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Why Do Dementia and Cognitive Decline Patients Remain Stuck in Past Memories?… KAIST Identifies Memory-Switching Mechanism
<(From Left) Professor Jin-Hee Han, Dr. Mujun Kim>
“Why do patients with dementia or cognitive decline remain stuck in past memories?”
KAIST researchers have identified, for the first time in the world, the existence of a “neural switch” in the brain that selectively retrieves the most recent memories. This study reveals the principle by which the brain selects necessary information between past memories and new memories, presenting new possibilities for future treatments for memory decline and reduced cognitive flexibility.
KAIST announced on the 17th of May that a research team led by Professor Jin-Hee Han of the Department of Biological Sciences has discovered, for the first time in the world, that a specific neural circuit connecting the medial septum (MS, a brain region that regulates memory and learning) and the medial entorhinal cortex (MEC, a brain region connected to the hippocampus* that processes memory information) switches between past and recent memories and plays a key role in selecting up-to-date information appropriate for the situation.
*Hippocampus: a key brain region that creates and stores new memories
We live by updating our memories through new experiences every day. For example, if the restaurant we visited today was more satisfying than the one we visited yesterday, the brain modifies the existing memory to reflect the new information. In this way, the ability to select necessary information between past and present memories is central to higher cognitive functions such as decision-making, problem-solving, future prediction, and logical reasoning. However, the principle by which the brain distinguishes and switches between memories has long remained unknown.
The research team focused on the medial septum, located deep within the brain. The medial septum regulates the activity rhythms of the hippocampus and acts as a “conductor” that helps the brain effectively store and retrieve information.
The study found that when specific neurons in the medial septum send signals to the medial entorhinal cortex, a brain region that processes memory information and delivers it to the hippocampus, the brain is better able to recall recent memories.
<(AI image) An inhibitory neural circuit switch in the MS–MEC pathway that regulates the selection between past and recent memories>
Conversely, when the research team artificially blocked this neural circuit using light, experimental animals were unable to use recent information and behaved according to past patterns. Neural activity in the hippocampus, which plays an important role in memory representation, also reverted to a past state. This shows that the circuit acts as a “neural switch” that selects the most recent information needed for the current situation among multiple memories.
The research team also analyzed memory performance according to brain activity states. Our brain repeatedly shifts between an “online state” (theta waves, brain waves activated during learning and concentration), in which it actively processes information, and an “offline state” (delta waves, slow brain waves that appear during sleep or rest), which is a resting state.
The analysis showed that the longer the online state was maintained, the better recent memories were recalled, while frequent switching between online and offline states significantly reduced memory retrieval ability. This suggests that specific brain rhythms and states are important neurobiological indicators that determine effective memory retrieval.
This study is significant in that it identified the mechanism by which the brain flexibly reflects new information while maintaining past memories. The research team expects that this discovery could lead to the development of new therapeutic technologies to improve memory decline and reduced cognitive flexibility in patients with degenerative brain diseases such as dementia and Alzheimer’s disease.
<An inhibitory neural circuit switch in the MS–MEC pathway that regulates the selection between past and recent memories>
Professor Jin-Hee Han stated, “This study presents a new paradigm for understanding the principle by which our brain organizes and uses numerous experiences in chronological order,” adding, “Previously, memory retrieval was understood simply as the replaying of stored traces, but through this study, we proved that the brain has a regulatory system that actively selects recent information among competing memories.”
This study involved Dr. Mujun Kim of the Department of Biological Sciences at KAIST, doctoral students Boin Suh, Sunhoi So, Jung Wook Choi, Jaemin Hwang, and Juhee Park, and was published on April 29 in Nature Neuroscience, a top-tier international journal in neuroscience.
※ Paper title: “A septo-entorhinal GABAergic pathway that enables switching between episodic memories,” https://doi.org/10.1038/s41593-026-02280-6 ※ Author information: Mujun Kim (KAIST, first author), Boin Suh (KAIST), Sunhoi So (KAIST), Jung Wook Choi (KAIST), Jaemin Hwang (KAIST), Juhee Park (KAIST) & Jin-Hee Han (KAIST, corresponding author)
This research was supported by the Mid-Career Research Program (National Research Foundation of Korea), the Samsung Science and Technology Foundation, and the KAIST Jang Young Sil Fellow Program.
2026.05.18 View 198 -
3D Stem Cell Culture Technology to Shift the Paradigm of Regenerative Medicine
< (From left) KAIST Dr. Changjin Seo, Professor Sangyong Jon >
A breakthrough technology has been developed to overcome the limitation where stem cells fail to survive for long periods in the body, even when administered in large quantities. Stem cells are vital for regenerating damaged tissues or recovering injured areas. A KAIST research team has successfully enhanced both the survival rate and therapeutic efficacy of these cells by developing a 3D culture technology that precisely designs the cellular microenvironment. This achievement is expected to transcend the current limits of stem cell therapy and reshape the landscape of regenerative medicine.
On April 29th, the research team—led by Professor Sangyong Jon from the Department of Biological Sciences and featuring researchers Changjin Seo, Dohyeon Kim, Junhyuk Song, Sun-Young Kim, Youngju Son, and Afia Tasnim Rahman—announced the development of a novel culture technology to grow healthier stem cells. The team implemented a 3D platform by applying a polymer matrix (an artificial structure coating the culture substrate) to an "artificial floor" that mimics the natural in vivo environment. On this platform, they cultured human adipose-derived stem cells (hADSCs) in three dimensions, confirming a dramatic improvement in cellular function and therapeutic impact.
Human adipose-derived stem cells have been favored for clinical use due to their ease of harvest, high proliferation, and low immune rejection. However, traditional 2D (planar) culture methods cause cells to age and lose function over time. Previous 3D methods, such as forming cell aggregates (spheroids), also faced hurdles in maintaining long-term survival and functionality within the body.
