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KAIST Develops a Way to Combat Cancer Cachexia, the Wasting Syndrome That Debilitates Patients
A new path has opened toward stopping cancer-associated cachexia, a devastating complication that gradually wastes patients away. A KAIST research team has developed an RNA-based therapeutic strategy that blocks a brain signal to prevent muscle loss and extend survival.
KAIST (President Choongsik Bae) announced on the 2nd of August that a joint research team led by Professor Minho Shong and Professor Jinkuk Kim from the Graduate School of Medical Science and Engineering, together with the KAIST faculty startup THOR Therapeutics (CEO Minho Shong), identified a new therapeutic principle for cancer cachexia.
Cancer cachexia affects 50 to 80 percent of all cancer patients, making it one of the most common complications of the disease. As cancer cells disrupt the body's metabolism, patients continue to lose weight and muscle mass even when eating sufficiently, leading to severe physical decline. This is a major reason chemotherapy often becomes less effective and treatment is discontinued, ultimately lowering survival rates. Existing drugs, however, have been limited to temporarily boosting appetite and have failed to fundamentally address the underlying muscle loss and metabolic dysfunction.
The research team focused on the idea that the root cause of cancer cachexia lies not in the body, but in the brain. The team noted that when GDF15 (Growth Differentiation Factor 15)—a signaling protein secreted in large amounts as cancer progresses—binds to GFRAL, a receptor protein in the brainstem, it triggers a signal instructing the body to stop eating and instead break down stored muscle and fat, driving progressive physical decline.
To block this process, the team worked with Professor Kim's group to develop a therapeutic using antisense oligonucleotides (ASO)—an RNA-based gene therapy technologies that selectively suppresses the activity of a specific gene—to prevent GFRAL from being produced in the first place.
In effect, the treatment switches off the receiver of the signal that cancer cells send instructing the body to waste away. By blocking GFRAL production at the RNA stage—the intermediate step in which genetic information is converted into protein—the therapy shuts down the cachexia-inducing signal at its source.
The team administered the treatment to mice in which cancer cachexia had already progressed. The result was a substantial reduction in muscle and fat loss, along with the restoration of the metabolic function that had previously broken down. Notably, even though treatment began after the disease had advanced significantly, survival at the study's endpoint (around day 50) was markedly higher in the treated group—90 percent—compared with just 20 percent in the untreated group, demonstrating the therapy's potential for treating cancer cachexia.
Unlike existing treatments that only stimulate appetite, this study is significant in that it blocks the underlying signal driving the wasting process itself. The therapy improved both muscle loss and metabolic dysfunction, and researchers expect that it could eventually be used alongside existing cancer treatments as a next-generation adjuvant therapy to improve patients' quality of life, treatment effectiveness, and survival rates.
"While existing therapies have only temporarily boosted appetite, this study is significant in that it directly targeted a key receptor in the brainstem at the RNA level to suppress the root cause of cancer cachexia," said Professor Song. He added that the team's goal is to move forward with follow-up preclinical research and drug manufacturing as well as quality-control systems without delay, begin clinical development in cancer patients by 2030, and develop the therapy into a treatment that improves patients' quality of life and survival rates.
Dr. Hyunjung Hong from the Graduate School of Medical Science and Engineering, Dr. Minhee Lee from THOR Therapeutics, and Dr. Minsung Park from the Graduate School of Medical Science and Engineering participated as co-first authors, with Professor Song and Professor Kim serving as co-corresponding authors. The findings were published in the international journal Cell Reports Medicine on July 27.
Paper title: Therapeutic Gfral silencing via antisense oligonucleotides ameliorates cancer-associated cachexia and extends survival in tumor-bearing mice
DOI : https://doi.org/10.1016/j.xcrm.2026.102939
This research was supported by the National Research Foundation of Korea, the Korea Health Industry Development Institute, and the Ministry of SMEs and Startups.
2026.08.03 View 513 -
KAIST Gives Antibodies “Eyes” to Detect Cancer, Targeting Cancer Mutations Inside Cells
Antibodies are like “guided missiles” that find and attack cancer cells, but cancer-causing mutations inside cells have remained a “blind spot” for treatment because antibodies cannot reach them. KAIST researchers have now succeeded in precisely targeting even intracellular cancer mutations using a newly designed antibody created through computational methods. This achievement is expected to open a new path toward next-generation precision therapies for difficult-to-treat cancers, going beyond the limitations of conventional antibody treatments.
KAIST (President Choongsik Bae) announced on the 24th of July that a research team led by Professor Byung-Ha Oh from the Department of Biological Sciences, together with researchers from Therazyne, a KAIST faculty startup specializing in protein design and headed by Professor Oh, has developed an antibody that selectively recognizes only cancer cells carrying KRAS(G12D), a representative cancer-driving mutation. By combining computational antibody design with experimental validation, the team designed a new antibody that would have been difficult to develop through conventional approaches and is now verifying its efficacy in animal disease models.
KRAS(G12D) is a mutated form of the KRAS protein, which regulates cell growth and proliferation. It is one of the most common cancer-driving mutations found in pancreatic, colorectal, and lung cancers. However, because the KRAS protein exists inside cells, it has long been considered an “undruggable target” that is difficult to directly target with conventional antibody therapeutics.
The research team focused on the natural process by which cells break down aged or damaged proteins into small fragments. The KRAS(G12D) protein inside cells is also processed in this way into small protein fragments, known as neoantigens, which serve as clues that allow immune cells to distinguish cancer cells. Some of these fragments are then transported to the cell surface and presented to immune cells. By combining computational protein design with experimental screening, the team developed a TCR-like antibody that precisely recognizes only this cancer-mutation-derived fragment.
TCR, or T cell receptor, acts as a “sensor” that allows T cells, the body’s immune cells, to read protein fragments displayed on the surface of cells and identify cancer cells or virus-infected cells. The TCR-like antibody developed in this study works on a similar principle, effectively giving an antibody the “eyes” of a T cell. It was designed to selectively recognize traces of intracellular cancer mutations that conventional antibodies cannot easily access.
Experimental results confirmed that the antibody developed by the team selectively recognizes only cancer cells carrying the KRAS(G12D) mutation, while showing little to no reaction with normal cells or other proteins. When applied to immunotherapy, it was also shown to effectively eliminate only cancer cells carrying the mutation. This finding suggests the possibility of expanding antibody therapy to intracellular cancer-driving proteins that conventional antibody treatments have been unable to target. It is also expected to serve as a platform technology for developing next-generation precision antibody therapies targeting not only KRAS but also a wide range of cancer mutations.
