Author: mantulin

Facundo Batista among MIT affiliates elected to National Academy of Medicine for 2025

Professors Facundo Batista and Dina Katabi, along with three additional MIT alumni, are honored for their outstanding professional achievement and commitment to service.

Lillian Eden | Jane Halpern | Department of Biology | Department of Electrical Engineering and Computer Science
October 22, 2025

On Oct. 20 during its annual meeting, the National Academy of Medicine announced the election of 100 new members, including MIT faculty members Dina Katabi and Facundo Batista, along with three additional MIT alumni.

Election to the National Academy of Medicine (NAM) is considered one of the highest honors in the fields of health and medicine, recognizing individuals who have demonstrated outstanding professional achievement and commitment to service.

Facundo Batista is the associate director and scientific director of the Ragon Institute of MGH, MIT and Harvard, as well as the first Phillip T. and Susan M. Ragon Professor in the MIT Department of Biology. The National Academy of Medicine recognized Batista for “his work unraveling the biology of antibody-producing B cells to better understand how our body’s immune systems responds to infectious disease.” More recently, Facundo’s research has advanced preclinical vaccine and therapeutic development for globally important diseases including HIV, malaria, and influenza.

Batista earned a PhD from the International School of Advanced Studies and established his lab in 2002 as a member of the Francis Crick Institute (formerly the London Research Institute), simultaneously holding a professorship at Imperial College London. In 2016, he joined the Ragon Institute to pursue a new research program applying his expertise in B cells and antibody responses to vaccine development, and preclinical vaccinology for diseases including SARS-CoV-2 and HIV. Batista is an elected fellow or member of the U.K. Academy of Medical Sciences, the American Academy of Microbiology, the Academia de Ciencias de América Latina, and the European Molecular Biology Organization, and he is chief editor of The EMBO Journal.

Dina Katabi SM ’99, PhD ’03 is the Thuan (1990) and Nicole Pham Professor in the Department of Electrical Engineering and Computer Science at MIT. Her research spans digital health, wireless sensing, mobile computing, machine learning, and computer vision. Katabi’s contributions include efficient communication protocols for the internet, advanced contactless biosensors, and novel AI models that interpret physiological signals. The NAM recognized Katabi for “pioneering digital health technology that enables non-invasive, off-body remote health monitoring via AI and wireless signals, and for developing digital biomarkers for Parkinson’s progression and detection. She has translated this technology to advance objective, sensitive measures of disease trajectory and treatment response in clinical trials.”

Katabi is director of the MIT Center for Wireless Networks and Mobile Computing. She is also a member of the Computer Science and Artificial Intelligence Laboratory (CSAIL), where she leads the Networks at MIT Research Group. Katabi received a bachelor’s degree from the University of Damascus and MS and PhD degrees in computer science from MIT. She is a MacArthur Fellow; a member of the American Academy of Arts and Sciences, National Academy of Sciences, and National Academy of Engineering; and a recipient of the ACM Computing Prize.

Additional MIT alumni who were elected to the NAM for 2025 are:

  • Christopher S. Chen SM ’93, PhD ’97, an alumnus of the Department of Mechanical Engineering and the Harvard-MIT Program in Health Sciences and Technology;
  • Michael E. Matheny SM ’06, an alumnus of the Harvard-MIT Program in Health Sciences and Technology; and
  • Rebecca R. Richards-Kortum SM ’87, PhD ’90, and alumna of the Department of Physics and the Harvard-MIT Program in Health Sciences and Technology.

Established originally as the Institute of Medicine in 1970 by the National Academy of Sciences, the National Academy of Medicine addresses critical issues in health, science, medicine, and related policy, and inspires positive actions across sectors.

“I am deeply honored to welcome these extraordinary health and medicine leaders and researchers into the National Academy of Medicine,” says NAM President Victor J. Dzau. “Their demonstrated excellence in tackling public health challenges, leading major discoveries, improving health care, advancing health policy, and addressing health equity will critically strengthen our collective ability to tackle the most pressing health challenges of our time.”

Department of Biology welcomes new faculty Yunha Hwang in shared position with EECS, Schwarzman College of Computing

Hwang is one of 11 new faculty members that occupy core computing and shared positions, bringing varied backgrounds and expertise to the MIT community.

Amanda Diehl | MIT Schwarzman College of Computing
October 17, 2025

The MIT Schwarzman College of Computing welcomes 11 new faculty members in core computing and shared positions to the MIT community. They bring varied backgrounds and expertise spanning sustainable design, satellite remote sensing, decision theory, and the development of new algorithms for declarative artificial intelligence programming, among others.

“I warmly welcome this talented group of new faculty members. Their work lies at the forefront of computing and its broader impact in the world,” says Dan Huttenlocher, dean of the MIT Schwarzman College of Computing and the Henry Ellis Warren Professor of Electrical Engineering and Computer Science.

College faculty include those with appointments in the Department of Electrical Engineering and Computer Science (EECS) or in the Institute for Data, Systems, and Society (IDSS), which report into both the MIT Schwarzman College of Computing and the School of Engineering. There are also several new faculty members in shared positions between the college and other MIT departments and sections, including Political Science, Linguistics and Philosophy, History, and Architecture.

“Thanks to another successful year of collaborative searches, we have hired six additional faculty in shared positions, bringing the total to 20,” says Huttenlocher.

The new shared faculty include:

Bailey Flanigan is an assistant professor in the Department of Political Science, holding an MIT Schwarzman College of Computing shared position with EECS. Her research combines tools from social choice theory, game theory, algorithms, statistics, and survey methods to advance political methodology and strengthen democratic participation. She is interested in sampling algorithms, opinion measurement, and the design of democratic innovations like deliberative minipublics and participatory budgeting. Flanigan was a postdoc at Harvard University’s Data Science Initiative, and she earned her PhD in computer science from Carnegie Mellon University.

Brian Hedden PhD ’12 is a professor in the Department of Linguistics and Philosophy, holding an MIT Schwarzman College of Computing shared position with EECS. His research focuses on how we ought to form beliefs and make decisions. His works span epistemology, decision theory, and ethics, including ethics of AI. He is the author of “Reasons without Persons: Rationality, Identity, and Time” (Oxford University Press, 2015) and articles on topics such as collective action problems, legal standards of proof, algorithmic fairness, and political polarization. Prior to joining MIT, he was a faculty member at the Australian National University and the University of Sydney, and a junior research fellow at Oxford University. He received his BA from Princeton University and his PhD from MIT, both in philosophy.