To solve this, the research team developed a densely cross-linked synthetic polymer material composed of siloxane (a biocompatible polymer of silicon and oxygen), named "poly-Z."
This material modifies the physicochemical properties of the culture substrate to promote the adsorption of albumin proteins found in the culture medium. As a result, cells do not adhere to the floor but instead self-assemble into 3D spheroid structures. These spheroids showed increased production of the extracellular matrix (ECM), creating an environment highly similar to the human body and demonstrating performance far superior to conventional methods.
Experimental results showed that stem cells cultured on the poly-Z platform exhibited enhanced differentiation potential and immunomodulatory functions, with a significantly increased survival time inside the body.
< Schematic of hADSC Spheroid Formation on the Synthetic Polymer Matrix, Poly-Z >
Notably, in animal models of acute colitis and acute liver injury, this method showed significantly higher therapeutic efficacy than conventional methods. This suggests that even with the same dosage, the cells live longer and act more vigorously. The team confirmed that the activation of integrin and FAK signaling pathways—the mechanisms through which cells sense and respond to their environment—strengthened the stem cells' functions, allowing them to better perceive their surroundings and perform more effectively after transplantation.
Professor Sangyong Jon stated, "This research proves that a precisely engineered synthetic polymer-based 3D environment can simultaneously enhance the function and therapeutic efficacy of stem cells. We expect this to be widely utilized in developing next-generation cell therapies for various incurable diseases, including inflammatory conditions."
The study, with Dr. Changjin Seo from the KAIST InnoCORE AI-Drug Discovery Center as the lead author, was published online on March 31 in the international journal Advanced Science (Impact Factor: 14.1).
Paper Title: Polymer Matrix-Based 3D Culture Significantly Enhances the Differentiation and Immunomodulatory Functions of Human Adipose-Derived Stem Cells
DOI: https://doi.org/10.1002/advs.202518704
This research was supported by the Korea Multi-Ministry Regenerative Medicine Project, the KAIST InnoCORE Program, and the Leader Research Grant of the National Research Foundation of Korea.
2026.04.29 View 317 -
Discovery of the Two-Faced Protein in Leukemia Treatment: A Clue to Overcoming Drug Resistance
<(From left) Professor Dong-Wook Kim of Uijeongbu Eulji University Hospital Hematologic Malignancy Center, Professor Hongtae Kim of UNIST, Professor Chunghun Lim of KAIST, and Dr. Jumin Park of KAIST>
The real reason why anticancer drugs kill cancer cells has been revealed. KAIST research team has identified that targeted anticancer therapies do not simply block cancer proteins, but rather shut down the "protein factories" inside the cells, forcing them to undergo self-destruction. Consequently, the "two-faced protein" that plays a key role in this process is gaining attention as a breakthrough for treating patients with drug resistance.
KAIST announced on April 23rd that a joint research team—consisting of Professor Chunghun Lim from the Department of Biological Sciences at KAIST, Professor Dong-Wook Kim from the Hematologic Malignancy Center at Uijeongbu Eulji University Hospital, and Professor Hongtae Kim from UNIST —has identified a new molecular mechanism that regulates the response to anticancer drugs for Chronic Myeloid Leukemia (CML).
Chronic Myeloid Leukemia occurs when genetic abnormalities in hematopoietic stem cells produce an abnormal protein. This protein is known to be the primary cause of cancer cell proliferation by sending continuous growth signals to the cells. While targeted anticancer drugs that inhibit this protein are currently used as the standard treatment, there have been limitations, such as drug resistance or low treatment response in some patients.
The research team focused on the impact of anticancer drugs on the protein production process within the cell. As a result, they confirmed that when anticancer drugs are administered, the flow of ribosomes—the machines that create proteins—becomes tangled, leading to "ribosome collisions." This process induces intense stress inside the cell, ultimately leading the cancer cell to its death.
In particular, the research team identified the ZAK protein as the key sensor that detects these ribosome collisions and discovered that ZAK possesses "two faces" depending on the situation. Under normal conditions, it acts as an assistant, binding with AKT signals* to help cancer cells grow. However, once targeted anticancer treatment begins, it transforms into a sentinel that monitors ribosome collisions and triggers the death of the cancer cell. This marks the world's first proof that the same protein can perform diametrically opposite roles during cancer progression versus cancer treatment. *A key intracellular signaling pathway that regulates cell survival, growth, proliferation, metabolism, and migration.
<Clinical correlation between disease stage and ZAK expression in a Chronic Myeloid Leukemia patient cohort>
The research team verified this mechanism by analyzing cancer cells derived from actual leukemia patients. When drugs that increase ribosome collisions were used in combination, the anticancer effect improved significantly. Conversely, when ZAK function was impaired, the responsiveness to the anticancer drug decreased.
<Mechanism of ribosome collision and ZAK-dependent cancer cell death induced by Targeted Kinase Inhibitors (TKIs) in Chronic Myeloid Leukemia>
In other words, according to this study, drug-resistant patients are predicted to have decreased ZAK function or an insufficient ribosome stress response. This suggests that it is possible to predict treatment responses based on an individual patient's ZAK activation status and design customized combination therapy strategies.
This study is a significant achievement that presents the importance of the ribosome stress signaling pathway in the treatment of Chronic Myeloid Leukemia. It is expected to lead to the development of new combination therapies and enhance the effectiveness of targeted anticancer drugs. In particular, it offers new possibilities for patients struggling with drug resistance.
<Research Image (AI-generated)>
Professor Chunghun Lim stated, "This study shows how critical the process of the cell detecting abnormal protein synthesis and converting it into a death signal is for treatment." Dr. Jumin Park, the lead author, noted, "As we have confirmed that ribosome collision is a key switch determining cancer cell death, we plan to expand this research to various other types of cancer."
The results of this study, featuring Jumin Park of KAIST as the first author, were published online on March 30th in Leukemia, one of the most prestigious academic journals in the field of hematology.