Professor Byung-Ha Oh said, “The antibody developed in this study can selectively identify only cancer cells carrying the KRAS(G12D) mutation, demonstrating the potential for precision antibody therapeutics that minimize damage to normal cells.” He added, “The computational antibody design technology developed in this research is expected to be widely applicable to the development of next-generation antibody therapeutics targeting KRAS as well as various other cancer mutations.”
Both the first author and corresponding authors of this study are KAIST-affiliated researchers. SangPhil Ahn, a researcher at Therazyne, participated as the first author, while Professor Byung-Ha Oh and Bo-Seong Jeong, Head of Research at Therazyne, jointly led the study as co-corresponding authors. The research was published online on June 3 in Molecular Therapy, a leading international journal in the field of gene and cell therapy.
Paper title: Discovery of TCR-like antibodies to the KRAS G12D neoantigen via in silico-in vitro workflow DOI: https://doi.org/10.1016/j.ymthe.2026.05.032
This research was conducted in collaboration with Therazyne and the New Drug Development Center of the Osong Biomedical Innovation Foundation, and was supported by the Ministry of Science and ICT’s Industry-Academia-Research Linked New Drug Development Program and the National Research Foundation of Korea’s Bio & Medical Technology Development Program.
2026.07.24 View 1173 -
A Single Blood Sample May Improve the Prediction of Colorectal Cancer Recurrence and Progression, KAIST Study Finds
A single preoperative blood sample may help improve the prediction of recurrence or metastasis in patients with colorectal cancer. A joint research team from KAIST, Gangnam Severance Hospital, and Asan Medical Center has shown that, as colorectal cancer advances, the network of relationships among circulating amino acids (a kind of metabolic map) undergoes systematic remodeling. Building on this finding, the researchers developed an analytical method that showed higher predictive performance than a CEA-only model and models based solely on individual amino acid levels.
KAIST (President Choongsik Bae) announced on July 22 that a joint research team led by Professor Ji Min Lee from the Graduate School of Medical Science and Engineering and Professor Hyunwoo Kim from the Department of Chemistry, in collaboration with researchers at Gangnam Severance Hospital and Asan Medical Center, has developed a new framework for analyzing networks of circulating amino acids, which reflect the body’s metabolic state. Using this framework, the team showed that the circulating amino acid network undergoes stage-dependent remodeling that reflects systemic metabolic reprogramming. The team then used these network-derived features to develop a new analytical strategy for predicting recurrence or metastasis.
Cancer cells require large amounts of nutrients to grow and proliferate. Amino acids are not only the building blocks of proteins but also essential for energy production and DNA synthesis, making them critical to cancer cell survival and growth. Colorectal cancer, in particular, is characterized by pronounced changes in amino acid metabolism.
These changes are not confined to tumor tissue; they also appear in the bloodstream. As a result, blood amino acids have drawn attention as an important metabolic biomarker reflecting the body's overall metabolic state. Until now, however, research has focused mainly on the concentrations of individual amino acids, leaving the question of how amino acids are interconnected and change together largely unexplored.
The team used fluorine-19 nuclear magnetic resonance (¹⁹F NMR) spectroscopy to simultaneously quantify 18 circulating amino acids in a small serum sample. By analyzing not only the relative abundance of each amino acid but also the relationships among them as a network, the researchers showed that the circulating amino acid network is progressively remodeled as colorectal cancer advances.
The researchers interpreted this remodeling as evidence of systemic metabolic reprogramming (broad changes in metabolism associated with tumor progression).
As colorectal cancer progressed, the proportion of branched-chain amino acids (BCAAs) such as valine and leucine, which play key roles in muscle and energy metabolism, decreased, while the proportion of glycine and serine, which cancer cells need to synthesize DNA and proliferate rapidly, increased. This shift suggests that systemic amino acid utilization changes with advancing disease.
Glycine proved particularly notable. Although glycine is actively used by rapidly proliferating cancer cells, its relative abundance in the blood increased rather than decreased. The team also observed the emergence of a glycine-centered interaction pattern, providing further evidence of systemic metabolic remodeling during colorectal cancer progression.
The team then applied the pairwise amino acid interaction features into machine-learning models designed to identify patients with recurrence or metastasis.
In nested cross-validation, the correlation-based model showed higher predictive performance than a CEA-only model, while the combined model incorporating CEA, individual amino acid levels, and interaction-derived features achieved the highest overall performance. It also outperformed a model based solely on individual amino acid levels.
The findings suggest that examining how amino acids interact and change together, rather than considering their levels alone, provides a more informative picture of cancer progression. The study is the first to show that the interaction network among circulating amino acids could serve as a blood-based metabolic biomarker.
"We hope this will lead to new precision medicine technologies that can predict recurrence risk more accurately using a blood sample alone and help establish personalized treatment strategies," said Professor Ji Min Lee.
The research began with an interdisciplinary idea proposed through KAIST’s Master’s and PhD Venture Research Program. Graduate students in medical science and chemistry jointly conceived an interdisciplinary approach to studying cancer progression through networks of circulating amino acids. The proposal was selected for support and ultimately led to publication in the internationally renowned journal Advanced Science.
"This research embodies the spirit of KAIST by showing how students’ creative ideas and interdisciplinary collaboration can open new possibilities,” said KAIST President Choongsik Bae. He added that KAIST will continue to foster an environment in which students and researchers can freely pursue challenges across disciplinary boundaries and support creative interdisciplinary research that produces innovative technologies contributing to public health and quality of life.
The study's co-first authors are Ji-Yeon Lee, a student in the integrated master’s and doctoral program at the Graduate School of Medical Science and Engineering, and Dr. Jumi Kim, a postdoctoral researcher in the Department of Chemistry. Professors Ji Min Lee and Hyunwoo Kim of KAIST and Professor Eun Jung Park, affiliated with Gangnam Severance Hospital and Asan Medical Center, served as co-corresponding authors. The findings were published online in Advanced Science, which has a Journal Impact Factor of 14.1, on June 9, 2026.
