhere else.
After an extensive analysis by scientists at MIT’s McGovern Institute, neuroscientists now have an atlas detailing astrocytes’ dynamic diversity. Its maps depict the regional specialization of astrocytes across the brains of both mice and marmosets—two powerful models for neuroscience research—and show how their populations shift as brains develop, mature, and age. The study, reported in the November 20 issue of the journal Neuron, was led by Guoping Feng, the James W. (1963) and Patricia T. Poitras Professor of Brain and Cognitive Sciences at MIT. This work was supported by the Hock E. Tan and K. Lisa Yang Center for Autism Research, part of the Yang Tan Collective at MIT, and the National Institutes of Health’s BRAIN Initiative.
Probing the unknown
“It’s really important for us to pay attention to non-neuronal cells’ role in health and disease,” says Feng, who is also the associate director of the McGovern Institute, the director of the Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, and a member of the Broad Institute of MIT and Harvard. And indeed, these cells—once seen as merely supporting players—have gained more of the spotlight in recent years. Astrocytes are known to play vital roles in the brain’s development and function, and their dysfunction seems to contribute to many psychiatric disorders and neurodegenerative diseases. “But compared to neurons, we know a lot less—especially during development,” Feng adds.
Feng and Margaret Schroeder, a former graduate student in his lab, thought it was important to understand astrocyte diversity across three axes: space, time, and species. They knew from earlier work in the lab, done in collaboration with Steve McCarroll’s lab at Harvard and led by Fenna Krienen in his group, that in adult animals, different parts of the brain have distinctive sets of astrocytes.
“The natural question was, how early in development do we think this regional patterning of astrocytes starts?” Schroeder says.
To find out, she and her colleagues collected brain cells from mice and marmosets at six stages of life, spanning embryonic development to old age. For each animal, they sampled cells from four different brain regions: the prefrontal cortex, the motor cortex, the striatum, and the thalamus.
Then, working with Krienen, who is now an assistant professor at Princeton University, they analyzed the molecular contents of those cells, creating a profile of genetic activity for each one. That profile was based on the mRNA copies of genes found inside the cell, which are known collectively as the cell’s transcriptome. Determining which genes a cell is using and how active those genes are gives researchers insight into a cell’s function and is one way of defining its identity.
Dynamic diversity
After assessing the transcriptomes of about 1.4 million brain cells, the group focused in on the astrocytes, analyzing and comparing their patterns of gene expression. At every life stage, from before birth to old age, the team found regional specialization: Astrocytes from different brain regions had similar patterns of gene expression, which were distinct from those of astrocytes in other brain regions.
This regional specialization was also apparent in the distinct shapes of astrocytes in different parts of the brain, which the team was able to see with expansion microscopy, a high-resolution imaging method developed by McGovern colleague Edward Boyden that reveals fine cellular features.
Notably, the astrocytes in each region changed as animals matured. “When we looked at our late embryonic time point, the astrocytes were already regionally patterned. But when we compare that to the adult profiles, they had completely shifted again,” Schroeder says. “So there’s something happening over postnatal development.” The most dramatic changes the team detected occurred between birth and early adolescence, a period during which brains rapidly rewire as animals begin to interact with the world and learn from their experiences.
Maps generated by Feng’s team depict the regional specialization of astrocytes across the brains of both mice and marmosets—two powerful models for neuroscience research—and show how their populations shift as brains develop, mature, and age.
Feng and Schroeder suspect that the changes they observed may be driven by the neural circuits that are sculpted and refined as the brain matures. “What we think they’re doing is kind of adapting to their local neuronal niche,” Schroeder says. “The types of genes that they are upregulating and changing during development points to their interaction with neurons.” Feng adds that astrocytes may change their genetic programs in response to nearby neurons, or alternatively, they might help direct the development or function of local circuits as they adopt identities best suited to support particular neurons.
Both mouse and marmoset brains exhibited regional specialization of astrocytes and changes in those populations over time. But when the researchers looked at the specific genes whose activity defined various astrocyte populations, the data from the two species diverged. Schroeder calls this a note of caution for scientists who study astrocytes in animal models, and adds that the new atlas will help researchers assess the potential relevance of findings across species.
Beyond astrocytes
With a new understanding of astrocyte diversity, Feng says his team will pay close attention to how these cells are impacted by the disease-related genes they study and how those effects change during development. He also notes that the gene expression data in the atlas can be used to predict interactions between astrocytes and neurons. “This will really guide future experiments: how these cells’ interactions can shift with changes in the neurons or changes in the astrocytes,” he says.