Paper Title: BCR::ABL1 tyrosine kinase inhibitors induce ribosome collisions to activate ZAK-dependent ribotoxic stress and apoptosis in chronic myeloid leukemia
Authors: Jumin Park, Soo-Hyun Kim, Jongmin Park, Heeju Park, Hongtae Kim, Dong-Wook Kim & Chunghun Lim
DOI: https://doi.org/10.1038/s41375-026-02916-3
This research was conducted with support from the Suh Kyungbae Foundation, the Mid-career Researcher Support Program of the National Research Foundation of Korea, the Basic Research Lab Support Program, and the KAIST Settlement Project.
2026.04.23 View 423 -
Era of Ultra-Slim, Wide Field-of-View and , High-Resolution Cameras Opens with Natural Vision Principles
<(From left) Young-Gil Cha, Hyun-Kyung Kim, Jae-Myeong Kwon, Professor Ki-Hun Jeong, (Top right) Professor Min H. Kim>
A breakthrough technology has emerged to fundamentally solve the "camera protrusion/thickness issue," which has been a persistent limitation as smart devices become thinner. KAIST research team has developed an ultra-thin camera that achieves a wide 140-degree field of view (FOV) without any lens protrusion. This technology is expected to be applied across various fields, including medical endoscopes, wearable devices, and micro-robots.
On the 7th, a joint research team led by Professor Ki-Hun Jeong from the Department of Bio and Brain Engineering and Professor Min H. Kim from the School of Computing announced the development of a "wide-angle biomimetic camera." Inspired by insect vision, the camera is exceptionally thin yet boasts a vast field of view. The team successfully secured a diagonal FOV of 140 degrees—surpassing human peripheral vision—within an ultra-thin structure of less than 1 mm, roughly the thickness of a coin.
High-performance wide-angle cameras typically require multiple stacked lenses, inevitably leading to increased thickness. To overcome this, the research team focused on the visual structure of the parasitic insect Xenos peckii.
<Conceptual diagram of the camera structure mimicking insect compound eye principles and photos of the manufactured ultra-thin camera>
While typical insect compound eyes offer a wide FOV, they suffer from low resolution. Conversely, single-lens cameras provide high resolution but limited FOV. Xenos peckii, however, possesses a unique visual system where multiple eyes capture partial segments of a scene, which the brain then integrates into a single high-resolution image. By introducing this "split-capture and integration" principle into the camera architecture, the team simultaneously achieved both thinness and high image quality. This overcomes the low-resolution issues of conventional compound eye cameras and the narrow FOV limits of single-lens systems.
<Result of reconstructing a single scene by combining partial images captured via a microlens array>
The team implemented a method where several micro-lenses with ellipsoidal shape capture different directions simultaneously, merging them into one sharp image without optical aberration. Notably, by precisely adjusting the lens shape and light entry points, they prevented blurring at the edges of the frame. As a result, uniform clarity is maintained from the center to the periphery, enabling stable imaging even at very close ranges.
With a thickness of only 0.94 mm, this ultra-thin camera is expected to bring innovation to space-constrained fields. It can significantly enhance image acquisition efficiency for medical endoscopes requiring precise observation of narrow areas, as well as for micro-robots and wearable healthcare equipment. This technology shifts the design paradigm from increasing device size for better performance to enabling high-performance imaging in ultra-small form factors.
<Results of photographing actual subjects at close range: microfluidic channels (20 mm distance), oral models (30 mm), and human faces (50 mm)>
Furthermore, the research team has completed a technology transfer to MicroPix Co., Ltd., a specialist in optical imaging, with the goal of full-scale commercialization by next year.
"Conventional wide-angle cameras faced a trade-off where reducing size lowered resolution, and increasing resolution enlarged the device," explained Professor Ki-Hun Jeong. "By applying visual principles from nature, we have secured both a wide FOV and stable image quality in an ultra-compact structure. This is a new image acquisition method usable even in extreme space-constrained environments."
Jae-Myeong Kwon, Ph.D candidate at KAIST, participated as the lead author. The study was published on March 23 in the world-renowned academic journal Nature Communications.
Paper Title: Biologically inspired microlens array camera for high-resolution wide field-of-view imaging
DOI: https://doi.org/10.1038/s41467-026-70967-2
Authors: Jae-Myeong Kwon, Yejoon Kwon, Young-Gil Cha, Dong Hyun Han, Hyun-Kyung Kim, Je-Kyun Park, Min H. Kim & Ki-Hun Jeong
This research was conducted with support from the Mid-Career Researcher Program of the National Research Foundation of Korea (Ministry of Science and ICT), the Korean ARPA-H Project (Ministry of Health and Welfare), and the Materials and Components Technology Development Program (Ministry of Trade, Industry and Energy).
2026.04.07 View 757 -
KAIST, Flowers Have a “Biological Clock” That Times Blooming and Scent to Match Insects
Morning-blooming morning glories and flowers that release fragrance at night seem as if they know the time. A KAIST research team has uncovered, at the molecular level, the principle by which plants precisely control the timing of flower opening and scent emission through a “biological clock” aligned with insect behavior. This study suggests potential applications in technologies for controlling flowering time and fragrance.
KAIST (President Kwang Hyung Lee) announced on the 27th of March that a research team led by Professor Sang-Gyu Kim of the Department of Biological Sciences has discovered that genes regulated by the plant biological clock integratively control both the timing of flower opening and the circadian rhythm of scent emission.
Plants are known to have physiological processes regulated by a “biological clock” that allows them to perceive time according to a daily cycle. However, the exact process by which flowers open and how this process is connected to biological clock genes has not yet been fully elucidated.
The research team conducted their study using Nicotiana attenuata (coyote tobacco), a plant that opens its flowers widely at night and emits fragrance. Native to desert regions of Utah, USA, this plant is characterized by opening its flowers and releasing scent at night to attract nocturnal pollinators.