Yunha Hwang is an assistant professor in the Department of Biology, holding an MIT Schwarzman College of Computing shared position with EECS. She is also a member of the Laboratory for Information and Decision Systems. Her research interests span machine learning for sustainable biomanufacturing, microbial evolution, and open science. She serves as the co-founder and chief scientist at Tatta Bio, a scientific nonprofit dedicated to advancing genomic AI for biological discovery. She holds a BS in computer science from Stanford University and a PhD in biology from Harvard University.

Ben Lindquist is an assistant professor in the History Section, holding an MIT Schwarzman College of Computing shared position with EECS. Through a historical lens, his work observes the ways that computing has circulated with ideas of religion, emotion, and divergent thinking. His book, “The Feeling Machine” (University of Chicago Press, forthcoming), follows the history of synthetic speech to examine how emotion became a subject of computer science. He was a postdoc in the Science in Human Culture Program at Northwestern University and earned his PhD in history from Princeton University.

Mariana Popescu is an assistant professor in the Department of Architecture, holding an MIT Schwarzman College of Computing shared position with EECS. She is also a member of the Computer Science and Artificial Intelligence Laboratory (CSAIL). A computational architect and structural designer, Popescu has a strong interest and experience in innovative ways of approaching the fabrication process and use of materials in construction. Her area of expertise is computational and parametric design, with a focus on digital fabrication and sustainable design. Popescu earned her doctorate at ETH Zurich.

Paris Smaragdis SM ’97, PhD ’01 is a professor in the Music and Theater Arts Section, holding an MIT Schwarzman College of Computing shared position with EECS. His research focus lies at the intersection of signal processing and machine learning, especially as it relates to sound and music. Prior to coming to MIT, he worked as a research scientist at Mitsubishi Electric Research Labs, a senior research scientist at Adobe Research, and an Amazon Scholar with Amazon’s AWS. He spent 15 years as a professor at the University of Illinois Urbana Champaign in the Computer Science Department, where he spearheaded the design of the CS+Music program, and served as an associate director of the School of Computer and Data Science. He holds a BMus from Berklee College of Music and earned his PhD in perceptual computing from MIT.

Daniel Varon is an assistant professor in the Department of Aeronautics and Astronautics, holding an MIT Schwarzman College of Computing shared position with IDSS. His work focuses on using satellite observations of atmospheric composition to better understand human impacts on the environment and identify opportunities to reduce them. An atmospheric scientist, Varon is particularly interested in greenhouse gasses, air pollution, and satellite remote sensing. He holds an MS in applied mathematics and a PhD in atmospheric chemistry, both from Harvard University.

In addition, the School of Engineering has adopted the shared faculty search model to hire its first shared faculty member:

Mark Rau is an assistant professor in the Music and Theater Arts Section, holding a School of Engineering shared position with EECS. He is involved in developing graduate programming focused on music technology. He has an interest in musical acoustics, vibration and acoustic measurement, audio signal processing, and physical modeling synthesis. His work focuses on musical instruments and creative audio effects. He holds an MA in music, science, and technology from Stanford, as well as a BS in physics and BMus in jazz from McGill University. He earned his PhD at Stanford’s Center for Computer Research in Music and Acoustics.

The new core faculty are:

Mitchell Gordon is an assistant professor in EECS. He is also a member of CSAIL. In his research, Gordon designs interactive systems and evaluation approaches that bridge principles of human-computer interaction with the realities of machine learning. His work has won awards at conferences in human-computer interaction and artificial intelligence, including a best paper award at CHI and an Oral at NeurIPS. Gordon received a BS from the University of Rochester, and MS and PhD from Stanford University, all in computer science.

Omar Khattab is an assistant professor in EECS. He is also a member of CSAIL. His work focuses on natural language processing, information retrieval, and AI systems. His research includes developing new algorithms and abstractions for declarative AI programming and for composing retrieval and reasoning. He received his BS from Carnegie Mellon University and his PhD from Stanford University, both in computer science.

Rachit Nigam will join EECS as an assistant professor in January 2026. He will also be a member of CSAIL and the Microsystems Technology Laboratories. He works on programming languages and computer architecture to address the design, verification, and usability challenges of specialized hardware. He was previously a visiting scholar at MIT. Nigam earned an MS and PhD in computer science from Cornell University.

Biologists identify targets for new pancreatic cancer treatments

Research from MIT and Dana-Farber Cancer Institute yielded hundreds of “cryptic” peptides that are found only on pancreatic tumor cells and could be targeted by vaccines or engineered T cells.

Anne Trafton | MIT News
May 7, 2025

Researchers from MIT and Dana-Farber Cancer Institute have discovered that a class of peptides expressed in pancreatic cancer cells could be a promising target for T-cell therapies and other approaches that attack pancreatic tumors.

Known as cryptic peptides, these molecules are produced from sequences in the genome that were not thought to encode proteins. Such peptides can also be found in some healthy cells, but in this study, the researchers identified about 500 that appear to be found only in pancreatic tumors.

The researchers also showed they could generate T cells targeting those peptides. Those T cells were able to attack pancreatic tumor organoids derived from patient cells, and they significantly slowed down tumor growth in a study of mice.

“Pancreas cancer is one of the most challenging cancers to treat. This study identifies an unexpected vulnerability in pancreas cancer cells that we may be able to exploit therapeutically,” says Tyler Jacks, the David H. Koch Professor of Biology at MIT and a member of the Koch Institute for Integrative Cancer Research.

Jacks and William Freed-Pastor, a physician-scientist in the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute and an assistant professor at Harvard Medical School, are the senior authors of the study, which appears today in Science. Zackery Ely PhD ’22 and Zachary Kulstad, a former research technician at Dana-Farber Cancer Institute and the Koch Institute, are the lead authors of the paper.

Cryptic peptides

Pancreatic cancer has one of the lowest survival rates of any cancer — about 10 percent of patients survive for five years after their diagnosis.

Most pancreatic cancer patients receive a combination of surgery, radiation treatment, and chemotherapy. Immunotherapy treatments such as checkpoint blockade inhibitors, which are designed to help stimulate the body’s own T cells to attack tumor cells, are usually not effective against pancreatic tumors. However, therapies that deploy T cells engineered to attack tumors have shown promise in clinical trials.

These therapies involve programming the T-cell receptor (TCR) of T cells to recognize a specific peptide, or antigen, found on tumor cells. There are many efforts underway to identify the most effective targets, and researchers have found some promising antigens that consist of mutated proteins that often show up when pancreatic cancer genomes are sequenced.