The Feng lab is eager for other researchers to take advantage of the massive amounts of data they generated as they produced their atlas. Schroeder points out that the team analyzed the transcriptomes of all kinds of cells in the brain regions they studied, not just astrocytes. They are sharing their findings so researchers can use them to understand when and where specific genes are used in the brain, or dig in more deeply to further to explore the brain’s cellular diversity.
More than 300 million people worldwide are living with rare disorders — many of which have a genetic cause and affect the brain and nervous system — yet the vast majority of these conditions lack an approved therapy. Because each rare disorder affects fewer than 65 out of every 100,000 people, studying these disorders and creating new treatments for them is especially challenging.
Thanks to a generous philanthropic gift from Ana Méndez ’91 and Rajeev Jayavant ’86, EE ’88, SM ’88, MIT is now poised to fill the gaps in this research landscape. By establishing the Rare Brain Disorders Nexus — or RareNet — at MIT’s McGovern Institute, the alumni aim to convene leaders in neuroscience research, clinical medicine, patient advocacy, and industry to streamline the lab-to-clinic pipeline for rare brain disorder treatments.
“Ana and Rajeev’s commitment to MIT will form crucial partnerships to propel the translation of scientific discoveries into promising therapeutics and expand the Institute’s impact on the rare brain disorders community,” says MIT President Sally Kornbluth. “We are deeply grateful for their pivotal role in advancing such critical science and bringing attention to conditions that have long been overlooked.”
Building new coalitions
Several hurdles have slowed the lab-to-clinic pipeline for rare brain disorder research. It is difficult to secure a sufficient number of patients per study, and current research efforts are fragmented since each study typically focuses on a single disorder (there are more than 7,000 known rare disorders, according to the World Health Organization). Pharmaceutical companies are often reluctant to invest in emerging treatments due to a limited market size and the high costs associated with preparing drugs for commercialization.
Méndez and Jayavant envision that RareNet will finally break down these barriers. “Our hope is that RareNet will allow leaders in the field to come together under a shared framework and ignite scientific breakthroughs across multiple conditions. A discovery for one rare brain disorder could unlock new insights that are relevant to another,” says Jayavant. “By congregating the best minds in the field, we are confident that MIT will create the right scientific climate to produce drug candidates that may benefit a spectrum of uncommon conditions.”
Guoping Feng, the James W. (1963) and Patricia T. Poitras Professor in Neuroscience and associate director of the McGovern Institute for Brain Research at MIT, will serve as RareNet’s inaugural faculty director. Feng holds a strong record of advancing studies on therapies for neurodevelopmental disorders, including autism spectrum disorders, Williams syndrome, and uncommon forms of epilepsy. His team’s gene therapy for Phelan-McDermid syndrome, a rare and profound autism spectrum disorder, has been licensed to Jaguar Gene Therapy and is currently undergoing clinical trials. “RareNet pioneers a unique model for biomedical research — one that is reimagining the role academia can play in developing therapeutics,” says Feng.
An early version of a gene therapy for SHANK3 mutations — linked to a rare brain disorder called Phelan-McDermid syndrome — correctly finds its way to neurons. Image: Feng lab
RareNet plans to deploy two major initiatives: a global consortium and a therapeutic pipeline accelerator. The consortium will form an international network of researchers, clinicians, and patient groups from the outset. It seeks to connect siloed research efforts, secure more patient samples, promote data sharing, and drive a strong sense of trust and goal alignment across the RareNet community. Partnerships within the consortium will support the aim of the therapeutic pipeline accelerator: to de-risk early lab discoveries and expedite their translation to clinic. By fostering more targeted collaborations — especially between academia and industry — the accelerator will prepare potential treatments for clinical use as efficiently as possible.
MIT labs are focusing on four uncommon conditions in the first wave of RareNet projects: Rett syndrome, prion disease, disorders linked to SYNGAP1 mutations, and Sturge-Weber syndrome. The teams are working to develop novel therapies that can slow, halt, or reverse dysfunctions in the brain and nervous system.
These efforts will build new bridges to connect key stakeholders across the rare brain disorders community and disrupt conventional research approaches. “Rajeev and I are motivated to seed powerful collaborations between MIT researchers, clinicians, patients, and industry,” says Méndez. “Guoping Feng clearly understands our goal to create an environment where foundational studies can thrive and seamlessly move toward clinical impact.”