Paper title: Circulating Amino Acid Network Remodeling Reveals Systemic Metabolic Reprogramming Predictive of Colorectal Cancer Recurrence and Metastasis
DOI: 10.1002/advs.76044
This research was supported by the Samsung Research Funding & Incubation Center of Samsung Electronics, the National Research Foundation of Korea, a Faculty Research Grant from the Department of Surgery at Asan Medical Center, and grants from the Asan Institute for Life Sciences, among others.
2026.07.22 View 979 -
KAIST Uncovers the “Hidden Key” to Immunotherapy for Intractable Brain Tumors
Researchers have uncovered a clue to why immune checkpoint inhibitors—cancer therapies that release the immune “brakes” exploited by tumors to evade attack—show limited efficacy in some brain tumors. A KAIST research team found that B cell and antibody responses initiated in tumor-draining lymph nodes, rather than T cells alone, are critical to the antitumor effects of anti-CTLA-4 therapy, opening a new avenue for treating intractable brain tumors.
KAIST (President Choongsik Bae) announced on the 19th of July that a research team led by Professor Heung Kyu Lee from the Department of Biological Sciences has identified a previously unrecognized immune mechanism through which anti-CTLA-4, a type of immune checkpoint inhibitor, promotes B-cell responses in tumor-draining lymph nodes, thereby helping the immune system attack brain tumors.
Glioblastoma is one of the most aggressive malignant brain tumors, with frequent recurrence and a poor prognosis even after surgery and radiation therapy. Immune checkpoint inhibitors, which restore the ability of immune cells to attack cancer cells, have produced substantial therapeutic benefits in various cancers. However, their effectiveness in glioblastoma has remained limited because of the highly immunosuppressive environment surrounding the tumor.
Researchers have traditionally regarded T cells—immune cells that can directly attack cancer cells—as the primary target of immune checkpoint inhibitors. B cells, meanwhile, are well known for producing antibodies following infection or vaccination, but their role in brain tumor immunotherapy has remained largely unexplored. The research team therefore investigated whether anti-CTLA-4 could influence B-cell responses as well as T-cell responses.
The findings challenged the prevailing T-cell-centered view. In mouse glioma models, anti-CTLA-4 treatment reduced tumor burden and significantly prolonged survival. However, these therapeutic effects were largely lost in mice lacking B cells, demonstrating that B cells are required for the efficacy of anti-CTLA-4 treatment in these models.
The team also identified where B cells played their key role. Rather than being prominent in the brain, where the tumor cells were located, the response increased markedly in the Deep Cervical Lymph Nodes, which are located deep in the neck and receive lymphatic drainage from the brain. In particular, germinal center B cells and T follicular helper cells, both of which are important for antibody formation, increased together in these lymph nodes. This was accompanied by an increase in immunoglobulin G, or IgG, responses. IgG is a major class of antibody that can recognize cancer cells as targets and help immune cells eliminate them.
The resulting IgG antibodies bound to the surface of glioma cells, helping macrophages—immune cells that engulf foreign substances and cancer cells—remove the tumor cells more effectively.
The research team also examined this process directly in vivo. Using a specialized dual-reporter glioma model expressing the red fluorescent protein mCherry and the green fluorescent protein EGFP, the researchers successfully visualized tumor-infiltrating phagocytes actively engulfing glioma cells following anti-CTLA-4 treatment.
The study provides the first functional evidence that B-cell immune responses—previously known mainly for their roles in infection and vaccination—can be a key factor determining the effectiveness of immunotherapy for hard-to-treat brain tumors. It also expands the conventional T-cell-centered framework of cancer immunotherapy by showing that treatment efficacy can be strongly shaped by immune responses originating not only within the tumor, but also in tumor-draining lymph nodes outside it.
Yumin Kim, a postdoctoral researcher in the KAIST Department of Biological Sciences, served as the first author of the study, with Professor Heung Kyu Lee serving as the corresponding author. Professor Ji Eun Oh from the KAIST Graduate School of Medical Science and Engineering also contributed to the research. The findings were published on July 10 in Science Immunology.
Paper title: The efficacy of immunotherapy in glioma requires distal B-cell responses in tumor-draining lymph nodes
DOI: 10.1126/sciimmunol.adz2494
Authors: Yumin Kim, In Kang, Byeong Hoon Kang, Won Hyung Park, Chae Won Kim, Hyun-Jin Kim, Jeongwoo La, Myoung Seung Kwon, Sang Hee Park, Seo Hyeon Im, Hyeon Cheol Kim, Keun Bon Ku, Minji Kim, and Ji Eun Oh from KAIST, with Heung Kyu Lee from KAIST as the corresponding author.
This research was supported by National Research Foundation of Korea grants RS-2023-NR077244 (to H.K.L.), RS-2024-00439735 (to H.K.L.), RS-2024-00411928 (to Y.K.), RS-2025-00517107 (to J.E.O.), and RS-2026-25509011 (to H.K.L.). This study was also supported by Samsung Science and Technology Foundation grants SSTF-BA1902-05 (to H.K.L.) and SSTF-BA2201-11 (to J.E.O.).
2026.07.20 View 1383 -
KAIST Enables DNA Synthesis Using Only Temperature Instead of Chemical Reagents
"Complex chemical processes are essential for making DNA." This long-held assumption in the field of biotechnology has been overturned by a Korean research team. A KAIST research team has developed the world's first foundational technology that enables the synthesis of desired DNA using only temperature. Using this technology, the team also demonstrated a "DNA temperature black box" that records temperature changes during shipping without electricity.
KAIST announced on the 7th of July that a research team led by Professor Yeongjae Choi of the Graduate School of Engineering Biology, in collaboration with ATG Lifetech Inc. (CEO Taehoon Ryu) and a research team led by Professor Hansol Choi from the Department of Life Science at Ewha Womans University, has developed this platform technology that synthesizes desired DNA sequences by controlling only temperature.
DNA is the "blueprint" that contains the genetic information of humans and all other living organisms. Scientists use custom-made DNA in various biotechnology applications, such as diagnosing diseases, developing new drugs, and creating microorganisms with new functions. Until now, however, each time one of the four bases that make up DNA—A, T, G, and C—was connected, chemical reagents had to be added and washed out repeatedly. As a result, costly automated DNA synthesis equipment and specialized research facilities were essential.
