Author: MIT News

Five with MIT ties elected to the National Academy of Medicine for 2021

by Julie Pryor |

The National Academy of Medicine (NAM) has announced the election of 100 new members for 2021, including two MIT faculty members and three additional Institute affiliates.

Faculty honorees include Linda G. Griffith, a professor in the MIT departments of Biological Engineering and Mechanical Engineering; and Feng Zhang, a professor in the MIT departments of Brain and Cognitive Sciences and Biological Engineering. Guillermo Antonio Ameer SCD ’99, a professor of biomedical engineering and surgery at Northwestern University; Darrell Gaskin SM ’87, a professor of health policy and management at Johns Hopkins University; and Vamsi Mootha, an institute member of the Broad Institute of MIT and Harvard and former student in the Harvard-MIT Program in Health Sciences and Technology, were also honored.

The new inductees were elected through a process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care, and public health. Election to the academy is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.

Griffith, the School of Engineering Professor of Teaching Innovation and director of the Center for Gynepathology Research at MIT, is credited for her longstanding leadership in research, education, and medical translation. Specifically, the NAM recognizes her pioneering work in tissue engineering, biomaterials, and systems biology, including the development of the first “liver chip” technology. Griffith is also recognized for inventing 3D biomaterials printing and organotypic models for systems gynopathology, and for the establishment of the biological engineering department at MIT.

The academy recognizes Zhang, the Patricia and James Poitras ’63 Professor in Neuroscience at MIT, for revolutionizing molecular biology and powering transformative leaps forward in our ability to study and treat human diseases. Zhang, who also is an investigator at the Howard Hughes Medical Institute and the McGovern Institute for Brain Research, and a core member of the Broad Institute of MIT and Harvard, is specifically credited for the discovery of novel microbial enzymes and their development as molecular technologies, including optogenetics and CRISPR-mediated genome editing. The academy also commends Zhang for his outstanding mentoring and professional services.

Ameer, the Daniel Hale Williams Professor of Biomedical Engineering and Surgery at the Northwestern University Feinberg School of Medicine, earned his Doctor of Science degree from the MIT Department of Chemical Engineering in 1999. A professor of biomedical engineering and of surgery who is also the director of the Center for Advanced Regenerative Engineering, he is cited by the NAM “For pioneering contributions to regenerative engineering and medicine through the development, dissemination, and translation of citrate-based biomaterials, a new class of biodegradable polymers that enabled the commercialization of innovative medical devices approved by the U.S. Food and Drug Administration for use in a variety of surgical procedures.”

Gaskin, the William C. and Nancy F. Richardson Professor in Health Policy and Management, Bloomberg School of Public Health at Johns Hopkins University, earned his Master of Science degree from the MIT Department of Economics in 1987. A health economist who advances community, neighborhood, and market-level policies and programs that reduce health disparities, he is cited by the NAM “For his work as a leading health economist and health services researcher who has advanced fundamental understanding of the role of place as a driver in racial and ethnic health disparities.”

Mootha, the founding co-director of the Broad Institute’s Metabolism Program, is a professor of systems biology and medicine at Harvard Medical School and a professor in the Department of Molecular Biology at Massachusetts General Hospital. An alumnus of the Harvard-MIT Program in Health Sciences and Technology and former postdoc with the Whitehead Institute for Biomedical Research, Mootha is an expert in the mitochondrion, the “powerhouse of the cell,” and its role in human disease. The NAM cites Mootha “For transforming the field of mitochondrial biology by creatively combining modern genomics with classical bioenergetics.”

Established in 1970 by the National Academy of Sciences, the NAM addresses critical issues in health, science, medicine, and related policy and inspires positive actions across sectors. NAM works alongside the National Academy of Sciences and National Academy of Engineering to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies of Sciences, Engineering, and Medicine also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding of STEMM. With their election, NAM members make a commitment to volunteer their service in National Academies activities.

Seven from MIT receive National Institutes of Health awards

by MIT School of Science |

On Oct. 5, the National Institutes of Health announced the names of 106 scientists who have been awarded grants through the High-Risk, High-Reward Research program to advance highly innovative biomedical and behavioral research. Seven of the recipients are MIT faculty members.

The High-Risk, High-Reward Research program catalyzes scientific discovery by supporting research proposals that, due to their inherent risk, may struggle in the traditional peer-review process despite their transformative potential. Program applicants are encouraged to pursue trailblazing ideas in any area of research relevant to the NIH’s mission to advance knowledge and enhance health.

“The science put forward by this cohort is exceptionally novel and creative and is sure to push at the boundaries of what is known,” says NIH Director Francis S. Collins. “These visionary investigators come from a wide breadth of career stages and show that groundbreaking science can happen at any career level given the right opportunity.”

New innovators

Four MIT researchers received New Innovator Awards, which recognize “unusually innovative research from early career investigators.” They are:

  • Pulin Li is a member at the Whitehead Institute for Biomedical Research and an assistant professor in the Department of Biology. Li combines approaches from synthetic biology, developmental biology, biophysics and systems biology to quantitatively understand the genetic circuits underlying cell-cell communication that creates multicellular behaviors.
  • Seychelle Vos, the Robert A. Swanson (1969) Career Development Professor of Life Sciences in the Department of Biology, studies the interplay of gene expression and genome organization. Her work focuses on understanding how large molecular machineries involved in genome organization and gene transcription regulate each others’ function to ultimately determine cell fate and identity.
  • Xiao Wang, the Thomas D. and Virginia Cabot Assistant Professor of Chemistry and a member of the Broad Institute of MIT and Harvard, aims to develop high-resolution and highly-multiplexed molecular imaging methods across multiple scales toward understanding the physical and chemical basis of brain wiring and function.
  • Alison Wendlandt is a Cecil and Ida Green Career Development Assistant Professor of Chemistry. Wendlandt focuses on the development of selective, catalytic reactions using the tools of organic and organometallic synthesis and physical organic chemistry. Mechanistic study plays a central role in the development of these new transformations.

Transformative researchers

Two MIT researchers have received Transformative Research Awards, which “promote cross-cutting, interdisciplinary approaches that could potentially create or challenge existing paradigms.” The recipients are:

  • Manolis Kellis is a professor of computer science at MIT in the area of computational biology, an associate member of the Broad Institute, and a principal investigator with MIT’s Computer Science and Artificial Intelligence Laboratory. He aims to further our understanding of the human genome by computational integration of large-scale functional and comparative genomics datasets.
  • Myriam Heiman is the Latham Family Career Development Associate Professor of Neuroscience in the Department of Brain and Cognitive Sciences and an investigator in the Picower Institute for Learning and Memory. Heiman studies the selective vulnerability and pathophysiology seen in two neurodegenerative diseases of the basal ganglia, Huntington’s disease, and Parkinson’s disease.