“Patient and caregiver experiences, and our foreseeable impact on their lives, will guide us and remain at the forefront of our work,” Feng adds. “For far too long the rare brain disorders community has been deprived of life-changing treatments — and, importantly, hope. RareNet gives us the opportunity to transform how we study these conditions and to do so at a moment when it’s needed more than ever.”
One in every eight people—970 million globally—live with mental illness, according to the World Health Organization, with depression and anxiety being the most common mental health conditions worldwide. Existing therapies for complex psychiatric disorders like depression, anxiety, and schizophrenia have limitations, and federal funding to address these shortcomings is growing increasingly uncertain.
James and Patricia Poitras at an event co-hosted by the McGovern Institute and Autism Speaks. Photo: Justin Knight
Patricia and James Poitras ’63 have committed $8 million to the Poitras Center for Psychiatric Disorders Research to launch pioneering research initiatives aimed at uncovering the brain basis of major mental illness and accelerating the development of novel treatments.
“Federal funding rarely supports the kind of bold, early-stage research that has the potential to transform our understanding of psychiatric illness. Pat and I want to help fill that gap—giving researchers the freedom to follow their most promising leads, even when the path forward isn’t guaranteed,” says James Poitras, who is chair of the McGovern Institute Board.
Their latest gift builds upon their legacy of philanthropic support for psychiatric disorders research at MIT, which now exceeds $46 million.
“With deep gratitude for Jim and Pat’s visionary support, we are eager to launch a bold set of studies aimed at unraveling the neural and cognitive underpinnings of major mental illnesses,” says Robert Desimone, director of the McGovern Institute, home to the Poitras Center. “Together, these projects represent a powerful step toward transforming how we understand and treat mental illness.”
A legacy of support
Soon after joining the McGovern Institute Leadership Board in 2006, the Poitrases made a $20 million commitment to establish the Poitras Center for Psychiatric Disorders Research at MIT. The center’s goal, to improve human health by addressing the root causes of complex psychiatric disorders, is deeply personal to them both.
“We had decided many years ago that our philanthropic efforts would be directed towards psychiatric research. We could not have imagined then that this perfect synergy between research at MIT’s McGovern Institute and our own philanthropic goals would develop,” recalls Patricia.
The center supports research at the McGovern Institute and collaborative projects with institutions such as the Broad Institute, McLean Hospital, Mass General Brigham and other clinical research centers. Since its establishment in 2007, the center has enabled advances in psychiatric research including the development of a machine learning “risk calculator” for bipolar disorder, the use of brain imaging to predict treatment outcomes for anxiety, and studies demonstrating that mindfulness can improve mental health in adolescents.
Feng Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT, delivers a lecture at the Poitras Center’s 10th anniversary celebration in 2017. Photo: Justin Knight
For the past decade, the Poitrases have also fueled breakthroughs in McGovern Investigator Feng Zhang’s lab, backing the invention of powerful CRISPR systems and other molecular tools that are transforming biology and medicine. Their support has enabled the Zhang team to engineer new delivery vehicles for gene therapy, including vehicles capable of carrying genetic payloads that were once out of reach. The lab has also advanced innovative RNA-guided gene engineering tools such as NovaIscB, published in Nature Biotechnology in May 2025. These revolutionary genome editing and delivery technologies hold promise for the next generation of therapies needed for serious psychiatric illness.
In addition to fueling research in the center, the Poitras family has gifted two endowed professorships—the James and Patricia Poitras Professor of Neuroscience at MIT, currently held by Feng Zhang, and the James W. (1963) and Patricia T. Poitras Professor of Brain and Cognitive Sciences at MIT, held by Guoping Feng—and an annual postdoctoral fellowship at the McGovern Institute.
New initiatives at the Poitras Center
The Poitras family’s latest commitment to the Poitras Center will launch an ambitious set of new projects that bring together neuroscientists, clinicians, and computational experts to probe underpinnings of complex psychiatric disorders including schizophrenia, anxiety, and depression. These efforts reflect the center’s core mission: to speed scientific discovery and therapeutic innovation in the field of psychiatric brain disorders research.
McGovern cognitive neuroscientists Evelina Fedorenko PhD ‘07 and Nancy Kanwisher ’80, PhD ’86, the Walter A. Rosenblith Professor of Cognitive Neuroscience—in collaboration with psychiatrist Ann Shinn of McLean Hospital—will explore how altered inner speech and reasoning contribute to the symptoms of schizophrenia. They will collect functional MRI data from individuals diagnosed with schizophrenia and matched controls as they perform reasoning tasks. The goal is to identify the brain activity patterns that underlie impaired reasoning in schizophrenia, a core cognitive disruption in the disorder.
