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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 286 -
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 404 -
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 575 -
Longevity mediated by suppressing age-associated circRNA
< (Back row from left) Prof. Yoon Ki Kim, Prof. Seung-Jae V. Lee, and Gwangrog Lee; (Front row from left) Dr. Sung Ho Boo, Sieun S. Kim, Seokjin Ham, and (top) Donghun Lee >
Cells in our bodies produce RNA based on genetic information stored in DNA, and RNA serves as a blueprint for making proteins. Researchers at our university have discovered a new phenomenon: removing 'circular RNA' that accumulates in cells as we age can slow down aging and extend lifespan. This study provides crucial clues for uncovering the principles of aging and developing treatment strategies for related diseases.
Professor Seung-Jae V. Lee’s research team (RNA-Mediated Healthspan and Longevity Research Center) from the Department of Biological Sciences, in collaboration with research teams led by Professors Yoon Ki Kim and Gwangrog Lee, announced on the 18th that they discovered the RNASEK protein—an enzyme that degrades circular RNA—plays a vital role in slowing aging and extending lifespan.
Until now, circular RNA has been regarded mainly as an aging marker because of its stability, which allows it to accumulate over time. However, the molecular mechanism for removing this RNA and its direct link to aging had not been clearly identified. The research team conducted this study to determine how the accumulation of circular RNA affects aging and whether an intracellular management system exists to regulate it.
Using Caenorhabditis elegans (C. elegans), a short-lived roundworm widely used in aging research, the team first confirmed that the circular RNA-degrading enzyme RNASEK is essential for longevity. They also discovered that as aging progresses, the amount of RNASEK decreases, resulting in an abnormal accumulation of circular RNA within cells.
Conversely, artificially increasing the levels of RNASEK (overexpression) extended the lifespan and allowed the organisms to survive longer in a healthy state. This implies that the process of appropriately removing cellular circular RNA is critical for maintaining health and longevity.
The research team also found that RNASEK prevents the toxic aggregation of circular RNAs in aged organisms. . When RNASEK is deficient and circular RNA accumulates, "stress granules" form abnormally inside the cell, which can impair cellular functions and accelerate aging.
RNASEK works alongside the chaperone protein HSP90 (which helps proteins avoid misfolding or clumping) to inhibit the formation of these stress granules and help cells maintain a normal state. Notably, this phenomenon was observed not only in C. elegans but also in human cells. In mammals, RNASEK also functions to directly degrade circular RNA; a deficiency of RNASEK in human cells and mouse models led to premature aging.
< Diagram showing progress toward longevity or aging depending on circular RNA and the removal enzyme RNASEK >
The researchers explained that this study is significant as it identifies a mechanism for regulating aging at the RNA level. They suggested that research using RNASEK to control circular RNA could lead to the development of treatment strategies for human aging and degenerative diseases.
Professor Seung-Jae V. Lee of KAIST, who led the study, explained, "Until now, circular RNA was merely regarded as a marker of aging that accumulates over time due to its stability. This study proves that circular RNA accumulated during aging actually induces aging, and that RNASEK, which removes it, is a key regulator that slows aging and induces healthy longevity."
< (AI-generated image) Longevity induced by the circular RNA-removing enzyme RNASEK >
Drs. Sieun S. Kim, Seokjin Ham, Sung Ho Boo, and Donghun Lee from the KAIST Department of Biological Sciences participated as joint first authors. The research results were published on February 24 in the world-renowned scientific journal Molecular Cell.
Paper Title: Ribonuclease $\kappa$ promotes longevity by preventing age-associated accumulation of circular RNA in stress granules
DOI: 10.1016/j.molcel.2026.01.031
This research was conducted with support from the Leader Researcher Program of the National Research Foundation of Korea.
2026.03.18 View 1681 -
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 2377 -
Unraveling the Secret of Cell Movement
<(From left) Professor Won Do Heo (KAIST), Postdoctoral Researcher Heeyoung Lee (KAIST, First Author), Professor Kwang-Hyun Cho (KAIST), Professor Kapsang Lee (Johns Hopkins University, USA), Dr. Sangkyu Lee (IBS), Dr. Dongsan Kim (LIBD), Dr. Yeaji Seo (Hulux) (Co-First Authors)>
Cell movement is an essential biological process, whether it's cancer cells metastasizing to other parts of the body or immune cells migrating to heal a wound. However, the principle by which cells autonomously determine their direction of movement without external stimuli has remained unknown until now.