Together, Heiman, Kellis and colleagues will launch a five-year investigation to pinpoint what may be going wrong in specific brain cells and to help identify new treatment approaches for amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with motor neuron disease (FTLD/MND). The project will bring together four labs, including Heiman and Kellis’ labs at MIT, to apply innovative techniques ranging from computational, genomic, and epigenomic analyses of cells from a rich sample of central nervous system tissue, to precision genetic engineering of stem cells and animal models.

Pioneering researchers

  • Polina Anikeeva received a Pioneer Award, which “challenges investigators at all career levels to pursue new research directions and develop groundbreaking, high-impact approaches to a broad area of biomedical, behavioral, or social science.” Anikeeva is an MIT professor of materials science and engineering, a professor of brain and cognitive sciences, and a McGovern Institute for Brain Research associate investigator. She has established a research program that uniquely combines materials synthesis, device fabrication, neurophysiology, and animal models of behavior. Her group carries out projects that understand, invent, and design materials from the level of atoms to functional devices with applications in fundamental neuroscience.

The program is supported by the NIH Common Fund, which oversees programs that pursue major opportunities and gaps throughout the research enterprise that are of great importance to NIH and require collaboration across the agency to succeed. It issues four awards each year: the Pioneer Award, the New Innovator Award, the Transformative Research Award, and the Early Independence Award.

This year, NIH issued 10 Pioneer awards, 64 New Innovator awards, 19 Transformative Research awards (10 general, four ALS-related, and five Covid-19-related), and 13 Early Independence awards for 2021. Funding for the awards comes from the NIH Common Fund, the National Institute of General Medical Sciences, the National Institute of Mental Health, and the National Institute of Neurological Disorders and Stroke.

School of Science welcomes new faculty

Anne Trafton |

This fall, MIT welcomes new faculty members — six assistant professors and two tenured professors — to the departments of Biology; Brain and Cognitive Sciences; Chemistry; Earth, Atmospheric and Planetary Sciences; and Physics.

A physicist, Soonwon Choi is interested in dynamical phenomena that occur in strongly interacting quantum many-body systems far from equilibrium and designing their applications for quantum information science. He takes a variety of interdisciplinary approaches from analytic theory and numerical computations to collaborations on experiments with controlled quantum degrees of freedom. Recently, Choi’s research has encompassed studying the phenomenon of a phase transition in the dynamics of quantum entanglement and information, drawing on machine learning to introduce a quantum convolutional neural network that can recognize quantum states associated with a one-dimensional symmetry-protected topological phase, and exploring a range of quantum applications of the nitrogen-vacancy color center of diamond.

After completing his undergraduate study in physics at Caltech in 2012, Choi received his PhD degree in physics from Harvard University in 2018. He then worked as a Miller Postdoctoral Fellow at the University of California at Berkeley before joining the Department of Physics and the Center for Theoretical Physics as an assistant professor in July 2021.

Olivia Corradin investigates how genetic variants contribute to disease. She focuses on non-coding DNA variants — changes in DNA sequence that can alter the regulation of gene expression — to gain insight into pathogenesis. With her novel outside-variant approach, Corradin’s lab singled out a type of brain cell involved in multiple sclerosis, increasing total heritability identified by three- to five-fold. A recipient of the Avenir Award through the NIH Director’s Pioneer Award Program, Corradin also scrutinizes how genetic and epigenetic variation influence susceptibility to substance abuse disorders. These critical insights into multiple sclerosis, opioid use disorder, and other diseases have the potential to improve risk assessment, diagnosis, treatment, and preventative care for patients.

Corradin completed a bachelor’s degree in biochemistry from Marquette University in 2010 and a PhD in genetics from Case Western Reserve University in 2016. A Whitehead Institute Fellow since 2016, she also became an institute member in July 2021. The Department of Biology welcomes Corradin as an assistant professor.

Arlene Fiore seeks to understand processes that control two-way interactions between air pollutants and the climate system, as well as the sensitivity of atmospheric chemistry to different chemical, physical, and biological sources and sinks at scales ranging from urban to global and daily to decadal. Combining chemistry-climate models and observations from ground, airborne, and satellite platforms, Fiore has identified global dimensions to ground-level ozone smog and particulate haze that arise from linkages with the climate system, global atmospheric composition, and the terrestrial biosphere. She also investigates regional meteorology and climate feedbacks due to aerosols versus greenhouse gases, future air pollution responses to climate change, and drivers of atmospheric oxidizing capacity. A new research direction involves using chemistry-climate model ensemble simulations to identify imprints of climate variability on observational records of trace gases in the troposphere.

After earning a bachelor’s degree and PhD from Harvard University, Fiore held a research scientist position at the Geophysical Fluid Dynamics Laboratory and was appointed as an associate professor with tenure at Columbia University in 2011. Over the last decade, she has worked with air and health management partners to develop applications of satellite and other Earth science datasets to address their emerging needs. Fiore’s honors include the American Geophysical Union (AGU) James R. Holton Junior Scientist Award, Presidential Early Career Award for Scientists and Engineers (the highest honor bestowed by the United States government on outstanding scientists and engineers in the early stages of their independent research careers), and AGU’s James B. Macelwane Medal. The Department of Earth, Atmospheric and Planetary Sciences welcomes Fiore as the first Peter H. Stone and Paola Malanotte Stone Professor.

With a background in magnetism, Danna Freedman leverages inorganic chemistry to solve problems in physics. Within this paradigm, she is creating the next generation of materials for quantum information by designing spin-based quantum bits, or qubits, based in molecules. These molecular qubits can be precisely controlled, opening the door for advances in quantum computation, sensing, and more. She also harnesses high pressure to synthesize new emergent materials, exploring the possibilities of intermetallic compounds and solid-state bonding. Among other innovations, Freedman has realized millisecond coherence times in molecular qubits, created a molecular analogue of an NV center featuring optical read-out of spin, and discovered the first iron-bismuth binary compound.