Inspired by such phenomena, the biologist Linnaeus proposed the idea of a “flower clock,” suggesting that if plants that bloom and close at different times were gathered together, one could tell the time based solely on their flowering states.
Previous studies mainly focused on analyzing changes in gene expression related to flower development, but research directly identifying the phenomenon of flower opening and the genes controlling it has been limited. To overcome these limitations, the research team analyzed mutants with altered biological clock genes and investigated, through molecular biological approaches, how flower opening and scent emission are regulated.
< A comparison of wild-type plants and COL5 (a specific circadian clock gene) mutant plants >
As a result, the team confirmed that specific biological clock genes play a key role in controlling both the timing of flower opening and the rhythm of scent emission. This demonstrates that plants make precise use of their biological clock to open flowers and attract pollinators at the most advantageous times for survival and reproduction.
< AI-generated image (the rhythmic behavior of coyote tobacco flowers regulated by the COL5 gene) >
This study is meaningful in that it presents a gene regulatory network controlling flower opening and scent emission from the perspective of the biological clock. It is also expected to provide important clues for understanding plants’ time-regulation strategies and their ecological interactions.
Professor Sang-Gyu Kim stated, “This study provides insight into how the plant biological clock links and regulates the timing of flower opening and scent emission,” adding, “It is expected to serve as an important foundation for understanding how plants optimize their reproductive strategies through interactions with the environment.”
This research, with Dr. Yuri Choi and Dr. Moonyoung Kang from the Department of Biological Sciences as co-first authors, was published on January 29 in the international journal The Plant Cell.
※ Paper title: ”CONSTANS-LIKE 5 facilitates flower opening and scent biosynthesis in Solanaceae” https://doi.org/10.1093/plcell/koag016
This research was supported by the National Research Foundation of Korea’s Synthetic Biology Core Technology Development Program, the Mid-career Researcher Program, and the Rural Development Administration’s Next-Generation Crop Breeding Technology Development Program.
2026.03.27 View 592 -
KAIST Develops mRNA Platform That Remains Effective Even in Aging and Obesity
<(From Left) Dr. Subin Yoon, Ph.D candidate Hyeonggon Cho, Prof. Jae-Hwan Nam, Prof. Young-suk Lee>
Since the COVID-19 pandemic, mRNA vaccines have gained attention as a next-generation pharmaceutical technology. mRNA therapeutics work by delivering genetic instructions that enable cells to produce specific proteins for therapeutic effects. However, their efficacy has been reported to decline in elderly individuals or patients with obesity. To address this limitation, Korean researchers have newly designed a key regulatory region of mRNA that improves therapeutic protein production efficiency, developing a next-generation mRNA platform that maintains effectiveness even in aging and obesity conditions.
KAIST (President Kwang Hyung Lee) announced on the 10th of March that a joint research team led by Professor Young-suk Lee of the Department of Bio and Brain Engineering and Professor Jae-Hwan Nam of The Catholic University of Korea (President Jun-Gyu Choi) has developed a new mRNA platform by precisely designing the sequence of the 5′ untranslated region (5′UTR)*, a key regulatory region of mRNA.*5′ untranslated region (5′UTR): A region of mRNA that initiates and regulates protein production. The design of this region influences both the amount and speed of protein synthesis.
The research team analyzed large-scale bioinformatics datasets to identify 5′UTR sequences that enable proteins to be produced more efficiently across diverse cellular environments. When applied, the designed sequences significantly enhanced protein production and immune responses even in preclinical models of aging and obesity.
mRNA is a long single-stranded RNA molecule that serves as the blueprint for producing proteins required by the body. It consists of several components: the 5′UTR, which initiates and regulates the rate of protein production; the coding sequence (CDS), which contains the genetic information for a specific protein; the 3′ untranslated region (3′UTR), which helps maintain mRNA stability within cells; and the poly(A) tail, which further enhances stability and supports protein synthesis.
Among these components, the 5′UTR and 3′UTR do not determine the type of protein produced, but they play a critical role in regulating how efficiently the protein is synthesized. For this reason, these regions are receiving increasing attention as key bioengineering platforms for improving the performance of various mRNA therapeutics, including vaccines and treatments.
<Schematic Diagram of mRNA Therapeutic Design and Validation Using Bioinformatics>
To identify highly efficient 5′UTR sequences capable of promoting protein production across multiple tissues and cellular environments, the team conducted an integrated analysis of large-scale biological datasets. This included multiple analytical approaches such as RNA sequencing (RNA-seq) for analyzing gene activity across tissues, single-cell RNA sequencing (scRNA-seq) for examining gene expression at the individual cell level, and ribosome profiling (Ribo-seq) for measuring actual protein translation efficiency.
The researchers also focused on the fact that in aging or obesity conditions, cells often experience high levels of stress—particularly oxidative stress—which can reduce their ability to synthesize proteins. When the newly designed mRNA therapeutics were applied to preclinical models of aging and obesity, the results showed significantly improved protein production and immune responses compared with existing approaches. This research is expected to be applicable not only to mRNA vaccines but also to a wide range of biopharmaceutical technologies, including gene therapies and immunotherapies.
<Multimodal Bio–Big Data Analysis–Based mRNA Therapeutic Design (AI-Generated Image)>
Professor Young-suk Lee of KAIST Department of Bio and Brain Engineering stated, “This study identified a design strategy that enables mRNA to produce proteins more efficiently by analyzing large-scale biological data,” adding, “This technology will provide an important foundation for ensuring that mRNA vaccines and therapeutics remain effective even in environments where drug efficacy may decline, such as in elderly or obese patients.”
In this study, Dr. Subin Yoon from The Catholic University of Korea and doctoral candidate Hyeonggon Cho from KAIST participated as co-first authors. The research findings were published online on January 2 in the internationally renowned journal Molecular Therapy (IF = 12.0), a leading journal in gene and cell therapy.