Through this research, KAIST and an international joint research team have elucidated the principle by which cells decide their direction and move on their own, offering a crucial clue for identifying the causes of cancer metastasis and immune diseases and establishing new treatment strategies.
KAIST announced on the 10th of November that the research team led by Endowed Chair Professor Won Do Heo of the Department of Biological Sciences, in collaboration with the research team of Endowed Chair Professor Kwang-Hyun Cho of the Department of Bio and Brain Engineering, and Professor Kapsang Lee's research team at Johns Hopkins University in the US, has for the first time in the world identified the 'autonomous driving mechanism' by which cells determine their direction of movement without external signals.
The research team developed a new imaging technique called 'INSPECT (INtracellular Separation of Protein Engineered Condensation Technique)' that allows direct visualization of how proteins interact within living cells. Using this technology, they revealed the principle of the cell's internal program for autonomously deciding its direction of movement.
The team newly analyzed the operation of the key proteins that regulate cell movement, the Rho family proteins (Rac1, Cdc42, RhoA). The results showed that these proteins do not merely divide the front and back of the cell, as previously theorized, but that the cell's decision to move straight or change direction depends on which protein it binds with.
The INSPECT technology artificially implements the phenomenon of 'phase separation,' where proteins, upon binding, naturally form segregated regions that do not mix well. This technique allows for the direct visualization of how proteins actually bind within the cell using a fluorescent signal.
<Figure 1. INSPECT: A technique for visualizing Intracellular Protein-Protein Interactions">
The research team used the proteins ferritin and the fluorescent protein DsRed to make the clusters, or 'condensates,' visible to the eye when proteins bind together like small droplets.
Using this technology, the team analyzed a total of 285 pairs of interactions by combining 15 types of Rho proteins with 19 types of binding proteins, confirming actual binding in 139 pairs. Specifically, they identified that the Cdc42–FMNL protein combination is the core circuit responsible for the cell's 'straight movement,' while the Rac1–ROCK protein combination is responsible for the cell's 'change of direction.'
The research team slightly modified a part of the Rac1 protein (the 37th amino acid), which is crucial for cell direction control, to prevent it from binding well with the 'steering wheel' protein, ROCK. As a result, the cells could not change direction and continued to move in a straight line.
In contrast, in normal cells, Rac1 and ROCK bind well, forming a structure called 'arc stress fiber' at the front of the cell. This fiber enables the cell to make near-perpendicular turns when changing direction.
Furthermore, in an experiment where the environment the cells were attached to was changed, normal cells adjusted their moving speed according to the surrounding environment, but the Rac1F37W cells (cells with a broken 'steering wheel') maintained the same speed regardless of environmental changes. This demonstrates that the Rac–ROCK protein axis subtly controls the cell's ability to recognize and adapt to its surrounding environment.
<Figure 2. Analysis of the Signaling Network through Screening of Protein Interactions that Bind to a Cell Migration-Controlling Protein>
Professor Won Do Heo stated, "This research reveals that cell movement is not a random motion but is precisely controlled by an intrinsic program created by the ensemble of Rho signaling proteins and cell migration-related proteins." He added, "The newly developed INSPECT technology is a powerful tool for visualizing intracellular protein interactions and will be broadly utilized to uncover the molecular mechanisms of various life phenomena and diseases, such as cancer metastasis and neuronal cell migration."
This research, in which Dr. Heeyoung Lee of KAIST, Dr. Sangkyu Lee (currently at IBS), Dr. Yeji Seo (currently at Hulux Co., Ltd.), and Dr. Dongsan Kim (currently at LIBD) participated as co-first authors, was published in Nature Communications on October 31st.
Journal Name: A Rho GTPase-effector ensemble governs cell migration behavior
DOI: https://doi.org/10.1038/s41467-025-64635-0
The research was supported by the Samsung Future Technology Foundation and the National Research Foundation of Korea.