To overcome these limitations, the research team developed "hairpin DNA that reacts only at specific temperatures." This hairpin DNA is a special DNA structure that remains folded like a hairpin and unfolds only at a certain temperature. The team placed multiple types of hairpin DNA that operate at different temperatures into a single test tube and succeeded in synthesizing desired DNA step by step by changing only the temperature in the sequence.
This opens the way for synthesizing DNA with only a general temperature control device, without the need for complex reagent replacement or large-scale equipment.
As the technology advances, it is expected to greatly reduce the cost and time required to make DNA, lowering the entry barriers not only for synthetic biology and genetic research, but also for various bioindustries such as drug development and precision medicine.
To demonstrate the practical applicability of the technology, the research team also implemented a power-free "DNA temperature black box." This device is normally stored in a freeze-dried state and begins operating when a single drop of water is added just before use. It then automatically records—directly into a DNA sequence—when, how long, and in what order the temperature changes during shipping. In addition, when exposed to temperatures above a certain level, the device changes color, allowing abnormalities to be checked visually on the spot. It is expected to be used for the quality control of products for which cold-chain distribution is important, such as vaccines, biopharmaceuticals, cell therapies, and fresh foods.
KAIST researcher Jangho Choi and GIST doctoral student Jinho Kim participated in this research as co-first authors, and the research results were published in the international journal Nature Communications on July 2.
※ Paper title: Programmable one-pot polymerase-mediated DNA synthesis via temperature control
※ DOI: https://doi.org/10.1038/s41467-026-74890-4
※ Related Video: https://drive.google.com/file/d/1bUtzC83qIm1k-hNFKTb09yFPhfsD4iU-/view?usp=drive_lin
※ Authors: Jangho Choi (KAIST, co-first author), Jinho Kim (GIST, co-first author), Hansol Choi (Ewha Womans University, corresponding author), Yeongjae Choi (KAIST, corresponding author)
This research was supported by the Ministry of Science and ICT through the Future Promising Convergence Technology Pioneer Program, the Biofoundry-Based Technology Development Program, the Young Researcher Program, and the Global Basic Research Laboratory Program.
2026.07.07 View 1854 -
KAIST Develops AI That Reads Animal Behavior Like Language
An artificial intelligence model capable of reading and interpreting animal behavior like language has been developed by researchers at KAIST. The team created BehaVERT, an AI model that learns behavioral data in a manner similar to natural language and was able to independently identify social behavioral deficits in an autism mouse model, opening a new avenue for interpretable neuroscience.
KAIST (President Kwang-Hyung Lee) announced that a research team led by Professor Dae-Soo Kim from the Department of Brain and Cognitive Sciences has developed an AI model that interprets animal movements as a form of behavioral language.
The researchers transformed skeletal movements of mice into tokens, analogous to words in natural language, and trained a transformer-based model to learn behavioral meaning. The resulting model, named BehaVERT, successfully identified core social behavioral abnormalities in an autism mouse model without being provided any prior biological knowledge.
The study introduces a novel AI framework for analyzing animal behavior through language-based representations. Beyond simple behavior classification, the model demonstrates the ability to uncover biologically meaningful patterns and may serve as a foundation for next-generation behavioral foundation models applicable to drug discovery, psychiatric research, and behavioral genetics.
Inspired by the idea that animal behavior may possess structures similar to language, the researchers represented the positions of a mouse's nose, ears, spine, limbs, and tail as behavioral tokens and trained a BERT-based transformer architecture.
As a result, BehaVERT learned not only to classify behaviors but also to understand their contextual meaning over time, much like language models infer meaning from sequences of words.
The model achieved state-of-the-art performance across five international benchmark datasets covering social interaction, multi-animal behavior, three-dimensional motion analysis, and autism-related behavioral assessment.
Importantly, BehaVERT also provides interpretability, allowing researchers to visualize which behavioral cues influenced its decisions.
In experiments distinguishing Shank3B knockout autism-model mice from healthy controls, the AI consistently focused on oral-oral contact behavior. This finding aligns with previous biological studies showing that autism-model mice exhibit deficits in social interaction despite maintaining normal approach behavior.
In other words, the AI independently rediscovered a key biological characteristic solely from behavioral observations, without explicit biological instruction.
The researchers further found that the model's internal representation space organized behavioral features such as mobility, attention, and social engagement into structured patterns. This suggests that animal behavior, much like language, may possess an underlying semantic structure.
The study also highlights an unusual interdisciplinary achievement. The first author, Dr. Seungjae Shin, and other members of the research team were trained primarily in biology rather than artificial intelligence. By independently learning transformer architectures and deep learning techniques, they designed specialized models and training strategies tailored for behavioral analysis.
Professor Kim's laboratory has long pursued AI-driven behavioral analysis and previously developed AVATAR, a technology that reconstructs rodent behavior in virtual environments, leading to the founding of Actnova Inc.
"The project began with a simple question: Could animal movements contain a structure similar to language?" said Dr. Seungjae Shin, the first author of the study.
The team also adopted a self-supervised learning framework that enables AI to learn directly from behavioral data without manual annotations. Furthermore, a model trained on rat behavior successfully transferred to mouse behavior analysis, demonstrating the feasibility of a behavioral foundation model applicable across species.
"BehaVERT goes beyond behavior classification and enables the interpretation of behavioral meaning," said Professor Dae-Soo Kim. "We expect it to become a key research tool for discovering new insights in drug development, psychiatric disorders, behavioral genetics, and many other areas of life sciences."
The study was published on March 24, 2026, in the International Journal of Computer Vision (IJCV), one of the world's leading journals in computer vision.
Paper Information
• Title: BehaVERT: A Transformer-Based Motion Language Model for Decoding Behavioral Semantics in Mice
• Journal: International Journal of Computer Vision (IJCV)
• DOI: 10.1007/s11263-026-02834-y
Related Videos
• BehaVERT — Social Behavior Analysis Visualization (Investigation & Mount), https://youtu.be/JshCr-ZBQR0
• BehaVERT — Social Behavior Analysis Visualization (Investigation & Attack), https://youtu.be/p9RPhZM__Js
• BehaVERT — AI Discovers Core Social Behavioral Features in an Autism Mouse Model, https://youtu.be/D6zUyDu3t9I
Funding
This research was supported by the Mid-Career Researcher Program and the Brain Convergence Technology Development Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (MSIT), Republic of Korea.