Freedman received her bachelor’s degree from Harvard University and her PhD from the University of California at Berkeley, then conducted postdoctoral research at MIT before joining the faculty at Northwestern University as an assistant professor in 2012, earning an NSF CAREER Award, the Presidential Early Career Award for Scientists and Engineers, the ACS Award in Pure Chemistry, and more. She was promoted to associate professor in 2018 and full professor with tenure in 2020. Freedman returns to MIT as the Frederick George Keyes Professor of Chemistry.

Kristin Knouse PhD ’17 aims to understand how tissues sense and respond to damage, with the goal of developing new approaches for regenerative medicine. She focuses on the mammalian liver — which has the unique ability to completely regenerate itself — to ask how organisms react to organ injury, how certain cells retain the ability to grow and divide while others do not, and what genes regulate this process. Knouse creates innovative tools, such as a genome-wide CRISPR screening within a living mouse, to examine liver regeneration from the level of a single-cell to the whole organism.

Knouse received a bachelor’s degree in biology from Duke University in 2010 and then enrolled in the Harvard and MIT MD-PhD Program, where she earned a PhD through the MIT Department of Biology in 2016 and an MD through the Harvard-MIT Program in Health Sciences and Technology in 2018. In 2018, she established her independent laboratory at the Whitehead Institute for Biomedical Research and was honored with the NIH Director’s Early Independence Award. Knouse joins the Department of Biology and the Koch Institute for Integrative Cancer Research as an assistant professor.

Lina Necib PhD ’17 is an astroparticle physicist exploring the origin of dark matter through a combination of simulations and observational data that correlate the dynamics of dark matter with that of the stars in the Milky Way. She has investigated the local dynamic structures in the solar neighborhood using the Gaia satellite, contributed to building a catalog of local accreted stars using machine learning techniques, and discovered a new stream called Nyx, after the Greek goddess of the night. Necib is interested in employing Gaia in conjunction with other spectroscopic surveys to understand the dark matter profile in the local solar neighborhood, the center of the galaxy, and in dwarf galaxies.

After obtaining a bachelor’s degree in mathematics and physics from Boston University in 2012 and a PhD in theoretical physics from MIT in 2017, Necib was a Sherman Fairchild Fellow at Caltech, a Presidential Fellow at the University of California at Irvine, and a fellow in theoretical astrophysics at Carnegie Observatories. She returns to MIT as an assistant professor in the Department of Physics and a member of the MIT Kavli Institute for Astrophysics and Space Research.

Andrew Vanderburg studies exoplanets, or planets that orbit stars other than the sun. Conducting astronomical observations from Earth as well as space, he develops cutting-edge methods to learn about planets outside of our solar system. Recently, he has leveraged machine learning to optimize searches and identify planets that were missed by previous techniques. With collaborators, he discovered the eighth planet in the Kepler-90 solar system, a Jupiter-like planet with unexpectedly close orbiting planets, and rocky bodies disintegrating near a white dwarf, providing confirmation of a theory that such stars may accumulate debris from their planetary systems.

Vanderburg received a bachelor’s degree in physics and astrophysics from the University of California at Berkeley in 2013 and a PhD in Astronomy from Harvard University in 2017. Afterward, Vanderburg moved to the University of Texas at Austin as a NASA Sagan Postdoctoral Fellow, then to the University of Wisconsin at Madison as a faculty member. He joins MIT as an assistant professor in the Department of Physics and a member of the Kavli Institute for Astrophysics and Space Research.

A computational neuroscientist, Guangyu Robert Yang is interested in connecting artificial neural networks to the actual functions of cognition. His research incorporates computational and biological systems and uses computational modeling to understand the optimization of neural systems which function to accomplish multiple tasks. As a postdoc, Yang applied principles of machine learning to study the evolution and organization of the olfactory system. The neural networks his models generated show important similarities to the biological circuitry, suggesting that the structure of the olfactory system evolved in order to optimally enable the specific tasks needed for odor recognition.

Yang received a bachelor’s degree in physics from Peking University before obtaining a PhD in computational neuroscience at New York University, followed by an internship in software engineering at Google Brain. Before coming to MIT, he conducted postdoctoral research at the Center for Theoretical Neuroscience of Columbia University, where he was a junior fellow at the Simons Society of Fellows. Yang is an assistant professor in the Department of Brain and Cognitive Sciences with a shared appointment in the Department of Electrical Engineering and Computer Science in the School of Engineering and the MIT Schwarzman College of Computing as well as an associate investigator with the McGovern Institute.

Jacqueline Lees and Rebecca Saxe named associate deans of science

by Julia C. Keller | School of Science |

Jaqueline Lees and Rebecca Saxe have been named associate deans serving in the MIT School of Science. Lees is the Virginia and D.K. Ludwig Professor for Cancer Research and is currently the associate director of the Koch Institute for Integrative Cancer Research, as well as an associate department head and professor in the Department of Biology at MIT. Saxe is the John W. Jarve (1978) Professor in Brain and Cognitive Sciences and the associate head of the Department of Brain and Cognitive Sciences (BCS); she is also an associate investigator in the McGovern Institute for Brain Research.

Lees and Saxe will both contribute to the school’s diversity, equity, inclusion, and justice (DEIJ) activities, as well as develop and implement mentoring and other career-development programs to support the community. From their home departments, Saxe and Lees bring years of DEIJ and mentorship experience to bear on the expansion of school-level initiatives.

Lees currently serves on the dean’s science council in her capacity as associate director of the Koch Institute. In this new role as associate dean for the School of Science, she will bring her broad administrative and programmatic experiences to bear on the next phase for DEIJ and mentoring activities.

Lees joined MIT in 1994 as a faculty member in MIT’s Koch Institute (then the Center for Cancer Research) and Department of Biology. Her research focuses on regulators that control cellular proliferation, terminal differentiation, and stemness — functions that are frequently deregulated in tumor cells. She dissects the role of these proteins in normal cell biology and development, and establish how their deregulation contributes to tumor development and metastasis.

Since 2000, she has served on the Department of Biology’s graduate program committee, and played a major role in expanding the diversity of the graduate student population. Lees also serves on DEIJ committees in her home department, as well as at the Koch Institute.

With co-chair with Boleslaw Wyslouch, director of the Laboratory for Nuclear Science, Lees led the ReseArch Scientist CAreer LadderS (RASCALS) committee tasked to evaluate career trajectories for research staff in the School of Science and make recommendations to recruit and retain talented staff, rewarding them for their contributions to the school’s research enterprise.