Patricia Poitras (center) with McGovern Investigators Nancy Kanwisher ’80, PhD ’86 (left) and Martha Constantine-Paton (right) at the Poitras Center’s 10th anniversary celebration in 2017. Photo: Justin Knight
A complementary line of investigation will focus on the role of inner speech—the “voice in our head” that shapes thought and self-awareness. The team will conduct a large-scale online behavioral study of neurotypical individuals to analyze how inner speech characteristics correlate with schizophrenia-spectrum traits. This will be followed by neuroimaging work comparing brain architecture among individuals with strong or weak inner voices and people with schizophrenia, with the aim of discovering neural markers linked to self-talk and disrupted cognition.
A different project led by McGovern neuroscientist Mark Harnett and 2024–2026 Poitras Center Postdoctoral Fellow Cynthia Rais focuses on how ketamine—an increasingly used antidepressant—alters brain circuits to produce rapid and sustained improvements in mood. Despite its clinical success, ketamine’s mechanisms of action remain poorly understood. The Harnett lab is using sophisticated tools to track how ketamine affects synaptic communication and large-scale brain network dynamics, particularly in models of treatment-resistant depression. By mapping these changes at both the cellular and systems levels, the team hopes to reveal how ketamine lifts mood so quickly—and inform the development of safer, longer-lasting antidepressants.
Guoping Feng is leveraging a new animal model of depression to uncover the brain circuits that drive major depressive disorder. The new animal model provides a powerful system for studying the intricacies of mood regulation. Feng’s team is using state-of-the-art molecular tools to identify the specific genes and cell types involved in this circuit, with the goal of developing targeted treatments that can fine-tune these emotional pathways.
“This is one of the most promising models we have for understanding depression at a mechanistic level,” says Feng, who is also associate director of the McGovern Institute. “It gives us a clear target for future therapies.”
Another novel approach to treating mood disorders comes from the lab of James DiCarlo, the Peter de Florez Professor of Neuroscience at MIT, who is exploring the brain’s visual-emotional interface as a therapeutic tool for anxiety. The amygdala, a key emotional center in the brain, is heavily influenced by visual input. DiCarlo’s lab is using advanced computational models to design visual scenes that may subtly shift emotional processing in the brain—essentially using sight to regulate mood. Unlike traditional therapies, this strategy could offer a noninvasive, drug-free option for individuals suffering from anxiety.
Together, these projects exemplify the kind of interdisciplinary, high-impact research that the Poitras Center was established to support.
“Mental illness affects not just individuals, but entire families who often struggle in silence and uncertainty,” adds Patricia. “Our hope is that Poitras Center scientists will continue to make important advancements and spark novel treatments for complex mental health disorders and most of all, give families living with these conditions a renewed sense of hope for the future.”
The National Academy of Sciences has elected 120 members and 24 international members, including five faculty members from MIT. Guoping Feng, Piotr Indyk, Daniel J. Kleitman, Daniela Rus, and Senthil Todadri were elected in recognition of their “distinguished and continuing achievements in original research.” Membership to the National Academy of Sciences is one of the highest honors a scientist can receive in their career.
Among the new members added this year are also nine MIT alumni, including Zvi Bern ’82; Harold Hwang ’93, SM ’93; Leonard Kleinrock SM ’59, PhD ’63; Jeffrey C. Lagarias ’71, SM ’72, PhD ’74; Ann Pearson PhD ’00; Robin Pemantle PhD ’88; Jonas C. Peters PhD ’98; Lynn Talley PhD ’82; and Peter T. Wolczanski ’76. Those elected this year bring the total number of active members to 2,617, with 537 international members.
The National Academy of Sciences is a private, nonprofit institution that was established under a congressional charter signed by President Abraham Lincoln in 1863. It recognizes achievement in science by election to membership, and — with the National Academy of Engineering and the National Academy of Medicine — provides science, engineering, and health policy advice to the federal government and other organizations.
Guoping Feng
Guoping Feng is the James W. (1963) and Patricia T. Poitras Professor in the Department of Brain and Cognitive Sciences. He is also associate director and investigator in the McGovern Institute for Brain Research, a member of the Broad Institute of MIT and Harvard, and director of the Hock E. Tan and K. Lisa Yang Center for Autism Research.