2026.07.01 View 1633 -
KAIST Identifies New Therapeutic Target by Revealing How Cancer ‘Hijacks’ the Blueprint for Blood Vessel Development
Anti-angiogenic therapies targeting VEGF have been widely used in cancer treatment, yet their long-term efficacy remains limited. Tumor vascular endothelial cells (TECs) exhibit high adaptive plasticity, enabling them to resist treatment and sustain tumor growth, but the molecular mechanism underlying this plasticity has remained poorly understood.
KAIST, led by President Kwang Hyung Lee, announced that a joint research team led by Professor Inkyung Jung (Department of Biological Sciences), Professor Ji Min Lee (Graduate School of Medical Science and Engineering), and Professor Gou Young Koh (Institute for Basic Science) has now uncovered the answer. By integrating cross-cancer single-cell transcriptomic and epigenomic atlases across eight solid tumor types with multiomic profiles, including 3D chromatin contact maps, of human embryonic stem cell (hESC)-derived vascular endothelial cell differentiation, the team demonstrated that TECs reactivate a gene regulatory program normally confined to the late progenitor stage of vascular development. Much like reusing an old blueprint rather than drawing up a new one, tumors co-opt this pre-existing developmental program to fuel blood vessel growth.
The team’s integrative framework combined single-cell RNA-seq and ATAC-seq across multiple tumor types with H3K27ac ChIP-seq, Hi-C-based 3D chromatin mapping across a dense time series of hESC-to-EC differentiation. This approach resolved the EC-progenitor specific regulatory program that defines the shared pro-angiogenic program between late EC progenitors and TECs.
Within this framework, integrin receptor (ITGAV) emerged as a functional mediator specifically upregulated in both late EC progenitors and TECs. Cell-to-cell interaction analysis identified multiple key ligands from tumor micro enviroment (TME) that reactivate the progenitor-associated gene regulatory program. Pharmacologic inhibition attenuated endothelial migration, invasion, and tube formation in vitro, and significantly reduced tumor vascularization and growth in a colorectal cancer xenograft model in vivo.
Professor Inkyung Jung noted that this study reframes how we understand tumor angiogenesis: tumors do not invent new mechanisms, but exploit regulatory programs already embedded in normal vascular development. This insight offers a new conceptual basis for why anti-VEGF therapies face limitations, and points toward targeting the underlying regulatory architecture of endothelial plasticity as a complementary anti-angiogenic strategy.
The study was co-first authored by Dr. Andrew J. Lee, Dr. Sunwoo Min, Ph.D. student Su Chan Park; and Dr. Mei-Yu Qiu. Professors Inkyung Jung, Ji Min Lee, and Gou Young Koh served as corresponding authors. The findings were published on June 8 in Cancer Research [IF = 22.3].
※ Paper title: "A Co-opted Developmental Gene Regulatory Program in Endothelial Progenitors Promotes Tumor Angiogenic Phenotypes"
※ DOI: 10.1158/0008-5472.CAN-25-5094
※ Authors: Andrew J. Lee (KAIST, first author), Sunwoo Min (KAIST, co-first), Su Chan Park (KAIST, co-first), Mei-Yu Qiu (IBS, co-first), Gou Young Koh (IBS, co-corresponding), Ji Min Lee (KAIST, co-corresponding), Inkyung Jung (KAIST, corresponding)
This research was supported by the National Research Foundation of Korea and the Institute for Basic Science.
2026.07.01 View 1051 -
“Why are we depressed?” KAIST is identifying the cause of depression and uncovering clues for treatment
Major depressive disorder (MDD) is one of the most common psychiatric illnesses worldwide, but its molecular causes* have still not been clearly identified. A domestic research team has discovered that depression may not simply be caused by neuronal damage, but can also arise from the dysregulation of specific neural signaling pathways. In particular, they identified the molecular reason why elderly patients with depression do not respond to conventional antidepressants. This study suggests the possibility of therapeutic approaches using optogenetic technology to regulate neural signaling, and it provides clues for the development of new treatment strategies targeting the protein ‘Numb’ protein for elderly patients with depression.
*Molecular causes: explanations for the origin of a disease at the level of molecules, proteins, or genes in the brain.
KAIST (President Kwang Hyung Lee) announced on the 19th of August that a research team led by Distinguished Professor Won Do Heo of the Department of Biological Sciences at KAIST, in collaboration with forensic pathologist Minju Lee of the National Forensic Service (Director Bong Woo Lee) and Professor Seokhwi Kim of the Department of Pathology at Ajou University Medical Center (Director Sangwook Han), identified a new molecular mechanism for depression through RNA sequencing and the immunohistochemical analysis of brain tissue from patients who had committed suicide. Furthermore, they demonstrated in animal models that antidepressant effects can be restored by regulating the signaling pathway that induces neural recovery using optogenetic technology.
The research team focused on the hippocampus, the brain region responsible for memory and emotion, and in particular on the dentate gyrus (DG). The DG is the entry point of information into the hippocampus, playing a role in new memory formation, neurogenesis, and emotional regulation, and is closely linked with depression.
Using two representative mouse models for depression (the corticosterone stress model and the chronic unpredictable stress model), the team found that stress induced a striking increase in the signaling receptor FGFR1 (Fibroblast Growth Factor Receptor 1) in the DG. FGFR1 receives growth factor (FGF) signals and transmits growth and differentiation commands within cells.
Subsequently, using conditional knockout (cKO) mice in which the FGFR1 gene was deleted, the researchers revealed that the absence of FGFR1 made mice more vulnerable to stress and led them to exhibit depressive symptoms more quickly. This indicates that FGFR1 plays a critical role in proper neural regulation and stress resistance.
The team then developed an ‘optoFGFR1 system’ using optogenetics, enabling FGFR1 —essential for stress resistance—to be activated by light. They observed that activating FGFR1 in depression mouse models lacking FGFR1 restored antidepressant effects. In other words, they experimentally demonstrated that the activation of FGFR1 signaling alone could improve depressive behavior.
Surprisingly, however, in aged depression mouse models, the activation of FGFR1 signaling through the optoFGFR1 system did not yield antidepressant effects. Investigating further, the researchers found that in the aged brains, a protein called ‘Numb’ was excessively expressed and interfered with FGFR1 signaling.