“Jackie is a powerhouse in translational research, demonstrating how fundamental work at the lab bench is critical for making progress at the patient bedside,” says Nergis Mavalvala, dean of the School of Science. “With Jackie’s dedicated and thoughtful partnership, we can continue to lead in basic research and develop the recruitment, retention, and mentoring and necessary to support our community.”

Saxe will join Lees in supporting and developing programming across the school that could also provide direction more broadly at the Institute.

“Rebecca is an outstanding researcher in social cognition and a dedicated educator — someone who wants our students not only to learn, but to thrive,” says Mavalvala. “I am grateful that Rebecca will join the dean’s leadership team and bring her mentorship and leadership skills to enhance the school.”

For example, in collaboration with former department head James DiCarlo, the BCS department has focused on faculty mentorship of graduate students; and, in collaboration with Professor Mark Bear, the department developed postdoc salary and benefit standards. Both initiatives have become models at MIT.

With colleague Laura Schulz, Saxe also served as co-chair of the Committee on Medical Leave and Hospitalizations (CMLH), which outlined ways to enhance MIT’s current leave and hospitalization procedures and policies for undergraduate and graduate students. Saxe was also awarded MIT’s Committed to Caring award for excellence in graduate student mentorship, as well as the School of Science’s award for excellence in undergraduate teaching.

In her research, Saxe studies human social cognition, using a combination of behavioral testing and brain imaging technologies. She is best known for her work on brain regions specialized for abstract concepts, such as “theory of mind” tasks that involve understanding the mental states of other people. Her TED Talk, “How we read each other’s minds” has been viewed more than 3 million times. She also studies the development of the human brain during early infancy.

She obtained her PhD from MIT and was a Harvard University junior fellow before joining the MIT faculty in 2006. In 2014, the National Academy of Sciences named her one of two recipients of the Troland Award for investigators age 40 or younger “to recognize unusual achievement and further empirical research in psychology regarding the relationships of consciousness and the physical world.” In 2020, Saxe was named a John Simon Guggenheim Foundation Fellow.

Saxe and Lees will also work closely with Kuheli Dutt, newly hired assistant dean for diversity, equity, and inclusion, and other members of the dean’s science council on school-level initiatives and strategy.

“I’m so grateful that Rebecca and Jackie have agreed to take on these new roles,” Mavalvala says. “And I’m super excited to work with these outstanding thought partners as we tackle the many puzzles that I come across as dean.”

Mehrdad Jazayeri wants to know how our brains model the external world

Anne Trafton |

Much of our daily life requires us to make inferences about the world around us. As you think about which direction your tennis opponent will hit the ball, or try to figure out why your child is crying, your brain is searching for answers about possibilities that are not directly accessible through sensory experiences.

MIT Associate Professor Mehrdad Jazayeri has devoted most of his career to exploring how the brain creates internal representations, or models, of the external world to make intelligent inferences about hidden states of the world.

“The one question I am most interested in is how does the brain form internal models of the external world? Studying inference is really a powerful way of gaining insight into these internal models,” says Jazayeri, who recently earned tenure in the Department of Brain and Cognitive Sciences and is also a member of MIT’s McGovern Institute for Brain Research.

Using a variety of approaches, including detailed analysis of behavior, direct recording of activity of neurons in the brain, and mathematical modeling, he has discovered how the brain builds models of statistical regularities in the environment. He has also found circuits and mechanisms that enable the brain to capture the causal relationships between observations and outcomes.

An unusual path

Jazayeri, who has been on the faculty at MIT since 2013, took an unusual path to a career in neuroscience. Growing up in Tehran, Iran, he was an indifferent student until his second year of high school when he got interested in solving challenging geometry puzzles. He also started programming with the ZX Spectrum, an early 8-bit personal computer, that his father had given him.

During high school, he was chosen to train for Iran’s first ever National Physics Olympiad team, but when he failed to make it to the international team, he became discouraged and temporarily gave up on the idea of going to college. Eventually, he participated in the University National Entrance Exam and was admitted to the electrical engineering department at Sharif University of Technology.

Jazayeri didn’t enjoy his four years of college education. The experience mostly helped him realize that he was not meant to become an engineer. “I realized that I’m not an inventor. What inspires me is the process of discovery,” he says. “I really like to figure things out, not build things, so those four years were not very inspiring.”

After graduating from college, Jazayeri spent a few years working on a banana farm near the Caspian Sea, along with two friends. He describes those years as among the best and most formative of his life. He would wake by 4 a.m., work on the farm until late afternoon, and spend the rest of the day thinking and reading. One topic he read about with great interest was neuroscience, which led him a few years later to apply to graduate school.

He immigrated to Canada and was admitted to the University of Toronto, where he earned a master’s degree in physiology and neuroscience. While there, he worked on building small circuit models that would mimic the activity of neurons in the hippocampus.

From there, Jazayeri went on to New York University to earn a PhD in neuroscience, where he studied how signals in the visual cortex support perception and decision-making. “I was less interested in how the visual cortex encodes the external world,” he says. “I wanted to understand how the rest of the brain decodes the signals in visual cortex, which is, in effect, an inference problem.”

He continued pursuing his interest in the neurobiology of inference as a postdoc at the University of Washington, where he investigated how the brain uses temporal regularities in the environment to estimate time intervals, and uses knowledge about those intervals to plan for future actions.

Building internal models to make inferences

Inference is the process of drawing conclusions based on information that is not readily available. Making rich inferences from scarce data is one of humans’ core mental capacities, one that is central to what makes us the most intelligent species on Earth. To do so, our nervous system builds internal models of the external world, and those models that help us think through possibilities without directly experiencing them.

The problem of inferences presents itself in many behavioral settings.

“Our nervous system makes all sorts of internal models for different behavioral goals, some that capture the statistical regularities in the environment, some that link potential causes to effects, some that reflect relationships between entities, and some that enable us to think about others,” Jazayeri says.

Jazayeri’s lab at MIT is made up of a group of cognitive scientists, electrophysiologists, engineers, and physicists with a shared interest in understanding the nature of internal models in the brain and how those models enable us to make inferences in different behavioral tasks.

Early work in the lab focused on a simple timing task to examine the problem of statistical inference, that is, how we use statistical regularities in the environment to make accurate inference. First, they found that the brain coordinates movements in time using a dynamic process, akin to an analog timer. They also found that the neural representation of time in the frontal cortex is being continuously calibrated based on prior experience so that we can make more accurate time estimates in the presence of uncertainty.

