Sean Luk: Addressing the urgent need for better immunotherapy

In elementary school, Sean Luk loved donning an oversized lab coat and helping her mom pipette chemicals at Johns Hopkins University. A few years later, she started a science blog and became fascinated by immunoengineering, which is now her concentration as a biological engineering major at MIT.

Her grandparents’ battles with cancer made Luk, now a senior, realize how urgently patients need advancements in immunotherapy, which leverages a patient’s immune system to fight tumors or pathogens.

“The idea of creating something that is actually able to improve human health is what really drives me now. You want to fight that sense of helplessness when you see a loved one suffering through this disease, and it just further motivates me to be excellent at what I do,” Luk says.

A varsity athlete and entrepreneur as well as a researcher, Luk thrives when bringing people together for a common cause.

Working with immunotherapies

Luk was introduced to immunotherapies in high school after she listened to a seminar about using components of the immune system, such as antibodies and cytokines, to improve graft tolerance.

“The complexity of the immune system really fascinated me, and it is incredible that we can build antibodies in a very logical way to address disease,” Luk says.

She worked in several Johns Hopkins labs as a high school student in Maryland, and a professor there connected her to MIT Professor Dane Wittrup. Luk has worked in the Wittrup lab throughout her time at MIT. One of her main projects involves developing ultra-stable cyclic peptide drugs to help treat autoimmune diseases, which could potentially be taken orally instead of injected.

Luk has been a co-author on two published articles and has become increasingly interested in the intersection between computational and experimental protein design. Currently, she is working on engineering an interferon gamma construct that preferentially targets myeloid cells in the tumor microenvironment.

“We're trying to target and reprogram the immunosuppressive myeloid cells surrounding the cancer cells, so that they can license T cells to attack cancer cells and kickstart the cancer immunity cycle,” she explains.

Communication for all

Through her work in high school with Best Buddies, an organization that aims to promote one-on-one friendships between students with and without intellectual and developmental disabilities, Luk became passionate about empowering people with special needs. At MIT, she started a project focusing on children with Down syndrome, with support from the Sandbox Innovation Fund.

“Through talking to a lot of parents and caretakers, the biggest issue that people with Down syndrome face is communication. And when you think about it, communication is crucial to everything that we do,” Luk says, “We want to communicate our thoughts. We want to be able to interact with our peers. And if people are unable to do that, it’s isolating, it’s frustrating.”

Her solution was to co-found EasyComm, an online game platform that helps children with Down syndrome work on verbal communication.

“We thought it would be a great way to improve their verbal communication skills while having fun and incentivize that kind of learning through gamification,” Luk says. She and her co-founder recently filed a provisional patent and plan to make the platform available to a wider audience.

A global perspective

Luk grew up in Hong Kong before moving to Maryland in the fifth grade. She’s always been athletic; in Hong Kong, she was a competitive jump roper. At just 9 years old, she won bronze in the Asian Jump Rope Championships among children 14 years old and younger. At 7 years old, she started playing soccer on her brother’s team, despite being the only girl. She says the sport was considered “manly” in Hong Kong, and girls were discouraged from joining, but her coaches and family were supportive.

Moving to the U.S. meant that her time in competitive jump roping was cut short, and Luk focused more on soccer. Her team in the U.S. felt far more intense than boys soccer in Hong Kong, but the Luk family was in it together, Luk says. She credits her success to the combination of her hard-working nature she learned from Hong Kong, and the innovation and experiences she was exposed to in the U.S.

“We had a really close bond within the family,” Luk says, “Figuring out taxes for my dad and our family, like driving and houses and all that stuff, it was totally new. But I think we really took it in stride, just adjusting as we went.”

Luk continued soccer throughout high school and eventually committed to play on the MIT team. She likes that the team allows players to prioritize academics while still being competitive. Last season, she was elected captain.

“It’s really a pleasure to be captain, and it’s challenging, but it’s also very rewarding when you see the team be cohesive. When you see the team out there winning games through grit,” Luk says.

During her first year at MIT, Luk got back in touch with her old soccer coach from Hong Kong, who then worked on the national team. After sending over some tape, she was offered a spot on the U-20 national team, and played in the U20 Asian Football Championship Qualifiers.

“It was so, so cool to be able to represent Hong Kong because I played soccer all my life but it just carries a different weight to it when you’re wearing your country’s jersey,” Luk says.

Besides her cross-cultural background, Luk is also proud of her international experiences playing soccer, staying with host families and doing lab work in Copenhagen, Denmark; Stuttgart, Germany; and Ancona, Italy. She speaks English, Cantonese, and Mandarin fluently.

“Aside from the textbook academic knowledge, I feel like a global perspective is so important when you’re trying to collaborate with other people from different walks of life,” Luk says, “When you’re just thinking about science or the impact that you can have in general, it’s important to realize you don’t have all the answers and to learn from the world outside your little bubble.”

de MIT News https://ift.tt/25W1KSV

MIT scientists investigate memorization risk in the age of clinical AI

What is patient privacy for? The Hippocratic Oath, thought to be one of the earliest and most widely known medical ethics texts in the world, reads: “Whatever I see or hear in the lives of my patients, whether in connection with my professional practice or not, which ought not to be spoken of outside, I will keep secret, as considering all such things to be private.” 