(Paper title: ”Designing 5′UTR sequences improves the capacity of mRNA therapeutics in preclinical models of aging and obesity” DOI: https://doi.org/10.1016/j.ymthe.2025.12.060)
This research was supported by the Excellent Young Researcher Program and the Bio-Medical Technology Development Program of the National Research Foundation of Korea funded by the Ministry of Science and ICT, the Infectious Disease Response Innovative Technology Support Program of the Ministry of Food and Drug Safety, and the Infectious Disease Prevention and Therapeutics Technology Development Program of the Korea Health Industry Development Institute.
2026.03.10 View 1413 -
KAIST Awakens dormant immune cells inside tumors to attack cancer
<(From Left) Professor Ji-Ho Park, Dr. Jun-Hee Han from the Department of Bio and Brain Engineering>
Within tumors in the human body, there are immune cells (macrophages) capable of fighting cancer, but they have been unable to perform their roles properly due to suppression by the tumor. KAIST researchers have overcome this limitation by developing a new therapeutic approach that directly converts immune cells inside tumors into anticancer cell therapies.
KAIST (President Kwang Hyung Lee) announced on the 30th that a research team led by Professor Ji-Ho Park of the Department of Bio and Brain Engineering has developed a therapy in which, when a drug is injected directly into a tumor, macrophages already present in the body absorb it, produce CAR (a cancer-recognizing device) proteins on their own, and are converted into anticancer immune cells known as “CAR-macrophages.”
Solid tumors—such as gastric, lung, and liver cancers—grow as dense masses, making it difficult for immune cells to infiltrate tumors or maintain their function. As a result, the effectiveness of existing immune cell therapies has been limited.
CAR-macrophages, which have recently attracted attention as a next-generation immunotherapy, have the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to amplify anticancer responses.
However, conventional CAR-macrophage therapies require immune cells to be extracted from a patient’s blood, followed by cell culture and genetic modification. This process is time-consuming, costly, and has limited feasibility for real-world patient applications.
To address this challenge, the research team focused on “tumor-associated macrophages” that are already accumulated around tumors.
They developed a strategy to directly reprogram immune cells in the body by loading lipid nanoparticles—designed to be readily absorbed by macrophages—with both mRNA encoding cancer-recognition information and an immunostimulant that activates immune responses.
In other words, in this study, CAR-macrophages were created by “directly converting the body’s own macrophages into anticancer cell therapies inside the body.”
<Figure . Schematic illustration of the strategy for in vivo CAR-macrophage generation and cancer cell eradication via co-delivery of CAR mRNA and immunostimulants using lipid nanoparticles (LNPs)>
When this therapeutic agent was injected into tumors, macrophages rapidly absorbed it and began producing proteins that recognize cancer cells, while immune signaling was simultaneously activated. As a result, the generated “enhanced CAR-macrophages” showed markedly improved cancer cell–killing ability and activated surrounding immune cells, producing a powerful anticancer effect.
In animal models of melanoma (the most dangerous form of skin cancer), tumor growth was significantly suppressed, and the therapeutic effect was shown to have the potential to extend beyond the local tumor site to induce systemic immune responses.
Professor Ji-Ho Park stated, “This study presents a new concept of immune cell therapy that generates anticancer immune cells directly inside the patient’s body,” adding that “it is particularly meaningful in that it simultaneously overcomes the key limitations of existing CAR-macrophage therapies—delivery efficiency and the immunosuppressive tumor environment.”
This research was led by Jun-Hee Han, Ph.D., of the Department of Bio and Brain Engineering at KAIST as the first author, and the results were published on November 18 in ACS Nano, an international journal in the field of nanotechnology.
※ Paper title: “In Situ Chimeric Antigen Receptor Macrophage Therapy via Co-Delivery of mRNA and Immunostimulant,” Authors: Jun-Hee Han (first author), Erinn Fagan, Kyunghwan Yeom, Ji-Ho Park (corresponding author), DOI: 10.1021/acsnano.5c09138
This research was supported by the Mid-Career Researcher Program of the National Research Foundation of Korea.
2025.12.31 View 3679 -
AI-Engineered "Nasal Spray Antiviral Platform" Developed to Block Flu and COVID-19
<(From Left) Professor Hyun Jung Chung, Professor Ho Min Kim, Professor Ji Eun Oh>
<(From Left) Dr. Seungju Yang, Dr. Jeongwon Yun, Ph.D candidate Jae Hyuk Kwon>
Respiratory viruses that have diverse strains and mutate rapidly, such as influenza and COVID-19, are difficult to block perfectly with vaccines alone. To solve this problem, KAIST's research team has successfully developed a nasal (intranasal) antiviral platform using AI technology to overcome the existing limitations of interferon-lambda treatments—namely, being "weak against heat and disappearing quickly from the nasal mucosa."
KAIST announced on December 15th that a joint research team—consisting of Professor Ho Min Ktim and Professor Hyun Jung Chung from the Department of Biological Sciences, and Professor Ji Eun Oh from the Graduate School of Medical Science and Engineering used AI to stably redesign the interferon-lambda protein and combined it with a delivery technology that ensures effective diffusion and long-term retention in the nasal mucosa, thereby implementing a universal prevention technology for various respiratory viruses.
Interferon-lambda is an innate immune protein produced by the body to block viral infections, playing a crucial role in stopping respiratory viruses like the common cold, flu, and COVID-19. However, when formulated as a treatment for nasal administration, its actual efficacy was limited by its vulnerability to heat, degrading enzymes, mucus, and ciliary motion.
The research team used AI protein design technology to precisely reinforce the structural weaknesses of interferon-lambda.
First, they significantly increased stability by changing the loose "loop" structures of the protein—which were prone to instability—into rigid "helix" structures that lock in place like a firm spring.