Later, the lab developed a complex decision-making task to examine the neural basis of causal inference, or the process of deducing a hidden cause based on its effects. In a paper that appeared in 2019, Jazayeri and his colleagues identified a hierarchical and distributed brain circuit in the frontal cortex that helps the brain to determine the most probable cause of failure within a hierarchy of decisions.

More recently, the lab has extended its investigation to other behavioral domains, including relational inference and social inference. Relational inference is about situating an ambiguous observation using relational memory. For example, coming out of a subway in a new neighborhood, we may use our knowledge of the relationship between visible landmarks to infer which way is north. Social inference, which is extremely difficult to study, involves deducing other people’s beliefs and goals based on their actions.

Along with studies in human volunteers and animal models, Jazayeri’s lab develops computational models based on neural networks, which helps them to test different possible hypotheses of how the brain performs specific tasks. By comparing the activity of those models with neural activity data from animals, the researchers can gain insight into how the brain actually performs a particular type of inference task.

“My main interest is in how the brain makes inferences about the world based on the neural signals,” Jazayeri says. “All of my work is about looking inside the brain, measuring signals, and using mathematical tools to try to understand how those signals are manifestations of an internal model within the brain.”

Some brain disorders exhibit similar circuit malfunctions

Anne Trafton |

Many neurodevelopmental disorders share similar symptoms, such as learning disabilities or attention deficits. A new study from MIT has uncovered a common neural mechanism for a type of cognitive impairment seen in some people with autism and schizophrenia, even though the genetic variations that produce the impairments are different for each condition.

In a study of mice, the researchers found that certain genes that are mutated or missing in some people with those disorders cause similar dysfunctions in a neural circuit in the thalamus. If scientists could develop drugs that target this circuit, they could be used to treat people who have different disorders with common behavioral symptoms, the researchers say.

“This study reveals a new circuit mechanism for cognitive impairment and points to a future direction for developing new therapeutics, by dividing patients into specific groups not by their behavioral profile, but by the underlying neurobiological mechanisms,” 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, the associate director of the McGovern Institute for Brain Research at MIT, and the senior author of the new study.

Dheeraj Roy, a Warren Alpert Distinguished Scholar and a McGovern Fellow at the Broad Institute, and Ying Zhang, a postdoc at the McGovern Institute, are the lead authors of the paper, which appears today in Neuron.

Thalamic connections

The thalamus plays a key role in cognitive tasks such as memory formation and learning. Previous studies have shown that many of the gene variants linked to brain disorders such as autism and schizophrenia are highly expressed in the thalamus, suggesting that it may play a role in those disorders.

One such gene is called Ptchd1, which Feng has studied extensively. In boys, loss of this gene, which is carried on the X chromosome, can lead to attention deficits, hyperactivity, aggression, intellectual disability, and autism spectrum disorders.

In a study published in 2016, Feng and his colleagues showed that Ptchd1 exerts many of its effects in a part of the thalamus called the thalamic reticular nucleus (TRN). When the gene is knocked out in the TRN of mice, the mice show attention deficits and hyperactivity. However, that study did not find any role for the TRN in the learning disabilities also seen in people with mutations in Ptchd1.

In the new study, the researchers decided to look elsewhere in the thalamus to try to figure out how Ptchd1 loss might affect learning and memory. Another area they identified that highly expresses Ptchd1 is called the anterodorsal (AD) thalamus, a tiny region that is involved in spatial learning and communicates closely with the hippocampus.

Using novel techniques that allowed them to trace the connections between the AD thalamus and another brain region called the retrosplenial cortex (RSC), the researchers determined a key function of this circuit. They found that in mice, the AD-to-RSC circuit is essential for encoding fearful memories of a chamber in which they received a mild foot shock. It is also necessary for working memory, such as creating mental maps of physical spaces to help in decision-making.

The researchers found that a nearby part of the thalamus called the anteroventral (AV) thalamus also plays a role in this memory formation process: AV-to-RSC communication regulates the specificity of the encoded memory, which helps us distinguish this memory from others of similar nature.

“These experiments showed that two neighboring subdivisions in the thalamus contribute differentially to memory formation, which is not what we expected,” Roy says.

Circuit malfunction

Once the researchers discovered the roles of the AV and AD thalamic regions in memory formation, they began to investigate how this circuit is affected by loss of Ptchd1. When they knocked down expression of Ptchd1 in neurons of the AD thalamus, they found a striking deficit in memory encoding, for both fearful memories and working memory.

The researchers then did the same experiments with a series of four other genes — one that is linked with autism and three linked with schizophrenia. In all of these mice, they found that knocking down gene expression produced the same memory impairments. They also found that each of these knockdowns produced hyperexcitability in neurons of the AD thalamus.

These results are consistent with existing theories that learning occurs through the strengthening of synapses that occurs as a memory is formed, the researchers say.

“The dominant theory in the field is that when an animal is learning, these neurons have to fire more, and that increase correlates with how well you learn,” Zhang says. “Our simple idea was if a neuron fires too high at baseline, you may lack a learning-induced increase.”

The researchers demonstrated that each of the genes they studied affects different ion channels that influence neurons’ firing rates. The overall effect of each mutation is an increase in neuron excitability, which leads to the same circuit-level dysfunction and behavioral symptoms.

The researchers also showed that they could restore normal cognitive function in mice with these genetic mutations by artificially turning down hyperactivity in neurons of the AD thalamus. The approach they used, chemogenetics, is not yet approved for use in humans. However, it may be possible to target this circuit in other ways, the researchers say.

The findings lend support to the idea that grouping diseases by the circuit malfunctions that underlie them may help to identify potential drug targets that could help many patients, Feng says.

“There are so many genetic factors and environmental factors that can contribute to a particular disease, but in the end, it has to cause some type of neuronal change that affects a circuit or a few circuits involved in this behavior,” he says. “From a therapeutic point of view, in such cases you may not want to go after individual molecules because they may be unique to a very small percentage of patients, but at a higher level, at the cellular or circuit level, patients may have more commonalities.”

The research was funded by the Stanley Center at the Broad Institute, the Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, the James and Patricia Poitras Center for Psychiatric Disorders Research at MIT, and the National Institutes of Health BRAIN Initiative.