As privacy becomes increasingly scarce in the age of data-hungry algorithms and cyberattacks, medicine is one of the few remaining domains where confidentiality remains central to practice, enabling patients to trust their physicians with sensitive information.

But a paper co-authored by MIT researchers investigates how artificial intelligence models trained on de-identified electronic health records (EHRs) can memorize patient-specific information. The work, which was recently presented at the 2025 Conference on Neural Information Processing Systems (NeurIPS), recommends a rigorous testing setup to ensure targeted prompts cannot reveal information, emphasizing that leakage must be evaluated in a health care context to determine whether it meaningfully compromises patient privacy.

Foundation models trained on EHRs should normally generalize knowledge to make better predictions, drawing upon many patient records. But in “memorization,” the model draws upon a singular patient record to deliver its output, potentially violating patient privacy. Notably, foundation models are already known to be prone to data leakage.

“Knowledge in these high-capacity models can be a resource for many communities, but adversarial attackers can prompt a model to extract information on training data,” says Sana Tonekaboni, a postdoc at the Eric and Wendy Schmidt Center at the Broad Institute of MIT and Harvard and first author of the paper. Given the risk that foundation models could also memorize private data, she notes, “this work is a step towards ensuring there are practical evaluation steps our community can take before releasing models.”

To conduct research on the potential risk EHR foundation models could pose in medicine, Tonekaboni approached MIT Associate Professor Marzyeh Ghassemi, who is a principal investigator at the Abdul Latif Jameel Clinic for Machine Learning in Health (Jameel Clinic), a member of the Computer Science and Artificial Intelligence Lab. Ghassemi, a faculty member in the MIT Department of Electrical Engineering and Computer Science and Institute for Medical Engineering and Science, runs the Healthy ML group, which focuses on robust machine learning in health.

Just how much information does a bad actor need to expose sensitive data, and what are the risks associated with the leaked information? To assess this, the research team developed a series of tests that they hope will lay the groundwork for future privacy evaluations. These tests are designed to measure various types of uncertainty, and assess their practical risk to patients by measuring various tiers of attack possibility.  

“We really tried to emphasize practicality here; if an attacker has to know the date and value of a dozen laboratory tests from your record in order to extract information, there is very little risk of harm. If I already have access to that level of protected source data, why would I need to attack a large foundation model for more?” says Ghassemi. 

With the inevitable digitization of medical records, data breaches have become more commonplace. In the past 24 months, the U.S. Department of Health and Human Services has recorded 747 data breaches of health information affecting more than 500 individuals, with the majority categorized as hacking/IT incidents.

Patients with unique conditions are especially vulnerable, given how easy it is to pick them out. “Even with de-identified data, it depends on what sort of information you leak about the individual,” Tonekaboni says. “Once you identify them, you know a lot more.”

In their structured tests, the researchers found that the more information the attacker has about a particular patient, the more likely the model is to leak information. They demonstrated how to distinguish model generalization cases from patient-level memorization, to properly assess privacy risk. 

The paper also emphasized that some leaks are more harmful than others. For instance, a model revealing a patient’s age or demographics could be characterized as a more benign leakage than the model revealing more sensitive information, like an HIV diagnosis or alcohol abuse. 

The researchers note that patients with unique conditions are especially vulnerable given how easy it is to pick them out, which may require higher levels of protection. “Even with de-identified data, it really depends on what sort of information you leak about the individual,” Tonekaboni says. The researchers plan to expand the work to become more interdisciplinary, adding clinicians and privacy experts as well as legal experts. 

“There’s a reason our health data is private,” Tonekaboni says. “There’s no reason for others to know about it.”

This work supported by the Eric and Wendy Schmidt Center at the Broad Institute of MIT and Harvard, Wallenberg AI, the Knut and Alice Wallenberg Foundation, the U.S. National Science Foundation (NSF), a Gordon and Betty Moore Foundation award, a Google Research Scholar award, and the AI2050 Program at Schmidt Sciences. Resources used in preparing this research were provided, in part, by the Province of Ontario, the Government of Canada through CIFAR, and companies sponsoring the Vector Institute.

de MIT News https://ift.tt/LzFYioq

New research may help scientists predict when a humid heat wave will break

A long stretch of humid heat followed by intense thunderstorms is a weather pattern historically seen mostly in and around the tropics. But climate change is making humid heat waves and extreme storms more common in traditionally temperate midlatitude regions such as the midwestern U.S., which has seen episodes of unusually high heat and humidity in recent summers.

Now, MIT scientists have identified a key condition in the atmosphere that determines how hot and humid a midlatitude region can get, and how intense related storms can become. The results may help climate scientists gauge a region’s risk for humid heat waves and extreme storms as the world continues to warm.

In a study appearing this week in the journal Science Advances, the MIT team reports that a region’s maximum humid heat and storm intensity are limited by the strength of an “atmospheric inversion”— a weather condition in which a layer of warm air settles over cooler air.