Indeed, analysis of postmortem human brain tissue also showed the specific overexpression of Numb protein only in elderly patients with depression. When the researchers suppressed Numb using a gene regulatory tool (shRNA) while simultaneously activating FGFR1 signaling in mouse models, neurogenesis and behavior—previously unrecoverable—returned to normal even in aged depression models. This shows that the Numb protein acts as a “blocker” of FGFR1 signaling and is a key factor preventing the hippocampus from executing antidepressant mechanisms.
Distinguished Professor Won Do Heo of KAIST said, “This study is meaningful in that it revealed that depression may not only result from simple neuronal damage, but can also arise from the dysregulation of specific neural signaling pathways. In particular, we identified the molecular reason why antidepressants are less effective in elderly patients, and we expect this to provide a clue for the development of new therapeutic strategies targeting the Numb protein.”
He added, “Moreover, this interdisciplinary study, which combined KAIST’s expertise in neuroscience with the National Forensic Service’s forensic brain analysis technologies, is expected to serve as a bridge between basic research on psychiatric disorders and clinical applications.”
This study, led by first author Jongpil Shin, a PhD student in the Department of Biological Sciences at KAIST, was published on August 15, 2025, in the international journal Experimental & Molecular Medicine.
Paper title: “Dysregulation of FGFR1 signaling in the hippocampus facilitates depressive disorder”
DOI: https://doi.org/10.1038/s12276-025-01519-9
This research was supported by the Ministry of Science and ICT’s National Research Foundation of Korea through the ASTRA program and the Bio-Medical Technology Development project.
2025.08.19 View 4670 -
KAIST develops technology for selective RNA modification in living cells and animals
· A team led by Professor Won Do Heo from the Department of Biological Sciences, KAIST, has developed a pioneering technology that selectively acetylates specific RNA molecules in living cells and tissues.
· The platform uses RNA-targeting CRISPR tools in combination with RNA-modifying enzymes to chemically modify only the intended RNA.
· The method opens new possibilities for gene therapy by enabling precise control of disease-related RNA without affecting the rest of the transcriptome.
< Photo 1. (From left) Professor Won Do Heo and Jihwan Yu, a Ph.D. Candidate of the Department of Biological Sciences >
CRISPR-Cas13, a powerful RNA-targeting technology is gaining increasing attention as a next-generation gene therapy platform due to its precision and reduced side effects. Utilizing this system, researchers at KAIST have now developed the world’s first technology capable of selectively acetylating (chemically modifying) specific RNA molecules among countless transcripts within living cells. This breakthrough enables precise, programmable control of RNA function and is expected to open new avenues in RNA-based therapeutic development.
KAIST (President Kwang Hyung Lee) announced that a research team led by Professor Won Do Heo in the Department of Biological Sciences has recently developed a groundbreaking technology capable of selectively acetylating specific RNA molecules within the human body using the CRISPR-Cas13 system—an RNA-targeting platform gaining increasing attention in the fields of gene regulation and RNA-based therapeutics.
RNA molecules can undergo chemical modifications—the addition of specific chemical groups—which alter their function and behavior without changing the underlying nucleotide sequence. However, some of these modifications, a critical layer of post-transcriptional gene regulation, remain poorly understood. Among them, N4-acetylcytidine (ac4C) has been particularly enigmatic, with ongoing debate about its existence and function in human messenger RNA (mRNA), the RNA that encodes proteins.
To address this gap, the KAIST research team developed a targeted RNA acetylation system, named dCas13-eNAT10. This platform combines a catalytically inactive Cas13 enzyme (dCas13) that guides the system to specific RNA targets, with a hyperactive variant of the NAT10 enzyme (eNAT10), which performs RNA acetylation. This approach enables precise acetylation of only the desired RNA molecules among the vast pool of transcripts within the cell.
< Figure 1. Development of hyperactive variant eNAT10 through NAT10 protein engineering. By engineering the NAT10 protein, which performs RNA acetylation in human cells, based on its domain and structure, eNAT10 was developed, showing approximately a 3-fold increase in RNA acetylation activity compared to the wild-type enzyme. >
Using this system, the researchers demonstrated that guide RNAs could direct the dCas13-eNAT10 complex to acetylate specific RNA targets, and acetylation significantly increased protein expression from the modified mRNA. Moreover, the study revealed, for the first time, that RNA acetylation plays a role in intracellular RNA localization, facilitating the export of RNA from the nucleus to the cytoplasm—a critical step in gene expression regulation.
To validate its therapeutic potential, the team successfully delivered the targeted RNA acetylation system into the livers of live mice using adeno-associated virus (AAV), a commonly used gene therapy vector. This marks the first demonstration of in vivo RNA modification, extending the applicability of RNA chemical modification tools from cell culture models to living organisms.
< Figure 2. Acetylation of various RNA in cells using dCas13-eNAT10 fusion protein. Utilizing the CRISPR-Cas13 system, which can precisely target specific RNA through guide RNA, a dCas13-eNAT10 fusion protein was created, demonstrating its ability to specifically acetylate various endogenous RNA at different locations within cells. >
Professor Won Do Heo, who previously developed COVID-19 treatment technology using RNA gene scissors and technology to activate RNA gene scissors with light, stated, "Existing RNA chemical modification research faced difficulties in controlling specificity, temporality, and spatiality. However, this new technology allows selective acetylation of desired RNA, opening the door for accurate and detailed research into the functions of RNA acetylation." He added, "The RNA chemical modification technology developed in this study can be widely used as an RNA-based therapeutic agent and a tool for regulating RNA functions in living organisms in the future."
< Figure 3. In vivo delivery of targeted RNA acetylation system. The targeted RNA acetylation system was encoded in an AAV vector, commonly used in gene therapy, and delivered intravenously to adult mice, showing that target RNA in liver tissue was specifically acetylated according to the guide RNA. >
This research, with Ph.D. candidate Jihwan Yu from the Department of Biological Sciences at KAIST as the first author, was published in the journal Nature Chemical Biology on June 2, 2025. (Title: Programmable RNA acetylation with CRISPR-Cas13, Impact factor: 12.9, DOI: https://doi.org/10.1038/s41589-025-01922-3)
This research was supported by the Samsung Future Technology Foundation and the Bio & Medical Technology Development Program of the National Research Foundation of Korea.