His research focuses on understanding the molecular mechanisms that regulate the development and function of synapses, the places in the brain where neurons connect and communicate. He’s interested in how defects in the synapses can contribute to psychiatric and neurodevelopmental disorders. By understanding the fundamental mechanisms behind these disorders, he’s producing foundational knowledge that may guide the development of new treatments for conditions like obsessive-compulsive disorder and schizophrenia.
Feng received his medical training at Zhejiang University Medical School in Hangzhou, China, and his PhD in molecular genetics from the State University of New York at Buffalo. He did his postdoctoral training at Washington University at St. Louis and was on the faculty at Duke University School of Medicine before coming to MIT in 2010. He is a member of the American Academy of Arts and Sciences, a fellow of the American Association for the Advancement of Science, and was elected to the National Academy of Medicine in 2023.
Piotr Indyk
Piotr Indyk is the Thomas D. and Virginia W. Cabot Professor of Electrical Engineering and Computer Science. He received his magister degree from the University of Warsaw and his PhD from Stanford University before coming to MIT in 2000.
Indyk’s research focuses on building efficient, sublinear, and streaming algorithms. He’s developed, for example, algorithms that can use limited time and space to navigate massive data streams, that can separate signals into individual frequencies faster than other methods, and can address the “nearest neighbor” problem by finding highly similar data points without needing to scan an entire database. His work has applications on everything from machine learning to data mining.
He has been named a Simons Investigator and a fellow of the Association for Computer Machinery. In 2023, he was elected to the American Academy of Arts and Sciences.
Daniel J. Kleitman
Daniel Kleitman, a professor emeritus of applied mathematics, has been at MIT since 1966. He received his undergraduate degree from Cornell University and his master’s and PhD in physics from Harvard University before doing postdoctoral work at Harvard and the Niels Bohr Institute in Copenhagen, Denmark.
Kleitman’s research interests include operations research, genomics, graph theory, and combinatorics, the area of math concerned with counting. He was actually a professor of physics at Brandeis University before changing his field to math, encouraged by the prolific mathematician Paul Erdős. In fact, Kleitman has the rare distinction of having an Erdős number of just one. The number is a measure of the “collaborative distance” between a mathematician and Erdős in terms of authorship of papers, and studies have shown that leading mathematicians have particularly low numbers.
He’s a member of the American Academy of Arts and Sciences and has made important contributions to the MIT community throughout his career. He was head of the Department of Mathematics and served on a number of committees, including the Applied Mathematics Committee. He also helped create web-based technology and an online textbook for several of the department’s core undergraduate courses. He was even a math advisor for the MIT-based film “Good Will Hunting.”
Daniela Rus
Daniela Rus, the Andrew (1956) and Erna Viterbi Professor of Electrical Engineering and Computer Science, is the director of the Computer Science and Artificial Intelligence Laboratory (CSAIL). She also serves as director of the Toyota-CSAIL Joint Research Center.
Her research on robotics, artificial intelligence, and data science is geared toward understanding the science and engineering of autonomy. Her ultimate goal is to create a future where machines are seamlessly integrated into daily life to support people with cognitive and physical tasks, and deployed in way that ensures they benefit humanity. She’s working to increase the ability of machines to reason, learn, and adapt to complex tasks in human-centered environments with applications for agriculture, manufacturing, medicine, construction, and other industries. She’s also interested in creating new tools for designing and fabricating robots and in improving the interfaces between robots and people, and she’s done collaborative projects at the intersection of technology and artistic performance.
Rus received her undergraduate degree from the University of Iowa and her PhD in computer science from Cornell University. She was a professor of computer science at Dartmouth College before coming to MIT in 2004. She is part of the Class of 2002 MacArthur Fellows; was elected to the National Academy of Engineering and the American Academy of Arts and Sciences; and is a fellow of the Association for Computer Machinery, the Institute of Electrical and Electronics Engineers, and the Association for the Advancement of Artificial Intelligence.
Senthil Todadri
Senthil Todadri, a professor of physics, came to MIT in 2001. He received his undergraduate degree from the Indian Institute of Technology in Kanpur and his PhD from Yale University before working as a postdoc at the Kavli Institute for Theoretical Physics in Santa Barbara, California.