Additionally, to prevent "aggregation" (proteins sticking together to form lumps), they applied "surface engineering" to make the surface more water-compatible. They also introduced "glycoengineering," adding sugar chain (glycan) structures to the protein surface to make it even more robust and stable.
As a result, the newly produced interferon-lambda showed a massive improvement in stability, surviving for two weeks 50℃ and demonstrated the ability to diffuse rapidly even through thick nasal mucus.
The research team further protected the protein by encapsulating it in microscopic "nanoliposomes" and coated the surface with "low-molecular-weight chitosan." This significantly enhanced "mucoadhesion," allowing the treatment to stick to the nasal lining for an extended period.
When this delivery platform was applied to animal models infected with influenza, a powerful inhibitory effect was confirmed, with the virus level in the nasal cavity decreasing by more than 85%.
This technology is a mucosal immune platform that can block viral infections in their early stages simply by spraying it into the nose. It is expected to be a new therapeutic strategy that can respond quickly not only to seasonal flu but also to unexpected new or mutant viruses.
Professor Ho Min Kim stated, "Through AI-based protein design and mucosal delivery technology, we have simultaneously overcome the stability and retention time limitations of existing interferon-lambda treatments. This platform, which is stable at high temperatures and stays in the mucosa for a long time, is an innovative technology that can be used even in developing countries lacking strict cold-chain infrastructure. It also has great scalability for developing various treatments and vaccines." He added, "This is a meaningful achievement resulting from multidisciplinary convergence research, covering everything from AI protein design to drug delivery optimization and immune evaluation through infection models."
This research involved Dr. Jeongwon Yun from the KAIST InnoCORE (AI-Co-Research & Eudcation for innovative Drug Institute, AI-CRED Institute) Dr. Seungju Yang from the Department of Biological Sciences, and PhD student Jae Hyuk Kwon from the Graduate School of Medical Science and Engineering as co-first authors. The results were published consecutively in the renowned international journals Advanced Science (Nov 20) and Biomaterials Research (Nov 21).
Paper 1: Computational Design and Glycoengineering of Interferon-Lambda for Nasal Prophylaxis against Respiratory Viruses, Advanced Science, DOI: 10.1002/advs.202506764
Paper 2: Intranasal Nanoliposomes Delivering Interferon Lambda with Enhanced Mucosal Retention as an Antiviral, Biomaterials Research, DOI: 10.34133/bmr.0287
This research was conducted with support from the KAIST InnoCORE Program, Mid-Career Researcher Support Program and the Bio-Medical Technology Development Program through the National Research Foundation of Korea (NRF), Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), the KAIST Convergence Research Institute Operation Program, and the Institute for Basic Science (IBS).
2025.12.15 View 2400 -
KAIST Discovers Role of Huntingtin Protein in Building the Cell Skeleton
<(From Left) Professor Ji-Joon Song, Ph.D candidate Jaesung Kim, Dr. Hyeongju Kim of KAIST’s Department of Biological Sciences>
Huntington’s disease is a rare genetic disorder and a representative neurodegenerative disease, characterized by loss of motor control, cognitive decline, and psychiatric problems. An international research team has discovered that the “huntingtin protein,” the causal protein of Huntington’s disease (whose mutations are the direct cause of the disease), also performs a new function: directly organizing the cytoskeleton, the fine structural framework inside cells. This discovery is expected to contribute not only to understanding the pathogenic mechanism of Huntington’s disease, but also to research on neurodevelopmental disorders such as Alzheimer’s disease and Parkinson’s disease, as well as muscle- or mobility-related diseases such as muscular dystrophy.
KAIST (President Kwang Hyung Lee) announced on September 30 that a research team led by Professor Ji-Joon Song of the Department of Biological Sciences, in collaboration with the Institute of Science and Technology Austria (ISTA), Sorbonne University/Paris Brain Institute, and the Swiss Federal Institute of Technology Lausanne (EPFL), has uncovered—through cryo-electron microscopy (cryo-EM) and cell biology methods—the structural principle by which the huntingtin protein arranges cytoskeletal microfilaments (F-actin) into bundles.
Until now, the huntingtin protein was known only to “use” the cytoskeleton, being involved in vesicle transport or microtubule-based transport. The team, however, demonstrated that huntingtin physically organizes the cytoskeleton itself. This study is considered the first in the world to prove this new role of the huntingtin protein at the molecular level.
The researchers confirmed that huntingtin binds directly to cytoskeletal microfilaments (F-actin), and that pairs of huntingtin proteins bundle the cytoskeleton into arrays at intervals of about 20 nanometers.
Such cytoskeletal bundles play a crucial role in the development of neural connectivity. Indeed, structural development of neurons was found to be impaired in nerve cells deficient in the huntingtin protein.
<Elucidation of the Mechanism of Cytoskeletal Microfilament Bundle Formation by Huntingtin Protein and Its Impact on Neuronal Development>
First author Jaesung Kim, a PhD candidate at KAIST, stated, “This study provides a new perspective for understanding the molecular mechanism of the huntingtin protein, the cause of an incurable disease that has long remained a mystery.”
Professor Ji-Joon Song of KAIST’s Department of Biological Sciences explained, “This achievement not only provides an important clue to understanding the pathogenic mechanism of Huntington’s disease, but is also expected to have a far-reaching impact on research into cytoskeleton-related diseases,” and added that “it opens new avenues for exploring the role of the huntingtin protein in diverse biological phenomena such as cell division, migration, and mechanical signal transduction.”
This research was conducted with Jaesung Kim (PhD candidate, KAIST), Hyeongju Kim (now at Harvard University), Rémi Carpentier (Paris Brain Institute), Mariacristina Capizzi (Paris Brain Institute), and others as co-first authors, and was published on September 19 in Science Advances, a sister journal of Science.