2025.11.10 View 2017 -
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 3084 -
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 3609 -
A Breakthrough in Parkinson's Research: Precision Diagnosis and Treatment with AI and Optogenetics
<Research team photo (from top left) Dr. Bobae Hyeon, Professor Daesoo Kim, Director Chang-joon Lee, (right) Professor Won Do Heo>
Globally recognized figures like Muhammad Ali and Michael J. Fox have long suffered from Parkinson's disease. The disease presents a complex set of motor symptoms, including tremors, rigidity, bradykinesia, and postural instability. However, traditional diagnostic methods have struggled to sensitively detect changes in the early stages, and drugs targeting brain signal regulation have had limited clinical effectiveness.
Recently, Korean researchers successfully demonstrated the potential of a technology that integrates AI and optogenetics as a tool for precise diagnosis and therapeutic evaluation of Parkinson's disease in mice. They have also proposed a strategy for developing next-generation personalized treatments.
KAIST (President Kwang Hyung Lee) announced on the 22nd of September that a collaborative research team—comprising Professor Won Do Heo's team from the Department of Biological Sciences, Professor Daesoo Kim's team from the Department of Brain and Cognitive Sciences, and Director Chang-Jun Lee's team from the Institute for Basic Science (IBS) Center for Cognition and Sociality—achieved a preclinical research breakthrough by combining AI analysis with optogenetics. Their work simultaneously demonstrated the possibility of early and precise diagnosis and treatment in an animal model of Parkinson's disease.
The research team created a Parkinson's disease mouse model with two stages of severity. These were male mice with alpha-synuclein protein abnormalities, a standard model used to simulate human Parkinson's disease for diagnostic and therapeutic research.
In collaboration with Professor Kim's team at KAIST, they introduced AI-based 3D pose estimation for behavioral analysis. The team analyzed over 340 behavioral features—such as gait, limb movements, and tremors—from the Parkinson's mice and condensed them into a single metric: the AI-predicted Parkinson's disease score (APS).
The analysis showed that the APS exhibited a significant difference from the control group as early as two weeks after the disease was induced. It also proved more sensitive in assessing the disease's severity than traditional motor function tests. The study identified key diagnostic features, including changes in stride, asymmetrical limb movements, and chest tremors. The top 20 behavioral features included hand/foot asymmetry, changes in stride and posture, and an increase in high-frequency chest movement.
To confirm that these behavioral indicators were not just general motor decline but specific to Parkinson's, the team applied the same analysis to a mouse model of Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, in collaboration with Director Lee's team at IBS. Since both Parkinson's and ALS cause motor function problems, if the APS simply reflected poor motor skills, a high score should have appeared in both diseases.
However, the analysis of the ALS animal model showed that despite a decline in motor function, the mice did not exhibit the high APS seen in the Parkinson's model. Instead, their scores remained low, and their behavioral changes were distinctly different. This demonstrates that APS is directly related to specific, characteristic changes that only appear in Parkinson's disease.
For treatment, the research team used optoRET, an optogenetics technology that precisely controls neurotrophic signals with light. This technique proved effective in the animal model, leading to smoother gait and limb movements and a reduction in tremors.
Specifically, a regimen of shining light on alternate days was found to be the most effective, and it also showed a tendency to protect dopamine-producing neurons in the brain.
Professor Won Do Heo of KAIST stated, "This is the first time in the world that a preclinical framework has been implemented that connects early diagnosis, treatment evaluation, and mechanism verification of Parkinson's disease by combining AI-based behavioral analysis with optogenetics." He added, "This lays a crucial foundation for future personalized medicine and customized treatments for patients."
The study, with Dr. Bobae Hyeon, a postdoctoral researcher at the KAIST Institute for Biological Science, as the first author, was published online in the international journal Nature Communications on August 21st. Dr. Hyeon is conducting follow-up research to advance Parkinson's cell therapy at McLean Hospital, Harvard Medical School, supported by the "Global Physician-Scientist Training Program" of the Korea Health Industry Development Institute.
This research was supported by the KAIST Global Singularity Project, the Ministry of Science and ICT/National Research Foundation of Korea, the IBS Center for Cognition and Sociality, and the Ministry of Health and Welfare/Korea Health Industry Development Institute.