In the new study, the MIT and Dana-Farber team wanted to extend that search into tissue samples from patients with pancreatic cancer, using immunopeptidomics — a strategy that involves extracting the peptides presented on a cell surface and then identifying the peptides using mass spectrometry.

Using tumor samples from about a dozen patients, the researchers created organoids — three-dimensional growths that partially replicate the structure of the pancreas. The immunopeptidomics analysis, which was led by Jennifer Abelin and Steven Carr at the Broad Institute, found that the majority of novel antigens found in the tumor organoids were cryptic antigens. Cryptic peptides have been seen in other types of tumors, but this is the first time they have been found in pancreatic tumors.

Each tumor expressed an average of about 250 cryptic peptides, and in total, the researchers identified about 1,700 cryptic peptides.

“Once we started getting the data back, it just became clear that this was by far the most abundant novel class of antigens, and so that’s what we wound up focusing on,” Ely says.

The researchers then performed an analysis of healthy tissues to see if any of these cryptic peptides were found in normal cells. They found that about two-thirds of them were also found in at least one type of healthy tissue, leaving about 500 that appeared to be restricted to pancreatic cancer cells.

“Those are the ones that we think could be very good targets for future immunotherapies,” Freed-Pastor says.

Programmed T cells

To test whether these antigens might hold potential as targets for T-cell-based treatments, the researchers exposed about 30 of the cancer-specific antigens to immature T cells and found that 12 of them could generate large populations of T cells targeting those antigens.

The researchers then engineered a new population of T cells to express those T-cell receptors. These engineered T cells were able to destroy organoids grown from patient-derived pancreatic tumor cells. Additionally, when the researchers implanted the organoids into mice and then treated them with the engineered T cells, tumor growth was significantly slowed.

This is the first time that anyone has demonstrated the use of T cells targeting cryptic peptides to kill pancreatic tumor cells. Even though the tumors were not completely eradicated, the results are promising, and it is possible that the T-cells’ killing power could be strengthened in future work, the researchers say.

Freed-Pastor’s lab is also beginning to work on a vaccine targeting some of the cryptic antigens, which could help stimulate patients’ T cells to attack tumors expressing those antigens. Such a vaccine could include a collection of the antigens identified in this study, including those frequently found in multiple patients.

This study could also help researchers in designing other types of therapy, such as T cell engagers — antibodies that bind an antigen on one side and T cells on the other, which allows them to redirect any T cell to kill tumor cells.

Any potential vaccine or T cell therapy is likely a few years away from being tested in patients, the researchers say.

The research was funded in part by the Hale Family Center for Pancreatic Cancer Research, the Lustgarten Foundation, Stand Up To Cancer, the Pancreatic Cancer Action Network, the Burroughs Wellcome Fund, a Conquer Cancer Young Investigator Award, the National Institutes of Health, and the National Cancer Institute.

Dopamine signals when a fear can be forgotten

Study shows how a dopamine circuit between two brain regions enables mice to extinguish fear after a peril has passed.

David Orenstein | The Picower Institute for Learning and Memory
May 7, 2025

Dangers come but dangers also go, and when they do, the brain has an “all-clear” signal that teaches it to extinguish its fear. A new study in mice by MIT neuroscientists shows that the signal is the release of dopamine along a specific interregional brain circuit. The research therefore pinpoints a potentially critical mechanism of mental health, restoring calm when it works, but prolonging anxiety or even post-traumatic stress disorder when it doesn’t.

“Dopamine is essential to initiate fear extinction,” says Michele Pignatelli di Spinazzola, co-author of the new study from the lab of senior author Susumu Tonegawa, Picower Professor of biology and neuroscience at the RIKEN-MIT Laboratory for Neural Circuit Genetics within The Picower Institute for Learning and Memory at MIT, and a Howard Hughes Medical Institute (HHMI) investigator.

In 2020, Tonegawa’s lab showed that learning to be afraid, and then learning when that’s no longer necessary, result from a competition between populations of cells in the brain’s amygdala region. When a mouse learns that a place is “dangerous” (because it gets a little foot shock there), the fear memory is encoded by neurons in the anterior of the basolateral amygdala (aBLA) that express the gene Rspo2. When the mouse then learns that a place is no longer associated with danger (because they wait there and the zap doesn’t recur), neurons in the posterior basolateral amygdala (pBLA) that express the gene Ppp1r1b encode a new fear extinction memory that overcomes the original dread. Notably, those same neurons encode feelings of reward, helping to explain why it feels so good when we realize that an expected danger has dwindled.

In the new study, the lab, led by former members Xiangyu Zhang and Katelyn Flick, sought to determine what prompts these amygdala neurons to encode these memories. The rigorous set of experiments the team reports in the Proceedings of the National Academy of Sciences show that it’s dopamine sent to the different amygdala populations from distinct groups of neurons in the ventral tegmental area (VTA).

“Our study uncovers a precise mechanism by which dopamine helps the brain unlearn fear,” says Zhang, who also led the 2020 study and is now a senior associate at Orbimed, a health care investment firm. “We found that dopamine activates specific amygdala neurons tied to reward, which in turn drive fear extinction. We now see that unlearning fear isn’t just about suppressing it — it’s a positive learning process powered by the brain’s reward machinery. This opens up new avenues for understanding and potentially treating fear-related disorders, like PTSD.”

Forgetting fear

The VTA was the lab’s prime suspect to be the source of the signal because the region is well known for encoding surprising experiences and instructing the brain, with dopamine, to learn from them. The first set of experiments in the paper used multiple methods for tracing neural circuits to see whether and how cells in the VTA and the amygdala connect. They found a clear pattern: Rspo2 neurons were targeted by dopaminergic neurons in the anterior and left and right sides of the VTA. Ppp1r1b neurons received dopaminergic input from neurons in the center and posterior sections of the VTA. The density of connections was greater on the Ppp1r1b neurons than for the Rspo2 ones.

The circuit tracing showed that dopamine is available to amygdala neurons that encode fear and its extinction, but do those neurons care about dopamine? The team showed that indeed they express “D1” receptors for the neuromodulator. Commensurate with the degree of dopamine connectivity, Ppp1r1b cells had more receptors than Rspo2 neurons.

Dopamine does a lot of things, so the next question was whether its activity in the amygdala actually correlated with fear encoding and extinction. Using a method to track and visualize it in the brain, the team watched dopamine in the amygdala as mice underwent a three-day experiment. On Day One, they went to an enclosure where they experienced three mild shocks on the feet. On Day Two, they went back to the enclosure for 45 minutes, where they didn’t experience any new shocks — at first, the mice froze in anticipation of a shock, but then relaxed after about 15 minutes. On Day Three they returned again to test whether they had indeed extinguished the fear they showed at the beginning of Day Two.