Inversions are known to act as an atmospheric blanket that traps pollutants at ground level. Now, the MIT researchers have found atmospheric inversions also trap and build up heat and moisture at the surface, particularly in midlatitude regions. The more persistent an inversion, the more heat and humidity a region can accumulate at the surface, which can lead to more oppressive, longer-lasting humid heat waves.

And, when an inversion eventually weakens, the accumulated heat energy is released as convection, which can whip up the hot and humid air into intense thunderstorms and heavy rainfall.

The team says this effect is especially relevant for midlatitude regions, where atmospheric inversions are common. In the U.S., regions to the east of the Rocky Mountains often experience inversions of this kind, with relatively warm air aloft sitting over cooler air near the surface.

As climate change further warms the atmosphere in general, the team suspects that inversions may become more persistent and harder to break. This could mean more frequent humid heat waves and more intense storms for places that are not accustomed to such extreme weather.

“Our analysis shows that the eastern and midwestern regions of U.S. and the eastern Asian regions may be new hotspots for humid heat in the future climate,” says study author Funing Li, a postdoc in MIT’s Department of Earth, Atmospheric and Planetary Sciences (EAPS).

“As the climate warms, theoretically the atmosphere will be able to hold more moisture,” adds co-author and EAPS Assistant Professor Talia Tamarin-Brodsky. “Which is why new regions in the midlatitudes could experience moist heat waves that will cause stress that they weren’t used to before.”

Air energetics

The atmosphere’s layers generally get colder with altitude. In these typical conditions, when a heat wave comes through a region, it warms the air at ground level. Since warm air is lighter than cold air, it will eventually rise, like a hot air balloon, prompting colder air to sink. This rise and fall of air sets off convection, like bubbles in boiling water. When warm air hits colder altitudes, it condenses into droplets that rain out, typically as a thunderstorm, that can often relieve a heat wave.

For their new study, Li and Tamarin-Brodsky wondered: What would it take to get air at the surface to convect and ultimately end a heat wave? Put another way: What sets the limit to how hot a region can get before air begins to convect to eventually rain?

The team treated the question as a problem of energy. Heat is energy that can be thought of in two forms: the energy that comes from dry heat (i.e., temperature), and the energy that comes from latent, or moist, heat. The scientists reasoned that, for a given portion or “parcel” of air, there is some amount of moisture that, when condensed, contributes to that air parcel’s total energy. Depending on how much energy an air parcel has, it could start to convect, rise up, and eventually rain out.

“Imagine putting a balloon around a parcel of air and asking, will it stay in the same place, will it go up, or will it sink?” Tamarin-Brodsky says. “It’s not just about warm air that’s lifting. You also have to think about the moisture that’s there. So we consider the energetics of an air parcel while taking into account the moisture in that air. Then we can find the maximum ‘moist energy’ that can accumulate near the surface before the air becomes unstable and convects.”

Heat barrier

As they worked through their analysis, the researchers found that the maximum amount of moist energy, or the highest level of heat and humidity that the air can hold, is set by the presence and strength of an atmospheric inversion. In cases where atmospheric layers are inverted (when a layer of warm or light air settles over colder or heavier, ground-level air), the air has to accumulate more heat and moisture in order for an air parcel to build up enough energy to lift up and break through the inversion layer. The more persistent the inversion is, the hotter and more humid air must get before it can rise up and convect.

Their analysis suggests that an atmospheric inversion can increase a region’s capacity to hold heat and humidity. How high this heat and humidity can get depends on how stable the inversion is. If a blanket of warm air parks over a region without moving, it allows more humid heat to build up, versus if the blanket is quickly removed. When the air eventually convects, the accumulated heat and moisture will generate stronger, more intense storms.

“This increasing inversion has two effects: more severe humid heat waves, and less frequent but more extreme convective storms,” Tamarin-Brodsky says.

Inversions in the atmosphere form in various ways. At night, the surface that warmed during the day cools by radiating heat to space, making the air in contact with it cooler and denser than the air above. This creates a shallow layer in which temperature increases with height, called a nocturnal inversion. Inversions can also form when a shallow layer of cool marine air moves inland from the ocean and slides beneath warmer air over the land, leaving cool air near the surface and warmer air above. In some cases, persistent inversions can form when air heated over sun-warmed mountains is carried over colder low-lying regions, so that a warm layer aloft caps cooler air near the ground.

“The Great Plains and the Midwest have had many inversions historically due to the Rocky Mountains,” Li says. “The mountains act as an efficient elevated heat source, and westerly winds carry this relatively warm air downstream into the central and midwestern U.S., where it can help create a persistent temperature inversion that caps colder air near the surface.”

“In a future climate for the Midwest, they may experience both more severe thunderstorms and more extreme humid heat waves,” Tamarin-Brodsky says. “Our theory gives an understanding of the limit for humid heat and severe convection for these communities that will be future heat wave and thunderstorm hotspots.”

This research is part of the MIT Climate Grand Challenge on Weather and Climate Extremes. Support was provided by Schmidt Sciences.

de MIT News https://ift.tt/hGnN3RD