Paper Title: Integrating artificial intelligence and optogenetics for Parkinson's disease diagnosis and therapeutics in male mice
DOI: https://doi.org/10.1038/s41467-025-63025-w
2025.09.22 View 2563 -
KAIST Identifies Key to Slowing Aging via RNA Regulation... Unlocks Mechanism for Longevity
As aging progresses, the quality of DNA and proteins inside cells declines, known to be the cause of various degenerative diseases. However, the connection between aging and RNA has remained largely unexplored. Now, a Korean research team has discovered that a ribosome-associated quality control factor—PELOTA, a protein essential for eliminating abnormal mRNA—plays a central role in slowing aging and promoting longevity. This breakthrough is expected to provide a new direction for future therapeutic strategies targeting human aging and neurodegenerative diseases.
KAIST (President Kwang Hyung Lee) announced that a joint research team—led by Professor Seung-Jae V. Lee of the Department of Biological Sciences at KAIST and the Research Center for RNA-mediated Healthy Longevity, Professor Jinsoo Seo of Yonsei University (President Dong-Sup Yoon), and Professor Kwang-Pyo Lee of the Korea Research Institute of Bioscience and Biotechnology (KRIBB, President Suk Yoon Kwon) under the National Research Council of Science & Technology (NST, Chairman Yeung-Shik Kim—has discovered that the protein ‘PELOTA*’, which plays a key role in ribosome-associated quality control, regulates the pace of aging.
*PELOTA: A key protein in maintaining cellular translational homeostasis, responsible for detecting and resolving errors during mRNA translation by ribosomes.
Until now, RNA—particularly mRNA—has generally been regarded as a transient intermediary in protein synthesis. Its instability made it difficult to study quantitatively or track over time, leaving its physiological and functional roles relatively understudied compared to DNA.
Using C. elegans (a nematode widely used in aging research due to its short lifespan), the researchers first discovered that the ribosome-associated quality control factor PELOTA is essential for longevity. In particular, when PELOTA was overexpressed in normal nematodes, their lifespan was extended, suggesting that ribosome-associated quality control mechanisms involved in removing abnormal mRNA are necessary for promoting longevity.
The study also revealed that the ribosome-associated quality control system simultaneously regulates both the mTOR signaling pathway—which senses nutrient status or growth signals to control cell growth, protein synthesis, and autophagy, and plays a key role in aging and energy metabolism—and the autophagy pathway, the cellular cleanup and recycling system through which cells break down and reuse unnecessary or damaged components.
When PELOTA was deficient, the mTOR pathway became abnormally activated, and autophagy was suppressed—accelerating aging. Conversely, activation of PELOTA inhibited mTOR and induced autophagy, thereby maintaining cellular homeostasis and extending lifespan.
Notably, this mechanism was found to be conserved in both mice and humans. The study also showed that the loss of PELOTA could contribute to muscle aging and Alzheimer’s disease, suggesting its relevance to age-related disorders.
These findings indicate that the study of PELOTA and ribosome-associated quality control could play an important role in developing therapeutic strategies for human aging and neurodegenerative diseases.
Professor Seung-Jae V. Lee of KAIST, who led the research, stated, “While the connection between quality control and aging has been well established at the DNA and protein levels, molecular evidence showing that RNA quality control also functionally contributes to lifespan regulation has been very limited.” He emphasized that the “study provides strong evidence that the removal of abnormal RNA is a central axis in the aging regulatory network.”
The study was published on August 5th in the prestigious journal PNAS (Proceedings of the National Academy of Sciences), with Dr. Jongsun Lee and Dr. Eun Ji Kim of KAIST, Dr. Bora Lee of KRIBB, and Dr. Hyein Lee of Yonsei University as co-first authors.
※ Title: Pelota-mediated ribosome-associated quality control counteracts aging and age-associated pathologies across species ※ DOI: https://doi.org/10.1073/pnas.2505217122
This research was supported by the Global Leader Research Project of the National Research Foundation of Korea.