※ Paper title: “Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization,” DOI: https://doi.org/10.1126/sciadv.adw4124※ Co-corresponding authors: Ji-Joon Song (KAIST), Florian Schur (ISTA), and Sandrine Humbert (Sorbonne University/Paris Brain Institute).
This research was supported by the Ministry of Health and Welfare’s Global Research Collaboration Program (Korea–Switzerland Biohealth International Joint Research) and the Korea–Austria Cooperation Program.
2025.09.30 View 3107 -
Thinking outside the box to Fabricate Customized 3D Neural Chips
<(From Left) Professor Yoonkey Nam, Dr. Dongjo Yoon from the Department of Bio and Brain Engineering>
Cultured neural tissues have been widely used as a simplified experimental model for brain research. However, existing devices for growing and recording neural tissues, which are manufactured using semiconductor processes, have limitations in terms of shape modification and the implementation of three-dimensional (3D) structures.
By "thinking outside the box," a KAIST research team has successfully created a customized 3D neural chip. They first used a 3D printer to fabricate a hollow channel structure, then used capillary action to automatically fill the channels with conductive ink, creating the electrodes and wiring. This achievement is expected to significantly increase the design freedom and versatility of brain science and brain engineering research platforms.
On the 25th, KAIST announced that a research team led by Professor Yoonkey Nam from the Department of Bio and Brain Engineering has successfully developed a platform technology that overcomes the limitations of traditional semiconductor-based manufacturing. This technology allows for the precise fabrication of "3D microelectrode array" (neural interfaces with multiple microelectrodes arranged in a 3D space to measure and stimulate the electrophysiological signal of neurons) in various customized forms for in vitro culture chips.
Existing 3D microelectrode array fabrication, based on semiconductor processes, has limited 3D design freedom and is expensive. While 3D printing-based fabrication techniques have recently been proposed to overcome these issues, they still have limitations in terms of 3D design freedom for various in vitro neural network structures because they follow the traditional sequence of "conductive material patterning → insulator coating → electrode opening."
The KAIST research team leveraged the excellent 3D design freedom provided by 3D printing technology and its ability to use printed materials as insulators. By reversing the traditional process, they established an innovative method that allows for more flexible design and functional measurement of 3D neuronal network models for in vitro culture.
<Schematic Diagram of an Integrated Cell Culture Substrate-Microelectrode Array Platform for In Vitro Cultured 3D Neural Network Models>
First, they used a 3D printer to print a hollow 3D insulator with micro-tunnels. This structure was designed to serve as a stable scaffold for conductive materials in 3D space while also supporting the creation of various 3D neuronal networks. They then demonstrated that by using capillary action to fill these internal micro-tunnels with conductive ink, they could create a 3D scaffold-microelectrode array with more freely arranged microelectrodes within a complex 3D culture support structure.
The new platform can be used to create various chip shapes, such as probe-type, cube-type, and modular-type, and supports the fabrication of electrodes using different materials like graphite, conductive polymers, and silver nanoparticles. This allows for the simultaneous measurement of multichannel neural signals from both inside and outside the 3D neuronal network, enabling precise analysis of the dynamic interactions and connectivity between neurons.
Professor Nam stated, "This research, which combines 3D printing and capillary action, is an achievement that significantly expands the freedom of neural chip fabrication." He added that it will contribute to the advancement of fundamental brain science research using neural tissue, as well as applied fields like cell-based biosensors and biocomputing.
Dr. Dongjo Yoon from KAIST's Department of Bio and Brain Engineering participated as the first author of the study. The research findings were published online in the international academic journal Advanced Functional Materials (June 25th issue).
※Paper Title: Highly Customizable Scaffold-Type 3D Microelectrode Array Platform for Design and Analysis of the 3D Neuronal Network In Vitro
This research was supported by the Consolidator Grants Program and the Global Basic Research Laboratory Program of the National Research Foundation of Korea.
2025.09.26 View 2720 -
KAIST team links early life epigenetic memory to adult brain inflammation
<(From left) Professor Won-Suk Chung, Ph.D. Ph.D candidate Hyeonji Park Dr. Seongwan Park, Professor Inkyung Jung>
Why do some people remain healthy through childhood yet become more vulnerable to brain disorders such as dementia later in life? A KAIST (President Kwang Hyung Lee) -led team has uncovered a key part of the answer: a developmental ‘switch’ in astrocytes—the brain’s most abundant support cells that shapes how strongly the brain’s immune system reacts in adulthood. The study identifies a gene, NR3C1 (encoding the glucocorticoid receptor), as a master regulator of this switch and shows how early-life epigenetic ‘memory’ can predispose the adult brain to excessive inflammation.
The work was carried out by a joint team led by Professor Inkyung Jung (Department of Biological Sciences, KAIST) and Associate Director Won-Suk Chung (Center for Vascular Research, Institute for Basic Science; Professor, KAIST Biological Sciences). Using mouse models, the researchers mapped gene-regulatory programs across multiple stages of astrocyte development and found that NR3C1 acts during a brief early-postnatal window to enforce long-term immune restraint.
<The schematic illustrates how the NR3C1 gene (glucocorticoid receptor) suppresses the immune response of astrocytes. In normal (control) astrocytes, NR3C1 binds to specific regulatory regions of DNA (nGRE) to inhibit the expression of immune-related genes, thereby maintaining brain homeostasis even under immune stimulation. In contrast, in NR3C1-deficient astrocytes (KO), this suppression is lost, leading to excessive activation of inflammation-related genes such as Gfap, Il6st, Stat2, and Cxcl10. As a result, in an autoimmune encephalomyelitis (EAE) model, pronounced neuroinflammation and clinical symptoms (paralysis and severe debilitation) are observed>
To build this map, the team combined state-of-the-art 3D epigenome profiling with RNA sequencing and chromatin accessibility analyses, capturing how DNA folds and which regulatory elements contact target genes. They identified 55 stage-specific transcription factors that guide astrocyte maturation; among them, NR3C1 emerged as the critical ‘switch’ in early life. Notably, deleting NR3C1 in astrocytes did not disrupt normal development. However, when the adult mice were challenged with an autoimmune model of multiple sclerosis, animals lacking astrocytic NR3C1 mounted exaggerated inflammatory responses and developed more severe disease.