Queen of hearts

Anne Trafton |

Amphibians and humans differ in many ways, but Laurie Boyer, a professor of biology and biological engineering at MIT, is particularly interested in one of those differences. Certain types of amphibians and fish can regenerate and heal their hearts after an injury. In contrast, human adults who have experienced trauma to the heart, such as in the case of a heart attack or exposure to certain medications, are unable to repair the damage. Often, the injured heart ends up with scar tissue that can lead to heart failure.

Recent research in this area now indicates that mice, and even humans, have some capacity for cardiac repair for a short period after birth. But after even just a few days of age, that ability starts to shut off. “The heart has very limited ability to repair itself in response to injury, disease, or aging,” Boyer says.

Alexander Auld, a postdoc in the Boyer Lab, studies the key cellular mechanisms that lead heart cells to mature and lose regenerative potential. Specifically, he’s interested in understanding how cardiomyocytes, the heart cells responsible for pumping blood, develop an ability to contract and relax repeatedly. Auld tests the function of proteins that serve as signals to assemble the cardiac muscle structure after birth. The assembly of these structures coincides with the loss of regenerative ability.

“I’m trying to piece together: What are the different mechanisms that push cardiomyocytes to assemble their contractile apparatus and to stop dividing?” Auld says. “Solving this puzzle may have potential to stimulate regeneration in the adult heart muscle.”

“The holy grail of regenerative biology would be to stimulate your own heart cells to replenish themselves,” says Boyer, who joined the MIT faculty in 2007. “Before this approach is possible, we need to achieve a deep understanding of the fundamental processes that drive heart development.”

Boyer’s lab studies how many different signals and genes interact to affect heart development. The work will enable a better understanding of how faulty regulation can lead to disease, and may also enable new therapies for people suffering from a variety of heart conditions.

Critical connections

Recently, Boyer’s lab has been studying heart development in people with Trisomy 21, or Down syndrome. Every year, 6,000 babies born in the United States have Down syndrome. Around half have heart defects. The most common heart defect in babies with Down syndrome is a hole in the heart’s center, called an atrioventricular septal defect. It is often repaired with surgery, but the repair can cause scar tissue and cardiovascular complications.

Somatic cells are those that compose an organism’s body; they differ from sex cells, which are used for reproduction. Most people have 46 chromosomes, arranged in 23 pairs, in their body’s somatic cells. In 95 percent of cases, Down syndrome results when a person has three copies of chromosome 21 instead of two –– a total of 47 chromosomes per cell. It’s an example of aneuploidy, when a cell has an abnormal number of chromosomes. Cellular attempts to adapt to the extra chromosome can cause stress on the body’s cells, including those of the heart.

MIT’s Alana Down Syndrome Center (ADSC) brings together biologists, neuroscientists, engineers, and other experts to increase knowledge about Down syndrome. ADSC launched in early 2019, led by Angelika Amon, professor of biology and a member of the Koch Institute for Integrative Cancer Research, along with co-director Li-Huei Tsai, Picower Professor and director of the Picower Institute for Learning and Memory. Amon died at age 53 in 2020 after a battle with ovarian cancer. At MIT, Amon had studied the effects of aneuploidy on cells.

“In my many wonderful scientific and personal discussions with Angelika, who was a beacon of inspiration to me, it became clear that studying Trisomy 21 in the context of heart development could ultimately improve the lives of these individuals,” Boyer says.

Change of heart

To conduct their research, Boyer’s group uses human induced pluripotent cells (hiPSCs), obtained through somatic cell reprogramming. The revolutionary technique was developed by Sir John B. Gurdon and Shinya Yamanaka, who in 2012 won the Nobel Prize in Physiology or Medicine for their work. Reprogramming works by converting specialized, mature somatic cells with one particular function into specialized, mature, cells with a different function.

Boyer’s lab uses hiPSCs from human adults with Down syndrome and converts them into cardiomyocytes through somatic cell reprogramming. Then, they compare those cardiomyocytes with reprogrammed cells from individuals who do not have Down syndrome. This work helps them deduce why the extra chromosome in people with Down syndrome may cause congenital heart defects.

“We can now begin to pinpoint the faulty signals and genes in Trisomy 21 cardiac cells that affect heart development,” Boyer says. “And with that same idea, we can also discover how we might actually be able to ameliorate or fix these defects.”

With this technique, the team can track how aspects of a specific patient’s cell development correlate with their clinical presentation. The ability to analyze patient-specific cells also has implications for personalized medicine, Boyer says. For instance, a patient’s skin or blood cells –– which are more easily obtained –– could be converted into a highly specialized mature cell, like a cardiac muscle cell, and tested for its response to drugs that could possibly cause damage to the heart before they reach the clinic. This process can also be used to screen for new therapies that can improve the outcome for heart failure patients.

Boyer presented the group’s research on Down syndrome at the New England Down Syndrome Symposium, co-organized in November 2020 by MIT, ADSC, Massachusetts Down Syndrome Congress, and LuMind IDSC Foundation.

Heart of the operation

Boyer’s lab employs students at the undergraduate, graduate, and postdoc levels from engineering, life sciences, and computer sciences –– each of whom, Boyer says, brings unique expertise and value to the team.

“It’s important for me to have a lab where everyone feels welcome, and that they feel that they can contribute to these fundamental discoveries,” Boyer says.

The Boyer Lab often works with scholars across disciplines at MIT. “It’s really great,” Auld says. “You can investigate a problem using multiple tools and perspectives.”

One project, in partnership with George Barbastathis, a professor in mechanical engineering, uses image-based machine learning to understand structural differences within cardiomyocytes when the proteins that signal cells to develop have been manipulated. Auld generates high-resolution images that the machine learning algorithms can analyze.

Another project, in collaboration with Ed Boyden, a professor in the Department of Biological Engineering as well as the McGovern Institute for Brain Research, involves the development of new technologies that allow high-throughput imaging of cardiac cells. The cross-pollination across departments and areas of expertise at MIT, Boyer says, often has her feeling like “a kid in a candy shop.”

“That our work could ultimately impact human health is very fulfilling for me, and the ability to use our scientific discoveries to improve medical outcomes is an important direction of my lab,” Boyer says. “Given the enormous talent at MIT and the excitement and willingness of everyone here to work together, we have an unprecedented opportunity to solve important problems that can make a difference in people’s lives.”

Biologists discover a trigger for cell extrusion

Anne Trafton |

For all animals, eliminating some cells is a necessary part of embryonic development. Living cells are also naturally sloughed off in mature tissues; for example, the lining of the intestine turns over every few days.