2025.08.18 View 4670 -
KAIST Reveals Placental Inflammation as the Cause of Allergies such as Pediatric Asthma
<(From left)Professor Heung-kyu Lee from the Department of Biological Sciences, Dr.Myeong Seung Kwon from the Graduate School of Medical Science>
It is already well-known that when a mother experiences inflammation during pregnancy, her child is more likely to develop allergic diseases. Recently, a KAIST research team became the first in the world to discover that inflammation within the placenta affects the fetus's immune system, leading to the child exhibiting excessive allergic reactions after birth. This study presents a new possibility for the early prediction and prevention of allergic diseases such as pediatric asthma.
KAIST (President Kwang Hyung Lee) announced on the 4th of August that a research team led by Professor Heung-kyu Lee from the Department of Biological Sciences found that inflammation occurring during pregnancy affects the fetus's stress response regulation system through the placenta. As a result, the survival and memory differentiation of T cells (key cells in the adaptive immune system) increase, which can lead to stronger allergic reactions in the child after birth.
The research team proved this through experiments on mice that had excessive inflammation induced during pregnancy. First, they injected the toxin component 'LPS (lipopolysaccharide),' a substance known to be a representative material that induces an inflammatory response in the immune system, into the mice to cause an inflammatory response in their bodies, which also caused inflammation in the placenta.
It was confirmed that the placental tissue, due to the inflammatory response, increased a signaling substance called 'Tumor Necrosis Factor-alpha (TNF-α),' and this substance activated immune cells called 'neutrophils*', causing inflammatory damage to the placenta. *Neutrophils: The most abundant type of white blood cells in our bodies (40-75%), playing an important role in innate immunity and killing invading bacteria and fungi.
This damage modulated postnatal offspring stress response, leading to a large secretion of stress hormone (glucocorticoid). As a result, the offspring's T cells, which are responsible for immune memory, survived longer and had stronger memory functions.
In particular, the memory T cells created through this process caused excessive allergic reactions when repeatedly exposed to antigens after birth. Specifically, when house dust mite 'allergens' were exposed to the airways of mice, a strong eosinophilic inflammatory response and excessive immune activation were observed, with an increase in immune cells important for allergy and asthma reactions.
Professor Heung Kyu Lee stated, "This study is the first in the world to identify how a mother's inflammatory response during pregnancy affects the fetus's allergic immune system through the placenta." He added, "This will be an important scientific basis for developing biomarkers for early prediction and establishing prevention strategies for pediatric allergic diseases."
The first author of this study is Dr. Myeong Seung Kwon from the KAIST Graduate School of Medical Science (currently a clinical fellow of gynecological oncology at Konyang University Hospital's Department of Obstetrics and Gynecology), and the research results were published in the authoritative journal in the field of mucosal immunology, 'Mucosal Immunology,' on July 1st. ※ Paper Title: Placental inflammation-driven T cell memory formation promotes allergic responses in offspring via endogenous glucocorticoids ※ DOI: https://doi.org/10.1016/j.mucimm.2025.06.006
This research was conducted as part of the Basic Science Research Program and the Bio-Medical Technology Development Program supported by the Ministry of Science and ICT and the National Research Foundation of Korea.
2025.08.03 View 2545 -
KAIST Shows That the Brain Can Distinguish Glucose: Clues to Treat Obesity and Diabetes
<(From left)Prof. Greg S.B Suh, Dr. Jieun Kim, Dr. Shinhye Kim, Researcher Wongyo Jeong)
“How does our brain distinguish glucose from the many nutrients absorbed in the gut?” Starting with this question, a KAIST research team has demonstrated that the brain can selectively recognize specific nutrients—particularly glucose—beyond simply detecting total calorie content. This study is expected to offer a new paradigm for appetite control and the treatment of metabolic diseases.
On the 9th, KAIST (President Kwang Hyung Lee) announced that Professor Greg S.B. Suh’s team in the Department of Biological Sciences, in collaboration with Professor Young-Gyun Park’s team (BarNeuro), Professor Seung-Hee Lee’s team (Department of Biological Sciences), and the Albert Einstein College of Medicine in New York, had identified the existence of a gut-brain circuit that allows animals in a hungry state to selectively detect and prefer glucose in the gut.