The dopamine activity tracking revealed that during the shocks on Day One, Rspo2 neurons had the larger response to dopamine, but in the early moments of Day Two, when the anticipated shocks didn’t come and the mice eased up on freezing, the Ppp1r1b neurons showed the stronger dopamine activity. More strikingly, the mice that learned to extinguish their fear most strongly also showed the greatest dopamine signal at those neurons.

Causal connections

The final sets of experiments sought to show that dopamine is not just available and associated with fear encoding and extinction, but also actually causes them. In one set, they turned to optogenetics, a technology that enables scientists to activate or quiet neurons with different colors of light. Sure enough, when they quieted VTA dopaminergic inputs in the pBLA, doing so impaired fear extinction. When they activated those inputs, it accelerated fear extinction. The researchers were surprised that when they activated VTA dopaminergic inputs into the aBLA they could reinstate fear even without any new foot shocks, impairing fear extinction.

The other way they confirmed a causal role for dopamine in fear encoding and extinction was to manipulate the amygdala neurons’ dopamine receptors. In Ppp1r1b neurons, over-expressing dopamine receptors impaired fear recall and promoted extinction, whereas knocking the receptors down impaired fear extinction. Meanwhile in the Rspo2 cells, knocking down receptors reduced the freezing behavior.

“We showed that fear extinction requires VTA dopaminergic activity in the pBLA Ppp1r1b neurons by using optogenetic inhibition of VTA terminals and cell-type-specific knockdown of D1 receptors in these neurons,” the authors wrote.

The scientists are careful in the study to note that while they’ve identified the “teaching signal” for fear extinction learning, the broader phenomenon of fear extinction occurs brainwide, rather than in just this single circuit.

But the circuit seems to be a key node to consider as drug developers and psychiatrists work to combat anxiety and PTSD, Pignatelli di Spinazzola says.

“Fear learning and fear extinction provide a strong framework to study generalized anxiety and PTSD,” he says. “Our study investigates the underlying mechanisms suggesting multiple targets for a translational approach, such as pBLA and use of dopaminergic modulation.”

Marianna Rizzo is also a co-author of the study. Support for the research came from the RIKEN Center for Brain Science, the HHMI, the Freedom Together Foundation, and The Picower Institute.

Staff Spotlight: Lighting up biology’s basement lab

Senior Technical Instructor Vanessa Cheung ’02 brings the energy, experience, and excitement needed to educate students in the biology teaching lab.

Samantha Edelen | Department of Biology
April 29, 2025

For more than 30 years, Course 7 (Biology) students have descended to the expansive, windowless basement of Building 68 to learn practical skills that are the centerpiece of undergraduate biology education at the Institute. The lines of benches and cabinets of supplies that make up the underground MIT Biology Teaching Lab could easily feel dark and isolated.

In the corner of this room, however, sits Senior Technical Instructor Vanessa Cheung ’02, who manages to make the space seem sunny and communal.

“We joke that we could rig up a system of mirrors to get just enough daylight to bounce down from the stairwell,” Cheung says with a laugh. “It is a basement, but I am very lucky to have this teaching lab space. It is huge and has everything we need.”

This optimism and gratitude fostered by Cheung is critical, as MIT undergrad students enrolled in classes 7.002 (Fundamentals of Experimental Molecular Biology) and 7.003 (Applied Molecular Biology Laboratory) spend four-hour blocks in the lab each week, learning the foundations of laboratory technique and theory for biological research from Cheung and her colleagues.

Running toward science education

Cheung’s love for biology can be traced back to her high school cross country and track coach, who also served as her second-year biology teacher. The sport and the fundamental biological processes she was learning about in the classroom were, in fact, closely intertwined.

“He told us about how things like ATP [adenosine triphosphate] and the energy cycle would affect our running,” she says. “Being able to see that connection really helped my interest in the subject.”

That inspiration carried her through a move from her hometown of Pittsburgh, Pennsylvania, to Cambridge, Massachusetts, to pursue an undergraduate degree at MIT, and through her thesis work to earn a PhD in genetics at Harvard Medical School. She didn’t leave running behind either: To this day, she can often be found on the Charles River Esplanade, training for her next marathon.

She discovered her love of teaching during her PhD program. She enjoyed guiding students so much that she spent an extra semester as a teaching assistant, outside of the one required for her program.

“I love research, but I also really love telling people about research,” Cheung says.

Cheung herself describes lab instruction as the “best of both worlds,” enabling her to pursue her love of teaching while spending every day at the bench, doing experiments. She emphasizes for students the importance of being able not just to do the hands-on technical lab work, but also to understand the theory behind it.

“The students can tend to get hung up on the physical doing of things — they are really concerned when their experiments don’t work,” she says. “We focus on teaching students how to think about being in a lab — how to design an experiment and how to analyze the data.”

Although her talent for teaching and passion for science led her to the role, Cheung doesn’t hesitate to identify the students as her favorite part of the job.

“It sounds cheesy, but they really do keep the job very exciting,” she says.

Using mind and hand in the lab

Cheung is the type of person who lights up when describing how much she “loves working with yeast.”

“I always tell the students that maybe no one cares about yeast except me and like three other people in the world, but it is a model organism that we can use to apply what we learn to humans,” Cheung explains.

Though mastering basic lab skills can make hands-on laboratory courses feel “a bit cookbook,” Cheung is able to get the students excited with her enthusiasm and clever curriculum design.

“The students like things where they can get their own unique results, and things where they have a little bit of freedom to design their own experiments,” she says. So, the lab curriculum incorporates opportunities for students to do things like identify their own unique yeast mutants and design their own questions to test in a chemical engineering module.

Part of what makes theory as critical as technique is that new tools and discoveries are made frequently in biology, especially at MIT. For example, there has been a shift from a focus on RNAi to CRISPR as a popular lab technique in recent years, and Cheung muses that CRISPR itself may be overshadowed within only a few more years — keeping students learning at the cutting edge of biology is always on Cheung’s mind.

“Vanessa is the heart, soul, and mind of the biology lab courses here at MIT, embodying ‘mens et manus’ [‘mind and hand’],” says technical lab instructor and Biology Teaching Lab Manager Anthony Fuccione.

Support for all students

Cheung’s ability to mentor and guide students earned her a School of Science Dean’s Education and Advising Award in 2012, but her focus isn’t solely on MIT undergraduate students.