One way that organisms get rid of unneeded cells is through a process called extrusion, which allows cells to be squeezed out of a layer of tissue without disrupting the layer of cells left behind. MIT biologists have now discovered that this process is triggered when cells are unable to replicate their DNA during cell division.

The researchers discovered this mechanism in the worm C. elegans, and they showed that the same process can be driven by mammalian cells; they believe extrusion may serve as a way for the body to eliminate cancerous or precancerous cells.

“Cell extrusion is a mechanism of cell elimination used by organisms as diverse as sponges, insects, and humans,” says H. Robert Horvitz, the David H. Koch Professor of Biology at MIT, a member of the McGovern Institute for Brain Research and the Koch Institute for Integrative Cancer Research, a Howard Hughes Medical Institute investigator, and the senior author of the study. “The discovery that extrusion is driven by a failure in DNA replication was unexpected and offers a new way to think about and possibly intervene in certain diseases, particularly cancer.”

MIT postdoc Vivek Dwivedi is the lead author of the paper, which appears today in Nature. Other authors of the paper are King’s College London research fellow Carlos Pardo-Pastor, MIT research specialist Rita Droste, MIT postdoc Ji Na Kong, MIT graduate student Nolan Tucker, Novartis scientist and former MIT postdoc Daniel Denning, and King’s College London professor of biology Jody Rosenblatt.

Stuck in the cell cycle

In the 1980s, Horvitz was one of the first scientists to analyze a type of programmed cell suicide called apoptosis, which organisms use to eliminate cells that are no longer needed. He made his discoveries using C. elegans, a tiny nematode that contains exactly 959 cells. The developmental lineage of each cell is known, and embryonic development follows the same pattern every time. Throughout this developmental process, 1,090 cells are generated, and 131 cells undergo programmed cell suicide by apoptosis.

Horvitz’s lab later showed that if the worms were genetically mutated so that they could not eliminate cells by apoptosis, a few of those 131 cells would instead be eliminated by cell extrusion, which appears to be able to serve as a backup mechanism to apoptosis. How this extrusion process gets triggered, however, remained a mystery.

To unravel this mystery, Dwivedi performed a large-scale screen of more than 11,000 C. elegans genes. One by one, he and his colleagues knocked down the expression of each gene in worms that could not perform apoptosis. This screen allowed them to identify genes that are critical for turning on cell extrusion during development.

To the researchers’ surprise, many of the genes that turned up as necessary for extrusion were involved in the cell division cycle. These genes were primarily active during first steps of the cell cycle, which involve initiating the cell division cycle and copying the cell’s DNA.

Further experiments revealed that cells that are eventually extruded do initially enter the cell cycle and begin to replicate their DNA. However, they appear to get stuck in this phase, leading them to be extruded.

Most of the cells that end up getting extruded are unusually small, and are produced from an unequal cell division that results in one large daughter cell and one much smaller one. The researchers showed that if they interfered with the genes that control this process, so that the two daughter cells were closer to the same size, the cells that normally would have been extruded were able to successfully complete the cell cycle and were not extruded.

The researchers also showed that the failure of the very small cells to complete the cell cycle stems from a shortage of the proteins and DNA building blocks needed to copy DNA. Among other key proteins, the cells likely don’t have enough of an enzyme called LRR-1, which is critical for DNA replication. When DNA replication stalls, proteins that are responsible for detecting replication stress quickly halt cell division by inactivating a protein called CDK1. CDK1 also controls cell adhesion, so the researchers hypothesize that when CDK1 is turned off, cells lose their stickiness and detach, leading to extrusion.

Cancer protection

Horvitz’s lab then teamed up with researchers at King’s College London, led by Rosenblatt, to investigate whether the same mechanism might be used by mammalian cells. In mammals, cell extrusion plays an important role in replacing the lining of the intestines, lungs, and other organs.

The researchers used a chemical called hydroxyurea to induce DNA replication stress in canine kidney cells grown in cell culture. The treatment quadrupled the rate of extrusion, and the researchers found that the extruded cells made it into the phase of the cell cycle where DNA is replicated before being extruded. They also showed that in mammalian cells, the well-known cancer suppressor p53 is involved in initiating extrusion of cells experiencing replication stress.

That suggests that in addition to its other cancer-protective roles, p53 may help to eliminate cancerous or precancerous cells by forcing them to extrude, Dwivedi says.

“Replication stress is one of the characteristic features of cells that are precancerous or cancerous. And what this finding suggests is that the extrusion of cells that are experiencing replication stress is potentially a tumor suppressor mechanism,” he says.

The fact that cell extrusion is seen in so many animals, from sponges to mammals, led the researchers to hypothesize that it may have evolved as a very early form of cell elimination that was later supplanted by programmed cell suicide involving apoptosis.

“This cell elimination mechanism depends only on the cell cycle,” Dwivedi says. “It doesn’t require any specialized machinery like that needed for apoptosis to eliminate these cells, so what we’ve proposed is that this could be a primordial form of cell elimination. This means it may have been one of the first ways of cell elimination to come into existence, because it depends on the same process that an organism uses to generate many more cells.”

Dwivedi, who earned his PhD at MIT, was a Khorana scholar before entering MIT for graduate school. This research was supported by the Howard Hughes Medical Institute and the National Institutes of Health.

Josh McDermott seeks to replicate the human auditory system

Anne Trafton |

The human auditory system is a marvel of biology. It can follow a conversation in a noisy restaurant, learn to recognize words from languages we’ve never heard before, and identify a familiar colleague by their footsteps as they walk by our office.

So far, even the most sophisticated computational models cannot perform such tasks as well as the human auditory system, but MIT neuroscientist Josh McDermott hopes to change that. Achieving this goal would be a major step toward developing new ways to help people with hearing loss, says McDermott, who recently earned tenure in MIT’s Department of Brain and Cognitive Sciences.

“Our long-term goal is to build good predictive models of the auditory system,” McDermott says.

“If we were successful in that goal, then it would really transform our ability to make people hear better, because we could design a computer program to figure out what to do to incoming sound to make it easier to recognize what somebody said or where a sound is coming from.”

McDermott’s lab also explores how exposure to different types of music affects people’s music preferences and even how they perceive music. Such studies can help to reveal elements of sound perception that are “hardwired” into our brains, and other elements that are influenced by exposure to different kinds of sounds.

“We have found that there is cross-cultural variation in things that people had widely supposed were universal and possibly even innate,” McDermott says.