Organisms derive energy from various nutrients including sugars, proteins, and fats. Previous studies have shown that total caloric information in the gut suppresses hunger neurons in the hypothalamus to regulate appetite. However, the existence of a gut-brain circuit that specifically responds to glucose and corresponding brain cells had not been demonstrated until now.
In this study, the team successfully identified a “gut-brain circuit” that senses glucose—essential for brain function—and regulates food intake behavior for required nutrients.
They further proved, for the first time, that this circuit responds within seconds to not only hunger or external stimuli but also to specific caloric nutrients directly introduced into the small intestine, particularly D-glucose, through the activity of “CRF neurons*” in the brain’s hypothalamus.
*CRF neurons: These neurons secrete corticotropin-releasing factor (CRF) in the hypothalamus and are central to the hypothalamic-pituitary-adrenal (HPA) axis, the body’s core physiological system for responding to stress. CRF neurons are known to regulate neuroendocrine balance in response to stress stimuli.
Using optogenetics to precisely track neural activity in real time, the researchers injected various nutrients—D-glucose, L-glucose, amino acids, and fats—directly into the small intestines of mice and observed the results.
They discovered that among the CRF neurons located in the paraventricular nucleus (PVN)* of the hypothalamus, only those specific to D-glucose showed selective responses. These neurons did not respond—or showed inverse reactions—to other sugars or to proteins and fats. This is the first demonstration that single neurons in the brain can guide nutrient-specific responses depending on gut nutrient influx.
*PVN (Paraventricular Nucleus): A key nucleus within the hypothalamus responsible for maintaining bodily homeostasis.
The team also revealed that glucose-sensing signals in the small intestine are transmitted via the spinal cord to the dorsolateral parabrachial nucleus (PBNdl) of the brain, and from there to CRF neurons in the PVN. In contrast, signals for amino acids and fats are transmitted to the brain through the vagus nerve, a different pathway.
In optogenetic inhibition experiments, suppressing CRF neurons in fasting mice eliminated their preference for glucose, proving that this circuit is essential for glucose-specific nutrient preference.
This study was inspired by Professor Suh’s earlier research at NYU using fruit flies, where he identified “DH44 neurons” that selectively detect glucose and sugar in the gut. Based on the hypothesis that hypothalamic neurons in mammals would show similar functional responses to glucose, the current study was launched.
To test this hypothesis, Dr. Jineun Kim (KAIST Ph.D. graduate, now at Caltech) demonstrated during her doctoral research that hungry mice preferred glucose among various intragastrically infused nutrients and that CRF neurons exhibited rapid and specific responses.
Along with Wongyo Jung (KAIST B.S. graduate, now Ph.D. student at Caltech), they modeled and experimentally confirmed the critical role of CRF neurons. Dr. Shinhye Kim, through collaboration, revealed that specific spinal neurons play a key role in conveying intestinal nutrient information to the brain.
Dr. Jineun Kim and Dr. Shinhye Kim said, “This study started from a simple but fundamental question—‘How does the brain distinguish glucose from various nutrients absorbed in the gut?’ We have shown that spinal-based gut-brain circuits play a central role in energy metabolism and homeostasis by transmitting specific gut nutrient signals to the brain.”
Professor Suh added, “By identifying a gut-brain pathway specialized for glucose, this research offers a new therapeutic target for metabolic diseases such as obesity and diabetes. Our future research will explore similar circuits for sensing other essential nutrients like amino acids and fats and their interaction mechanisms.”
Ph.D. student Jineun Kim, Dr. Shinhye Kim, and student Wongyo Jung (co-first authors) contributed to this study, which was published online in the international journal Neuron on June 20, 2025.
※ Paper Title: Encoding the glucose identity by discrete hypothalamic neurons via the gut-brain axis ※ DOI: https://doi.org/10.1016/j.neuron.2025.05.024
This study was supported by the Samsung Science & Technology Foundation, the National Research Foundation of Korea (NRF) Leader Research Program, the POSCO Cheongam Science Fellowship, the Asan Foundation Biomedical Science Scholarship, the Institute for Basic Science (IBS), and the KAIST KAIX program.
2025.07.09 View 3706