In fact, according to Cheung, the earlier students can be exposed to science, the better. In addition to her regular duties, Cheung also designs curriculum and teaches in the LEAH Knox Scholars Program. The two-year program provides lab experience and mentorship for low-income Boston- and Cambridge-area high school students.

Paloma Sanchez-Jauregui, outreach programs coordinator who works with Cheung on the program, says Cheung has a standout “growth mindset” that students really appreciate.

“Vanessa teaches students that challenges — like unexpected PCR results — are part of the learning process,” Sanchez-Jauregui says. “Students feel comfortable approaching her for help troubleshooting experiments or exploring new topics.”

Cheung’s colleagues report that they admire not only her talents, but also her focus on supporting those around her. Technical Instructor and colleague Eric Chu says Cheung “offers a lot of help to me and others, including those outside of the department, but does not expect reciprocity.”

Professor of biology and co-director of the Department of Biology undergraduate program Adam Martin says he “rarely has to worry about what is going on in the teaching lab.” According to Martin, Cheung is ”flexible, hard-working, dedicated, and resilient, all while being kind and supportive to our students. She is a joy to work with.”

Staff Spotlight: Always looking to home

Mingmar Sherpa, a researcher in the Martin Lab in the Department of Biology, has remained connected to his home in Nepal at every step of his career.

Ekaterina Khalizeva | Department of Biology
April 29, 2025

For Mingmar Sherpa, a senior research support associate in the Martin Lab in the Department of Biology, community is more than just his colleagues in the lab, where he studies how mechanical forces affect cell division timing during embryogenesis. On his long and winding path to MIT, he never left behind the people he grew up among in Nepal. Sherpa has been dedicated, every step of his career — from rural Solukhumbu to Kathmandu to Alabama to Cambridge — to advancing education and health care among his people in any way he can.

Despite working more than 7,000 miles away from home, Mingmar Sherpa makes every effort to keep himself connected to his community in Nepal. Every month, for example, he sends home money to support a computer lab that he established in his hometown in rural Solukhumbu, the district of Nepal that houses Mount Everest — just $250 a month covers the costs of a teacher’s salary, electricity, internet, and a space to teach. In this lab, almost 250 students thus far have learned computer skills essential to working in today’s digitally driven world. In college, Sherpa also started The Bright Vision Foundation (The Bright Future), an organization to support health and education in Nepal, and during the pandemic raised funds to provide personal protective equipment (PPE) and health care services across his home country.

While Sherpa’s ambition to help his home can be traced back to his childhood, he didn’t have it all figured out from the start, and found inspiration at each step of his career.

“This mindset of giving back to the community, helping policymakers or establishing an organization to help people do science, helping the scientific community to find cures for diseases — all these ideas came to me along the way,” Sherpa says. “It is the journey that matters.”

A journey driven by hope and optimism

“Sherpa” is a reference to the ethnic group native to the mountainous regions of Nepal and Tibet, whose members are well-known for their mountaineering skills, which they use to guide and assist tourists who want to climb Mount Everest. Growing up in rural Solukhumbu, Sherpa was surrounded by people working in the tourism industry; few other occupations appeared feasible. There was just one hospital for the whole district, requiring locals to walk for days to get medical assistance.

The youngest of seven siblings, Sherpa went to an English-language middle school, which he had to walk for over an hour to get to. He excelled there, soon becoming the top student in his class and passing the national exam with distinction — success that allowed him to both dream of and accomplish a move to Kathmandu, the capital city of Nepal, to study in the best school in the country.

It was an overwhelming transition, surrounded as he was for the first time by people from a very different social class, privileged with far more technological resources. The gaps between this well-equipped community and the one he left back home became increasingly obvious and left a strong impression on Sherpa.

There, he started thinking about how to use his newly acquired access to education and technology to uplift his community at home. He was especially fascinated by questions surrounding biology and human health, and next set his sights on attending college in the United States.

“If I came to the U.S., I could learn skills which I could not learn in Nepal,” he says. “I could prepare myself to solve the problems that I want to solve.”

At the University of Alabama in Birmingham, Sherpa continued to deepen his passion for biological science and joined a research lab. Through that work, he discovered the joys of basic research and the diverse set of skills it fosters.

“I joined the lab to learn science, but to do science, you need other skills, like research communication,” he says. “I was learning unintentionally from being in a research position.”

When Covid-19 spread around the globe, Sherpa wanted to apply the expertise and resources he had gained to help his people address the crisis. It was then that he started The Bright Vision Foundation, an organization aiming to raise the standards of health care and education in underserved communities in Nepal. Through the foundation, he raised funds to distribute PPE, provide health care services, and set up the computer lab in his childhood home.

“Today’s world is all about technology and innovation, but here are good people in my community who don’t even know about computers,” he says.

With the help of his brother, who serves as the lab instructor, and his parents, who provide the space and support the lab, and Sherpa’s own fundraising, he aims to help youths from backgrounds similar to his own be better prepared for the technologically advanced, globalized world of today.

The MIT chapter

Now, at MIT, Sherpa speaks with deep appreciation of the opportunities that the university has opened up for him — the people he has been meeting here, and the skills he has been learning.

Professor of biology Adam C. Martin, Sherpa’s principal investigator, views making sure that international trainees like Mingmar are aware of the wide range of opportunities MIT offers — whether it be workshops, collaborations, networking and funding possibilities, or help with the pathway toward graduate school — as a key part of creating a supportive environment.

Understanding the additional burdens on international trainees gives Martin extra appreciation for Sherpa’s perseverance, motivation, and desire to share his culture with the lab, sharing Nepalese food and providing context for Nepalese customs.

Being at such a research-intensive institution as MIT has helped Sherpa further clarify his goals and his view of the paths he can take to achieve them. Since college, his three passions have been intertwined: leadership, research, and human health.

Sherpa will pursue a PhD in biomedical and biological sciences with a focus in cancer biology at Cornell University in the fall. In the longer term, he plans to focus on developing policy to improve public health.

Although Sherpa recognizes that Nepal is not the only place that might need his help, he has a sharp focus and an acute sense of what he is best positioned to do now. Sherpa is gearing up to organize a health camp in the spring to bring doctors to rural areas in Nepal, not only to provide care, but also to gather data on nutrition and health in different regions of the country.

“I cannot, in a day, or even a year, bring the living conditions of people in vulnerable communities up to a higher level, but I can slowly increase the living standard of people in less-developed communities, especially in Nepal,” he says. “There might be other parts of the world which are even more vulnerable than Nepal, but I haven’t explored them yet. But I know my community in Nepal, so I want to help improve people’s lives there.”