Sound perception

As an undergraduate at Harvard University, McDermott originally planned to study math and physics, but “I was very quickly seduced by the brain,” he says. At the time, Harvard did not offer a major in neuroscience, so McDermott created his own, with a focus on vision.

After earning a master’s degree from University College London, he came to MIT to do a PhD in brain and cognitive sciences. His focus was still on vision, which he studied with Ted Adelson, the John and Dorothy Wilson Professor of Vision Science, but he found himself increasingly interested in audition. He had always loved music, and around this time, he started working as a radio and club DJ. “I was spending a lot of time thinking about sound and why things sound the way they do,” he recalls.

To pursue his new interest, he served as a postdoc at the University of Minnesota, where he worked in a lab devoted to psychoacoustics — the study of how humans perceive sound. There, he studied auditory phenomena such as the “cocktail party effect,” or the ability to focus on a particular person’s voice while tuning out background noise. During another postdoc at New York University, he started working on computational models of the auditory system. That interest in computation is part of what drew him back to MIT as a faculty member, in 2013.

“The culture here surrounding brain and cognitive science really prioritizes and values computation, and that was a perspective that was important to me,” says McDermott, who is also a member of MIT’s McGovern Institute for Brain Research and the Center for Brains, Minds and Machines. “I knew that was the kind of work I really wanted to do in my lab, so it just felt like a natural environment for doing that work.”

One aspect of audition that McDermott’s lab focuses on is “auditory scene analysis,” which includes tasks such as inferring what events in the environment caused a particular sound, and determining where a particular sound came from. This requires the ability to disentangle sounds produced by different events or objects, and the ability to tease out the effects of the environment. For instance, a basketball bouncing on a hardwood floor in a gym makes a different sound than a basketball bouncing on an outdoor paved court.

“Sounds in the world have very particular properties, due to physics and the way that the world works,” McDermott says. “We believe that the brain internalizes those regularities, and you have models in your head of the way that sound is generated. When you hear something, you are performing an inference in that model to figure out what is likely to have happened that caused the sound.”

A better understanding of how the brain does this may eventually lead to new strategies to enhance human hearing, McDermott says.

“Hearing impairment is the most common sensory disorder. It affects almost everybody as they get older, and the treatments are OK, but they’re not great,” he says. “We’re eventually going to all have personalized hearing aids that we walk around with, and we just need to develop the right algorithms in order to tell them what to do. That’s something we’re actively working on.”

Music in the brain

About 10 years ago, when McDermott was a postdoc, he started working on cross-cultural studies of how the human brain perceives music. Richard Godoy, an anthropologist at Brandeis University, asked McDermott to join him for some studies of the Tsimane’ people, who live in the Amazon rainforest. Since then, McDermott and some of his students have gone to Bolivia most summers to study sound perception among the Tsimane’. The Tsimane’ have had very little exposure to Western music, making them ideal subjects to study how listening to certain kinds of music influences human sound perception.

These studies have revealed both differences and similarities between Westerners and the Tsimane’ people. McDermott, who counts soul, disco, and jazz-funk among his favorite types of music, has found that Westerners and the Tsimane’ differ in their perceptions of dissonance. To Western ears, for example, the chord of C and F# sounds very unpleasant, but not to the Tsimane’.

He has also shown that that people in Western society perceive sounds that are separated by an octave to be similar, but the Tsimane’ do not. However, there are also some similarities between the two groups. For example, the upper limit of frequencies that can be perceived appears to be the same regardless of music exposure.

“We’re finding both striking variation in some perceptual traits that many people presumed were common across cultures and listeners, and striking similarities in others,” McDermott says. “The similarities and differences across cultures dissociate aspects of perception that are tightly coupled in Westerners, helping us to parcellate perceptual systems into their underlying components.”

Investigating the embattled brain

by Laura Carter | School of Science + Julie Pryor | McGovern Institute |

Omar Rutledge served as a US Army infantryman in the 1st Armored and 25th Infantry Divisions. He was deployed in support of Operation Iraqi Freedom from March 2003 to July 2004. Photo: Omar Rutledge

As an Iraq war veteran, Omar Rutledge is deeply familiar with post-traumatic stress – recurring thoughts and memories that persist long after a danger has passed – and he knows that a brain altered by trauma is not easily fixed. But as a graduate student in the Department of Brain and Cognitive Sciences, Rutledge is determined to change that. He wants to understand exactly how trauma alters the brain – and whether the tools of neuroscience can be used to help fellow veterans with post-traumatic stress disorder (PTSD) heal from their experiences.

“In the world of PTSD research, I look to my left and to my right, and I don’t see other veterans, certainly not former infantrymen,” says Rutledge, who served in the US Army and was deployed to Iraq from March 2003 to July 2004. “If there are so few of us in this space, I feel like I have an obligation to make a difference for all who suffer from the traumatic experiences of war.”

Rutledge is uniquely positioned to make such a difference in the lab of McGovern Investigator John Gabrieli, where researchers use technologies like magnetic resonance imaging (MRI), electroencephalography (EEG), and magnetoencephalography (MEG) to peer into the human brain and explore how it powers our thoughts, memories, and emotions. Rutledge is studying how PTSD weakens the connection between the amygdala, which is responsible for emotions like fear, and the prefrontal cortex, which regulates or controls these emotional responses. He hopes these studies will eventually lead to the development of wearable technologies that can retrain the brain to be less responsive to triggering events.

“I feel like it has been a mission of mine to do this kind of work.”

Though Covid-19 has unexpectedly paused some aspects of his research, Rutledge is pursuing another line of research inspired both by the mandatory social distancing protocols imposed during the lockdown and his own experiences with social isolation. Does chronic social isolation cause physical or chemical changes in the brain similar to those seen in PTSD? And does loneliness exacerbate symptoms of PTSD?

“There’s this hypervigilance that occurs in loneliness, and there’s also something very similar that occurs in PTSD — a heightened awareness of potential threats,” says Rutledge, who is the recipient of Michael Ferrara Graduate Fellowship provided by the Poitras Center, a fellowship made possible by the many friends and family of Michael Ferrara. “The combination of the two may lead to more adverse reactions in people with PTSD.”

In the future, Rutledge hopes to explore whether chronic loneliness impairs reasoning and logic skills and has a deeper impact on veterans who have PTSD.

Although his research tends to resurface painful memories of his own combat experiences, Rutledge says if it can help other veterans heal, it’s worth it.  “In the process, it makes me a little bit stronger as well,” he adds.