2025.06.10 View 7855 -
A 10-Month Journey of Tiny Flaps Completed: A Special Family Returns to KAIST Duck Pond
On the morning of June 9, 2025, gentle activity stirred early around the KAIST campus duck pond. It was the day a special family of ducks—and two goslings—were to be released back into the pond after spending a month in a temporary shelter. One by one, the ducklings cautiously emerged from their box, waddling toward the water's edge and scanning their surroundings, followed closely by their mother.
< The landscape manager from the KAIST Facilities Team releases the ducks and goslings. >
The mother duck, once a rescued loner who couldn’t integrate with the flock, returned triumphantly as the head of a new family—caring for both ducklings and goslings. Students and faculty looked on quietly, welcoming them back and reflecting on their remarkable 10-month journey.
The story began in July 2024, as a student filed a report of spotting two ducklings wandering near the pond without a mother. Based on their soft down, flat beaks, and lack of fear around humans, it was presumed they had been abandoned. Professor Won Do Heo of the Department of Biological Sciences—affectionately known as the “Goose Dad”—and the KAIST Facilities Team quickly stepped in to rescue them. After about a month of care, the ducklings were released back into the pond.
< On June 9, the day of the release, KAIST President Kwang-Hyung Lee (left), the former “Goose Dad,” and Professor Won Do Heo (right), the current “Goose Dad,” watched the flock as they freely wobbled about. >
At first, the ducklings seemed to adapt, but they started distancing themselves from the established goose flock. One eventually disappeared, and the remaining duckling was found injured by the pond during winter. Although KAIST typically avoids making human interference in the natural ecosystem, an exception was made to save the young duck’s life. It was put under the care of Professor Heo and the Facilities Team to regain its health within a month.
In the spring, the healed duck began laying eggs. Professor Heo supported the process by adjusting its diet, avoiding further intervention. On Children’s Day, May 5, the duck’s eggs hatched. The once-isolated duck had become a mother. Ten days later, on May 15, four goslings also hatched from the resident goose flock. With new life flourishing, the pond was more vibrant than ever.
< Rescued baby goslings near the pond, alongside the duck family that took them in. The mother duck—once a vulnerable duckling herself—had grown strong enough to care for others in need. >
But just days later, the mother goose disappeared, and two goslings—still unable to swim—were found shivering by the pond. Dahyeon Byeon, a student from Seoul National University who came for a visit on that day, reported this upon sighting, prompting another rescue. The vulnerable goslings were brought to the shelter to stay with the duck family.
Initially, the interspecies cohabitation was uneasy. But the mother duck did not reject the goslings. Slowly, they began to eat and sleep together, forming a new kind of family. After a month, they were released together into the pond—and to everyone’s surprise, the existing goose flock accepted both the goslings and the duck family.
< A peaceful moment for the duck family. The baby goslings naturally followed the mother duck. >
It took ten months for this family to return. From abandonment and injury to healing, birth, and unexpected bonds, this was more than a story of survival. It was a journey of transformation. The duck family’s ten-month saga is a quiet miracle—written in small moments of crisis, care, and connection—and a lasting memory on the KAIST campus.
< The resident goose flock at KAIST’s pond naturally accepted the returning duck and goslings as part of their group. >
2025.06.10 View 7867 -
KAIST-UIUC researchers develop a treatment platform to disable the ‘biofilm’ shield of superbugs
< (From left) Ph.D. Candidate Joo Hun Lee (co-author), Professor Hyunjoon Kong (co-corresponding author) and Postdoctoral Researcher Yujin Ahn (co-first author) from the Department of Chemical and Biomolecular Engineering of the University of Illinois at Urbana-Champaign and Ju Yeon Chung (co-first author) from the Integrated Master's and Doctoral Program, and Professor Hyun Jung Chung (co-corresponding author) from the Department of Biological Sciences of KAIST >
A major cause of hospital-acquired infections, the super bacteria Methicillin-resistant Staphylococcus aureus (MRSA), not only exhibits strong resistance to existing antibiotics but also forms a dense biofilm that blocks the effects of external treatments. To meet this challenge, KAIST researchers, in collaboration with an international team, successfully developed a platform that utilizes microbubbles to deliver gene-targeted nanoparticles capable of break ing down the biofilms, offering an innovative solution for treating infections resistant to conventional antibiotics.
KAIST (represented by President Kwang Hyung Lee) announced on May 29 that a research team led by Professor Hyun Jung Chung from the Department of Biological Sciences, in collaboration with Professor Hyunjoon Kong's team at the University of Illinois, has developed a microbubble-based nano-gene delivery platform (BTN MB) that precisely delivers gene suppressors into bacteria to effectively remove biofilms formed by MRSA.
The research team first designed short DNA oligonucleotides that simultaneously suppress three major MRSA genes, related to—biofilm formation (icaA), cell division (ftsZ), and antibiotic resistance (mecA)—and engineered nanoparticles (BTN) to effectively deliver them into the bacteria.
< Figure 1. Effective biofilm treatment using biofilm-targeting nanoparticles controlled by microbubbler system. Schematic illustration of BTN delivery with microbubbles (MB), enabling effective permeation of ASOs targeting bacterial genes within biofilms infecting skin wounds. Gene silencing of targets involved in biofilm formation, bacterial proliferation, and antibiotic resistance leads to effective biofilm removal and antibacterial efficacy in vivo. >
In addition, microbubbles (MB) were used to increase the permeability of the microbial membrane, specifically the biofilm formed by MRSA. By combining these two technologies, the team implemented a dual-strike strategy that fundamentally blocks bacterial growth and prevents resistance acquisition.
This treatment system operates in two stages. First, the MBs induce pressure changes within the bacterial biofilm, allowing the BTNs to penetrate. Then, the BTNs slip through the gaps in the biofilm and enter the bacteria, delivering the gene suppressors precisely. This leads to gene regulation within MRSA, simultaneously blocking biofilm regeneration, cell proliferation, and antibiotic resistance expression.
In experiments conducted in a porcine skin model and a mouse wound model infected with MRSA biofilm, the BTN MB treatment group showed a significant reduction in biofilm thickness, as well as remarkable decreases in bacterial count and inflammatory responses.
< Figure 2. (a) Schematic illustration on the evaluation of treatment efficacy of BTN-MB gene therapy. (b) Reduction in MRSA biofilm mass via simultaneous inhibition of multiple genes. (c, d) Antibacterial efficacy of BTN-MB over time in a porcine skin infection biofilm model. (e) Schematic of the experimental setup to verify antibacterial efficacy in a mouse skin wound infection model. (f) Wound healing effects in mice. (g) Antibacterial effects at the wound site. (h) Histological analysis results. >
These results are difficult to achieve with conventional antibiotic monotherapy and demonstrate the potential for treating a wide range of resistant bacterial infections.