New study reveals how cleft lip and cleft palate can arise

MIT biologists have found that defects in some transfer RNA molecules can lead to the formation of these common conditions.

Anne Trafton | MIT News
April 17, 2025

Cleft lip and cleft palate are among the most common birth defects, occurring in about one in 1,050 births in the United States. These defects, which appear when the tissues that form the lip or the roof of the mouth do not join completely, are believed to be caused by a mix of genetic and environmental factors.

In a new study, MIT biologists have discovered how a genetic variant often found in people with these facial malformations leads to the development of cleft lip and cleft palate.

Their findings suggest that the variant diminishes cells’ supply of transfer RNA, a molecule that is critical for assembling proteins. When this happens, embryonic face cells are unable to fuse to form the lip and roof of the mouth.

“Until now, no one had made the connection that we made. This particular gene was known to be part of the complex involved in the splicing of transfer RNA, but it wasn’t clear that it played such a crucial role for this process and for facial development. Without the gene, known as DDX1, certain transfer RNA can no longer bring amino acids to the ribosome to make new proteins. If the cells can’t process these tRNAs properly, then the ribosomes can’t make protein anymore,” says Michaela Bartusel, an MIT research scientist and the lead author of the study.

Eliezer Calo, an associate professor of biology at MIT, is the senior author of the paper, which appears today in the American Journal of Human Genetics.

Genetic variants

Cleft lip and cleft palate, also known as orofacial clefts, can be caused by genetic mutations, but in many cases, there is no known genetic cause.

“The mechanism for the development of these orofacial clefts is unclear, mostly because they are known to be impacted by both genetic and environmental factors,” Calo says. “Trying to pinpoint what might be affected has been very challenging in this context.”

To discover genetic factors that influence a particular disease, scientists often perform genome-wide association studies (GWAS), which can reveal variants that are found more often in people who have a particular disease than in people who don’t.

For orofacial clefts, some of the genetic variants that have regularly turned up in GWAS appeared to be in a region of DNA that doesn’t code for proteins. In this study, the MIT team set out to figure out how variants in this region might influence the development of facial malformations.

Their studies revealed that these variants are located in an enhancer region called e2p24.2. Enhancers are segments of DNA that interact with protein-coding genes, helping to activate them by binding to transcription factors that turn on gene expression.

The researchers found that this region is in close proximity to three genes, suggesting that it may control the expression of those genes. One of those genes had already been ruled out as contributing to facial malformations, and another had already been shown to have a connection. In this study, the researchers focused on the third gene, which is known as DDX1.

DDX1, it turned out, is necessary for splicing transfer RNA (tRNA) molecules, which play a critical role in protein synthesis. Each transfer RNA molecule transports a specific amino acid to the ribosome — a cell structure that strings amino acids together to form proteins, based on the instructions carried by messenger RNA.

While there are about 400 different tRNAs found in the human genome, only a fraction of those tRNAs require splicing, and those are the tRNAs most affected by the loss of DDX1. These tRNAs transport four different amino acids, and the researchers hypothesize that these four amino acids may be particularly abundant in proteins that embryonic cells that form the face need to develop properly.

When the ribosomes need one of those four amino acids, but none of them are available, the ribosome can stall, and the protein doesn’t get made.

The researchers are now exploring which proteins might be most affected by the loss of those amino acids. They also plan to investigate what happens inside cells when the ribosomes stall, in hopes of identifying a stress signal that could potentially be blocked and help cells survive.

Malfunctioning tRNA

While this is the first study to link tRNA to craniofacial malformations, previous studies have shown that mutations that impair ribosome formation can also lead to similar defects. Studies have also shown that disruptions of tRNA synthesis — caused by mutations in the enzymes that attach amino acids to tRNA, or in proteins involved in an earlier step in tRNA splicing — can lead to neurodevelopmental disorders.

“Defects in other components of the tRNA pathway have been shown to be associated with neurodevelopmental disease,” Calo says. “One interesting parallel between these two is that the cells that form the face are coming from the same place as the cells that form the neurons, so it seems that these particular cells are very susceptible to tRNA defects.”

The researchers now hope to explore whether environmental factors linked to orofacial birth defects also influence tRNA function. Some of their preliminary work has found that oxidative stress — a buildup of harmful free radicals — can lead to fragmentation of tRNA molecules. Oxidative stress can occur in embryonic cells upon exposure to ethanol, as in fetal alcohol syndrome, or if the mother develops gestational diabetes.

“I think it is worth looking for mutations that might be causing this on the genetic side of things, but then also in the future, we would expand this into which environmental factors have the same effects on tRNA function, and then see which precautions might be able to prevent any effects on tRNAs,” Bartusel says.

The research was funded by the National Science Foundation Graduate Research Program, the National Cancer Institute, the National Institute of General Medical Sciences, and the Pew Charitable Trusts.

Restoring healthy gene expression with programmable therapeutics

CAMP4 Therapeutics is targeting regulatory RNA, whose role in gene expression was first described by co-founder and MIT Professor Richard Young.

Zach Winn | MIT News
April 16, 2025

Many diseases are caused by dysfunctional gene expression that leads to too much or too little of a given protein. Efforts to cure those diseases include everything from editing genes to inserting new genetic snippets into cells to injecting the missing proteins directly into patients.

CAMP4 is taking a different approach. The company is targeting a lesser-known player in the regulation of gene expression known as regulatory RNA. CAMP4 co-founder and MIT Professor Richard Young has shown that by interacting with molecules called transcription factors, regulatory RNA plays an important role in controlling how genes are expressed. CAMP4’s therapeutics target regulatory RNA to increase the production of proteins and put patients’ levels back into healthy ranges.

The company’s approach holds promise for treating diseases caused by defects in gene expression, such as metabolic diseases, heart conditions, and neurological disorders. Targeting regulatory RNAs as opposed to genes could also offer more precise treatments than existing approaches.

“If I just want to fix a single gene’s defective protein output, I don’t want to introduce something that makes that protein at high, uncontrolled amounts,” says Young, who is also a core member of the Whitehead Institute. “That’s a huge advantage of our approach: It’s more like a correction than sledgehammer.”

CAMP4’s lead drug candidate targets urea cycle disorders (UCDs), a class of chronic conditions caused by a genetic defect that limits the body’s ability to metabolize and excrete ammonia. A phase 1 clinical trial has shown CAMP4’s treatment is safe and tolerable for humans, and in preclinical studies the company has shown its approach can be used to target specific regulatory RNA in the cells of humans with UCDs to restore gene expression to healthy levels.