Mechanistically, the study shows that early loss of NR3C1 epigenetically primes immune genes - keeping their regulatory elements open and ready - so that later in life these genes respond too strongly to inflammatory cues. In effect, NR3C1 serves as an early ‘brake’ that prevents over-activation of astrocyte immune programs in adulthood.
“This is the first demonstration that astrocyte immune functions are governed by epigenetic memory,” said Professor Won-Suk Chung. “Our findings offer new clues to the origins of degenerative brain disorders, including Alzheimer’s disease.”
“We reveal a temporal regulatory window in astrocyte development that can set the stage for disease vulnerability in adulthood,” added Professor Inkyung Jung. “Understanding the 3D genome logic behind these programs could open paths to therapies for immune-related brain disorders such as multiple sclerosis.”
<The figure shows the three-dimensional genome structure of astrocytes at specific gene loci, illustrating how NR3C1 regulates their expression. In normal cells, NR3C1 binds to DNA and maintains the chromatin in a closed state, thereby preventing unnecessary activation between distal regulatory elements (enhancers) and gene promoters. In contrast, when NR3C1 is absent, the chromatin becomes open, creating a state in which enhancers and genes can be more easily activated. As a result, genes such as Mxi1 are overexpressed, triggering inflammatory responses. This clearly demonstrates that NR3C1 plays an essential role in maintaining immune homeostasis by stabilizing three-dimensional gene regulatory mechanisms.>
The results of this study were published online on September 22 in the international journal Nature Communications (IF 15.7), with Dr. Seongwan Park and PhD student Hyeonji Park of KAIST’s Department of Biological Sciences as co-first authors.
※ Paper title: “NR3C1-mediated epigenetic regulation suppresses astrocytic immune responses in mice,” DOI: https://www.nature.com/articles/s41467-025-64088-5
In addition, on September 17, the journal published a commentary article introducing this research: https://www.nature.com/articles/s41467-025-64102-w
This research was supported by the Suh Kyungbae Science Foundation, the Ministry of Health and Welfare, the Ministry of Science and ICT, and IBS.
Glossary - Epigenetic priming: preparing genes for rapid future activation by altering chromatin without changing DNA sequence
2025.09.25 View 3641 -
Accurate Real time ECG Measurement While Comfortably Lying Down at Home
< (From left) Professor Chul Kim of the Department of Bio and Brain Engineering, Ph.D. candidate Minjae Kim, researcher Premravee Teeravichayangoon >
KAIST's research team has developed a technology that can measure electrocardiogram (ECG) and heart rate variability (HRV) in real time by simply lying on a bed with clothes on, without having to go to the hospital. This technology is expected to evolve into a daily heart health monitoring platform in conjunction with remote healthcare, and further expand into various bio-healthcare fields such as sleep and stress analysis, contributing to personalized prevention and early diagnosis for patients.
KAIST announced on the 19th that Professor Chul Kim's research team from the Department of Bio and Brain Engineering has developed an 'in-bed cardiac monitoring on-device system'.
The research team manufactured a flexible substrate sensor that integrates the electronic circuit and electrodes into one to increase precision, and implemented an integrated system that can perform signal-noise separation, heart beat signal (R-peak) detection, and heart rate variability analysis in real time through on-device signal processing.
Existing ECG measurement had the inconvenience of visiting a hospital, taking off clothes, and attaching wet electrodes to the skin. Because of this, long-term monitoring was difficult, and it was not easy for the elderly or patients with chronic diseases to use it daily. Non-contact methods also had a technical limitation of being vulnerable to external noise.
To solve these problems, the research team applied a circuit that blocks external noise (active shielding) and a circuit that stably captures minute current changes in the human body (right-leg drive circuit). In addition, they implemented a mathematical transformation technique (wavelet transform) that extracts only the important parts from the heart beat signal and a calculation method (peak detection algorithm) that accurately identifies the moment of the heart's electrical beat (R-peak) as on-device signal processing techniques, allowing for precise real-time analysis of the signal.
As a result, users can obtain stable and accurate ECG signals even when lying on their backs with clothes on.
< Figure. Overall structural diagram of the developed non-contact in-bed cardiac monitoring on-device system, schematic diagram of the R-peak detection algorithm, real-time ECG and HRV measurement screen >
This research presents new possibilities for managing chronic cardiovascular diseases and supporting the health of the elderly, as it can be easily used not only in hospitals but also at home.
Professor Chul Kim said, "This system, which can extract signals in real time even in a noisy environment, can be used to easily check heart health in daily life," and added, "In the future, it will become the foundation of sleep health management by adding the measurement of various bio-signals."
This paper, in which Ph.D. candidate Minjae Kim and researcher Premravee Teeravichayangoon from the Department of Bio and Brain Engineering participated as co-first authors, was published online in the international journal 'Biosensors and Bioelectronics' on August 9, 2025.
※ Paper title: A homecare in-bed hardware system for precise real-time ECG and HRV monitoring with layered clothing. DOI: https://doi.org/10.1016/j.bios.2025.117838
※ Author information: Minjae Kim (KAIST Department of Bio and Brain Engineering, First Author), Premravee Teeravichayangoon (KAIST Department of Bio and Brain Engineering, First Author), Chul Kim (KAIST Department of Bio and Brain Engineering, Corresponding Author)
Meanwhile, this research was carried out with the support of the National Research Foundation of Korea's Basic Research Lab and Bio-medical Technology Development Project, and the KAIST-Ceragem Future Healthcare Research Center.
2025.09.19 View 1940