Professor Hyun Jung Chung of KAIST, who led the research, stated, “This study presents a new therapeutic solution that combines nanotechnology, gene suppression, and physical delivery strategies to address superbug infections that existing antibiotics cannot resolve. We will continue our research with the aim of expanding its application to systemic infections and various other infectious diseases.”
< (From left) Ju Yeon Chung from the Integrated Master's and Doctoral Program, and Professor Hyun Jung Chung from the Department of Biological Sciences >
The study was co-first authored by Ju Yeon Chung, a graduate student in the Department of Biological Sciences at KAIST, and Dr. Yujin Ahn from the University of Illinois. The study was published online on May 19 in the journal, Advanced Functional Materials.
※ Paper Title: Microbubble-Controlled Delivery of Biofilm-Targeting Nanoparticles to Treat MRSA Infection ※ DOI: https://doi.org/10.1002/adfm.202508291
This study was supported by the National Research Foundation and the Ministry of Health and Welfare, Republic of Korea; and the National Science Foundation and National Institutes of Health, USA.
2025.05.29 View 11381 -
Decoding Fear: KAIST Identifies An Affective Brain Circuit Crucial for Fear Memory Formation by Non-nociceptive Threat Stimulus
Fear memories can form in the brain following exposure to threatening situations such as natural disasters, accidents, or violence. When these memories become excessive or distorted, they can lead to severe mental health disorders, including post-traumatic stress disorder (PTSD), anxiety disorders, and depression. However, the mechanisms underlying fear memory formation triggered by affective pain rather than direct physical pain have remained largely unexplored – until now.
A KAIST research team has identified, for the first time, a brain circuit specifically responsible for forming fear memories in the absence of physical pain, marking a significant advance in understanding how psychological distress is processed and drives fear memory formation in the brain. This discovery opens the door to the development of targeted treatments for trauma-related conditions by addressing the underlying neural pathways.
< Photo 1. (from left) Professor Jin-Hee Han, Dr. Junho Han and Ph.D. Candidate Boin Suh of the Department of Biological Sciences >
KAIST (President Kwang-Hyung Lee) announced on May 15th that the research team led by Professor Jin-Hee Han in the Department of Biological Sciences has identified the pIC-PBN circuit*, a key neural pathway involved in forming fear memories triggered by psychological threats in the absence of sensory pain. This groundbreaking work was conducted through experiments with mice.*pIC–PBN circuit: A newly identified descending neural pathway from the posterior insular cortex (pIC) to the parabrachial nucleus (PBN), specialized for transmitting psychological threat information.
Traditionally, the lateral parabrachial nucleus (PBN) has been recognized as a critical part of the ascending pain pathway, receiving pain signals from the spinal cord. However, this study reveals a previously unknown role for the PBN in processing fear induced by non-painful psychological stimuli, fundamentally changing our understanding of its function in the brain.
This work is considered the first experimental evidence that 'emotional distress' and 'physical pain' are processed through different neural circuits to form fear memories, making it a significant contribution to the field of neuroscience. It clearly demonstrates the existence of a dedicated pathway (pIC-PBN) for transmitting emotional distress.
The study's first author, Dr. Junho Han, shared the personal motivation behind this research: “Our dog, Lego, is afraid of motorcycles. He never actually crashed into one, but ever since having a traumatizing event of having a motorbike almost run into him, just hearing the sound now triggers a fearful response. Humans react similarly – even if you didn’t have a personal experience of being involved in an accident, a near-miss or exposure to alarming media can create lasting fear memories, which may eventually lead to PTSD.”
He continued, “Until now, fear memory research has mainly relied on experimental models involving physical pain. However, much of real-world human fears arise from psychological threats, rather than from direct physical harm. Despite this, little was known about the brain circuits responsible for processing these psychological threats that can drive fear memory formation.”
To investigate this, the research team developed a novel fear conditioning model that utilizes visual threat stimuli instead of electrical shocks. In this model, mice were exposed to a rapidly expanding visual disk on a ceiling screen, simulating the threat of an approaching predator. This approach allowed the team to demonstrate that fear memories can form in response to a non-nociceptive, psychological threat alone, without the need for physical pain.
< Figure 1. Artificial activation of the posterior insular cortex (pIC) to lateral parabrachial nucleus (PBN) neural circuit induces anxiety-like behaviors and fear memory formation in mice. >
Using advanced chemogenetic and optogenetic techniques, the team precisely controlled neuronal activity, revealing that the lateral parabrachial nucleus (PBN) is essential to form fear memories in response to visual threats. They further traced the origin of these signals to the posterior insular cortex (pIC), a region known to process negative emotions and pain, confirming a direct connection between the two areas.
The study also showed that inhibiting the pIC–PBN circuit significantly reduced fear memory formation in response to visual threats, without affecting innate fear responses or physical pain-based learning. Conversely, artificially activating this circuit alone was sufficient to drive fear memory formation, confirming its role as a key pathway for processing psychological threat information.
< Figure 2. Schematic diagram of brain neural circuits transmitting emotional & physical pain threat signals. Visual threat stimuli do not involve physical pain but can create an anxious state and form fear memory through the affective pain signaling pathway. >
Professor Jin-Hee Han commented, “This study lays an important foundation for understanding how emotional distress-based mental disorders, such as PTSD, panic disorder, and anxiety disorder, develop, and opens new possibilities for targeted treatment approaches.”
The findings, authored by Dr. Junho Han (first author), Ph.D. candidate Boin Suh (second author), and Dr. Jin-Hee Han (corresponding author) of the Department of Biological Sciences, were published online in the international journal Science Advances on May 9, 2025.※ Paper Title: A top-down insular cortex circuit crucial for non-nociceptive fear learning. Science Advances (https://doi.org/10.1101/2024.10.14.618356)※ Author Information: Junho Han (first author), Boin Suh (second author), and Jin-Hee Han (corresponding author)
This research was supported by grants from the National Research Foundation of Korea (NRF-2022M3E5E8081183 and NRF-2017M3C7A1031322).
2025.05.15 View 11452