“This has the potential to treat very severe symptoms associated with UCDs,” says Young, who co-founded CAMP4 with cancer genetics expert Leonard Zon, a professor at Harvard Medical School. “These diseases can be very damaging to tissues and causes a lot of pain and distress. Even a small effect in gene expression could have a huge benefit to patients, who are generally young.”

Mapping out new therapeutics

Young, who has been a professor at MIT since 1984, has spent decades studying how genes are regulated. It’s long been known that molecules called transcription factors, which orchestrate gene expression, bind to DNA and proteins. Research published in Young’s lab uncovered a previously unknown way in which transcription factors can also bind to RNA. The finding indicated RNA plays an underappreciated role in controlling gene expression.

CAMP4 was founded in 2016 with the initial idea of mapping out the signaling pathways that govern the expression of genes linked to various diseases. But as Young’s lab discovered and then began to characterize the role of regulatory RNA in gene expression around 2020, the company pivoted to focus on targeting regulatory RNA using therapeutic molecules known as antisense oligonucleotides (ASOs), which have been used for years to target specific messenger RNA sequences.

CAMP4 began mapping the active regulatory RNAs associated with the expression of every protein-coding gene and built a database, which it calls its RAP Platform, that helps it quickly identify regulatory RNAs to target  specific diseases and select ASOs that will most effectively bind to those RNAs.

Today, CAMP4 is using its platform to develop therapeutic candidates it believes can restore healthy protein levels to patients.

“The company has always been focused on modulating gene expression,” says CAMP4 Chief Financial Officer Kelly Gold MBA ’09. “At the simplest level, the foundation of many diseases is too much or too little of something being produced by the body. That is what our approach aims to correct.”

Accelerating impact

CAMP4 is starting by going after diseases of the liver and the central nervous system, where the safety and efficacy of ASOs has already been proven. Young believes correcting genetic expression without modulating the genes themselves will be a powerful approach to treating a range of complex diseases.

“Genetics is a powerful indicator of where a deficiency lies and how you might reverse that problem,” Young says. “There are many syndromes where we don’t have a complete understanding of the underlying mechanism of disease. But when a mutation clearly affects the output of a gene, you can now make a drug that can treat the disease without that complete understanding.”

As the company continues mapping the regulatory RNAs associated with every gene, Gold hopes CAMP4 can eventually minimize its reliance on wet-lab work and lean more heavily on machine learning to leverage its growing database and quickly identify regRNA targets for every disease it wants to treat.

In addition to its trials in urea cycle disorders, the company plans to launch key preclinical safety studies for a candidate targeting seizure disorders with a genetic basis, this year. And as the company continues exploring drug development efforts around the thousands of genetic diseases where increasing protein levels are can have a meaningful impact, it’s also considering collaborating with others to accelerate its impact.

“I can conceive of companies using a platform like this to go after many targets, where partners fund the clinical trials and use CAMP4 as an engine to target any disease where there’s a suspicion that gene upregulation or downregulation is the way to go,” Young says.

At the core of problem-solving

Stuart Levine ’97, director of MIT’s BioMicro Center, keeps departmental researchers at the forefront of systems biology.

Samantha Edelen | Department of Biology
March 19, 2025

As director of the MIT BioMicro Center (BMC), Stuart Levine ’97 wholeheartedly embraces the variety of challenges he tackles each day. One of over 50 core facilities providing shared resources across the Institute, the BMC supplies integrated high-throughput genomics, single-cell and spatial transcriptomic analysis, bioinformatics support, and data management to researchers across MIT.

“Every day is a different day,” Levine says, “there are always new problems, new challenges, and the technology is continuing to move at an incredible pace.” After more than 15 years in the role, Levine is grateful that the breadth of his work allows him to seek solutions for so many scientific problems.

By combining bioinformatics expertise with biotech relationships and a focus on maximizing the impact of the center’s work, Levine brings the broad range of skills required to match the diversity of questions asked by researchers in MIT’s Department of Biology.

Expansive expertise

Biology first appealed to Levine as an MIT undergraduate taking class 7.012 (Introduction to Biology), thanks to the charisma of instructors Professor Eric Lander and Amgen Professor Emerita Nancy Hopkins. After earning his PhD in biochemistry from Harvard University and Massachusetts General Hospital, Levine returned to MIT for postdoctoral work with Professor Richard Young, core member at the Whitehead Institute for Biomedical Research.

In the Young Lab, Levine found his calling as an informaticist and ultimately decided to stay at MIT. Here, his work has a wide-ranging impact: the BMC serves over 100 labs annually, from the the Computer Science and Artificial Intelligence Laboratory and the departments of Brain and Cognitive Sciences; Earth, Atmospheric and Planetary Sciences; Chemical Engineering; Mechanical Engineering; and, of course, Biology.

“It’s a fun way to think about science,” Levine says, noting that he applies his knowledge and streamlines workflows across these many disciplines by “truly and deeply understanding the instrumentation complexities.”

This depth of understanding and experience allows Levine to lead what longtime colleague Professor Laurie Boyer describes as “a state-of-the-art core that has served so many faculty and provides key training opportunities for all.” He and his team work with cutting-edge, finely tuned scientific instruments that generate vast amounts of bioinformatics data, then use powerful computational tools to store, organize, and visualize the data collected, contributing to research on topics ranging from host-parasite interactions to proposed tools for NASA’s planetary protection policy.

Staying ahead of the curve

With a scientist directing the core, the BMC aims to enable researchers to “take the best advantage of systems biology methods,” says Levine. These methods use advanced research technologies to do things like prepare large sets of DNA and RNA for sequencing, read DNA and RNA sequences from single cells, and localize gene expression to specific tissues.

Levine presents a lightweight, clear rectangle about the width of a cell phone and the length of a VHS cassette.

“This is a flow cell that can do 20 human genomes to clinical significance in two days — 8 billion reads,” he says. “There are newer instruments with several times that capacity available as well.”

The vast majority of research labs do not need that kind of power, but the Institute, and its researchers as a whole, certainly do. Levine emphasizes that “the ROI [return on investment] for supporting shared resources is extremely high because whatever support we receive impacts not just one lab, but all of the labs we support. Keeping MIT’s shared resources at the bleeding edge of science is critical to our ability to make a difference in the world.”

To stay at the edge of research technology, Levine maintains company relationships, while his scientific understanding allows him to educate researchers on what is possible in the space of modern systems biology. Altogether, these attributes enable Levine to help his researcher clients “push the limits of what is achievable.”