Todadri’s research focuses on condensed matter theory. He’s interested in novel phases and phase transitions of quantum matter that expand beyond existing paradigms. Combining modeling experiments and abstract methods, he’s working to develop a theoretical framework for describing the physics of these systems. Much of that work involves understanding the phenomena that arise because of impurities or strong interactions between electrons in solids that don’t conform with conventional physical theories. He also pioneered the theory of deconfined quantum criticality, which describes a class of phase transitions, and he discovered the dualities of quantum field theories in two dimensional superconducting states, which has important applications to many problems in the field.
Todadri has been named a Simons Investigator, a Sloan Research Fellow, and a fellow of the American Physical Society. In 2023, he was elected to the American Academy of Arts and Sciences
McGovern Institute Director Robert Desimone. Photo: Steph Stevens
As we start 2024, I hope you can join me in celebrating a historic recent advance: the FDA approval of Casgevy, a bold new treatment for devastating sickle cell disease and the world’s first approved CRISPR gene therapy.
Developed by Vertex Pharmaceuticals and CRISPR Therapeutics, we are proud to share that this pioneering therapy licenses the CRISPR discoveries of McGovern scientist and Poitras Professor of Neuroscience Feng Zhang.
It is amazing to think that Feng’s breakthrough work adapting CRISPR-Cas9 for genome editing in eukaryotic cells was published only 11 years ago today in Science.
Incredibly, CRISPR-Cas9 rapidly transitioned from proof-of-concept experiments to an approved treatment in just over a decade.
McGovern scientists are determined to maintain the momentum!
Incredibly, CRISPR-Cas9 rapidly transitioned from proof-of-concept experiments to an approved treatment in just over a decade.
Our labs are creating new gene therapies that are already in clinical trials or preparing to enroll patients in trials. For instance, Feng Zhang’s team has developed therapies currently in clinical trials for lymphoblastic leukemia and beta thalassemia, while another McGovern researcher, Guoping Feng, the Poitras Professor of Brain and Cognitive Sciences at MIT, has made advancements that lay the groundwork for a new gene therapy to treat a severe form of autism spectrum disorder. It is expected to enter clinical trials later this year. Moreover, McGovern fellows Omar Abudayyeh and Jonathan Gootenberg created programmable genomic tools that are now licensed for use in monogenic liver diseases and autoimmune disorders.
These exciting innovations stem from your steadfast support of our high-risk, high-reward research. Your generosity is enabling our scientists to pursue basic research in other areas with potential therapeutic applications in the future, such as mechanisms of pain, addiction, the connections between the brain and gut, the workings of memory and attention, and the bi-directional influence of artificial intelligence on brain research. All of this fundamental research is being fueled by major new advances in technology, many of them developed here.
As we enter a new year filled with anticipation following our inaugural gene therapy, I want to express my heartfelt gratitude for your invaluable support in advancing our research programs. Your role in pushing our research to new heights is valued by all faculty, students, and researchers at the McGovern Institute. We can’t wait to share our continued progress with you.
Thank you again for partnering with us to make great scientific achievements possible.
With appreciation and best wishes,
Robert Desimone, PhD
Director, McGovern Institute
Doris and Don Berkey Professor of Neuroscience, MIT
Funded by philanthropist Lisa Yang, the K. Lisa Yang Postbaccalaureate Scholar Program provides two years of paid laboratory experience, mentorship, and education to recent college graduates from backgrounds underrepresented in neuroscience. This year, two young researchers in McGovern Institute labs, Joseph Itiat and Sam Merrow, are the recipients of the Yang postbac program.
Itiat moved to the United States from Nigeria in 2019 to pursue a degree in psychology and cognitive neuroscience at Temple University. Today, he is a Yang postbac in John Gabrieli’s lab studying the relationship between learning and value processes and their influence on future-oriented decision-making. Ultimately, Itiat hopes to develop models that map the underlying mechanisms driving these processes.
“Being African, with limited research experience and little representation in the domain of neuroscience research,” Itiat says, “I chose to pursue a postbaccalaureate
research program to prepare me for a top graduate school and a career in cognitive neuroscience.”
Merrow first fell in love with science while working at the Barrow Neurological Institute in Arizona during high school. After graduating from Simmons University in Boston, Massachusetts, Merrow joined Guoping Feng’s lab as a Yang postbac to pursue research on glial cells and brain disorders. “As a queer, nonbinary, LatinX person, I have not met anyone like me in my field, nor have I had role models that hold a similar identity to myself,” says Merrow.
“My dream is to one day become a professor, where I will be able to show others that science is for anyone.”
Previous Yang postbacs include Alex Negron, Zoe Pearce, Ajani Stewart, and Maya Taliaferro.