The man behind the machines

Each core facility operates like a small business, offering specialized services to a diverse client base across academic and industry research, according to Amy Keating, Jay A. Stein (1968) Professor of Biology and head of the Department of Biology. She explains that “the PhD-level education and scientific and technological expertise of MIT’s core directors are critical to the success of life science research at MIT and beyond.”

While Levine clearly has the education and expertise, the success of the BMC “business” is also in part due to his tenacity and focus on results for the core’s users.

He was recognized by the Institute with the MIT Infinite Mile Award in 2015 and the MIT Excellence Award in 2017, for which one nominator wrote, “What makes Stuart’s leadership of the BMC truly invaluable to the MIT community is his unwavering dedication to producing high-quality data and his steadfast persistence in tackling any type of troubleshooting needed for a project. These attributes, fostered by Stuart, permeate the entire culture of the BMC.”

“He puts researchers and their research first, whether providing education, technical services, general tech support, or networking to collaborators outside of MIT,” says Noelani Kamelamela, lab manager of the BMC. “It’s all in service to users and their projects.”

Tucked into the far back corner of the BMC lab space, Levine’s office is a fitting symbol of his humility. While his guidance and knowledge sit at the center of what elevates the BMC beyond technical support, he himself sits away from the spotlight, resolutely supporting others to advance science.

“Stuart has always been the person, often behind the scenes, that pushes great science, ideas, and people forward,” Boyer says. “His knowledge and advice have truly allowed us to be at the leading edge in our work.”

Helping the immune system attack tumors

Stefani Spranger is working to discover why some cancers don’t respond to immunotherapy, in hopes of making them more vulnerable to it.

Anne Trafton | MIT News
February 26, 2025

In addition to patrolling the body for foreign invaders, the immune system also hunts down and destroys cells that have become cancerous or precancerous. However, some cancer cells end up evading this surveillance and growing into tumors.

Once established, tumor cells often send out immunosuppressive signals, which leads T cells to become “exhausted” and unable to attack the tumor. In recent years, some cancer immunotherapy drugs have shown great success in rejuvenating those T cells so they can begin attacking tumors again.

While this approach has proven effective against cancers such as melanoma, it doesn’t work as well for others, including lung and ovarian cancer. MIT Associate Professor Stefani Spranger is trying to figure out how those tumors are able to suppress immune responses, in hopes of finding new ways to galvanize T cells into attacking them.

“We really want to understand why our immune system fails to recognize cancer,” Spranger says. “And I’m most excited about the really hard-to-treat cancers because I think that’s where we can make the biggest leaps.”

Her work has led to a better understanding of the factors that control T-cell responses to tumors, and raised the possibility of improving those responses through vaccination or treatment with immune-stimulating molecules called cytokines.

“We’re working on understanding what exactly the problem is, and then collaborating with engineers to find a good solution,” she says.

Jumpstarting T cells

As a student in Germany, where students often have to choose their college major while still in high school, Spranger envisioned going into the pharmaceutical industry and chose to major in biology. At Ludwig Maximilian University in Munich, her course of study began with classical biology subjects such as botany and zoology, and she began to doubt her choice. But, once she began taking courses in cell biology and immunology, her interest was revived and she continued into a biology graduate program at the university.

During a paper discussion class early in her graduate school program, Spranger was assigned to a Science paper on a promising new immunotherapy treatment for melanoma. This strategy involves isolating tumor-infiltrating T-cells during surgery, growing them into large numbers, and then returning them to the patient. For more than 50 percent of those patients, the tumors were completely eliminated.

“To me, that changed the world,” Spranger recalls. “You can take the patient’s own immune system, not really do all that much to it, and then the cancer goes away.”

Spranger completed her PhD studies in a lab that worked on further developing that approach, known as adoptive T-cell transfer therapy. At that point, she still was leaning toward going into pharma, but after finishing her PhD in 2011, her husband, also a biologist, convinced her that they should both apply for postdoc positions in the United States.

They ended up at the University of Chicago, where Spranger worked in a lab that studies how the immune system responds to tumors. There, she discovered that while melanoma is usually very responsive to immunotherapy, there is a small fraction of melanoma patients whose T cells don’t respond to the therapy at all. That got her interested in trying to figure out why the immune system doesn’t always respond to cancer the way that it should, and in finding ways to jumpstart it.

During her postdoc, Spranger also discovered that she enjoyed mentoring students, which she hadn’t done as a graduate student in Germany. That experience drew her away from going into the pharmaceutical industry, in favor of a career in academia.

“I had my first mentoring teaching experience having an undergrad in the lab, and seeing that person grow as a scientist, from barely asking questions to running full experiments and coming up with hypotheses, changed how I approached science and my view of what academia should be for,” she says.

Modeling the immune system

When applying for faculty jobs, Spranger was drawn to MIT by the collaborative environment of MIT and its Koch Institute for Integrative Cancer Research, which offered the chance to collaborate with a large community of engineers who work in the field of immunology.

“That community is so vibrant, and it’s amazing to be a part of it,” she says.

Building on the research she had done as a postdoc, Spranger wanted to explore why some tumors respond well to immunotherapy, while others do not. For many of her early studies, she used a mouse model of non-small-cell lung cancer. In human patients, the majority of these tumors do not respond well to immunotherapy.

“We build model systems that resemble each of the different subsets of non-responsive non-small cell lung cancer, and we’re trying to really drill down to the mechanism of why the immune system is not appropriately responding,” she says.

As part of that work, she has investigated why the immune system behaves differently in different types of tissue. While immunotherapy drugs called checkpoint inhibitors can stimulate a strong T-cell response in the skin, they don’t do nearly as much in the lung. However, Spranger has shown that T cell responses in the lung can be improved when immune molecules called cytokines are also given along with the checkpoint inhibitor.

Those cytokines work, in part, by activating dendritic cells — a class of immune cells that help to initiate immune responses, including activation of T cells.

“Dendritic cells are the conductor for the orchestra of all the T cells, although they’re a very sparse cell population,” Spranger says. “They can communicate which type of danger they sense from stressed cells and then instruct the T cells on what they have to do and where they have to go.”

Spranger’s lab is now beginning to study other types of tumors that don’t respond at all to immunotherapy, including ovarian cancer and glioblastoma. Both the brain and the peritoneal cavity appear to suppress T-cell responses to tumors, and Spranger hopes to figure out how to overcome that immunosuppression.

“We’re specifically focusing on ovarian cancer and glioblastoma, because nothing’s working right now for those cancers,” she says. “We want to understand what we have to do in those sites to induce a really good anti-tumor immune response.”