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KAIST Develops Retinal Therapy to Restore Lost Vision
Vision is one of the most crucial human senses, yet over 300 million people worldwide are at risk of vision loss due to various retinal diseases. While recent advancements in retinal disease treatments have successfully slowed disease progression, no effective therapy has been developed to restore already lost vision—until now. KAIST researchers have successfully developed a novel drug to restore vision.
< Photo 1. (From left) Ph.D. candidate Museong Kim, Professor Jin Woo Kim, and Dr. Eun Jung Lee of KAIST Department of Biological Sciences >
KAIST (represented by President Kwang Hyung Lee) announced on the 30th of March that a research team led by Professor Jin Woo Kim from the Department of Biological Sciences has developed a treatment method that restores vision through retinal nerve regeneration.
The research team successfully induced retinal regeneration and vision recovery in a disease-model mouse by administering a compound that blocks the PROX1 (prospero homeobox 1) protein, which suppresses retinal regeneration. Furthermore, the effect lasted for more than six months.
This study marks the first successful induction of long-term neural regeneration in mammalian retinas, offering new hope to patients with degenerative retinal diseases who previously had no treatment options.
As the global population continues to age, the number of retinal disease patients is steadily increasing. However, no treatments exist to restore damaged retinas and vision. The primary reason for this is the mammalian retina's inability to regenerate once damaged.
Studies on cold-blooded animals, such as fish—known for their robust retinal regeneration—have shown that retinal injuries trigger Müller glia cells to dedifferentiate into retinal progenitor cells, which then generate new neurons. However, in mammals, this process is impaired, leading to permanent retinal damage.
< Figure 1. Schematic diagram of the mechanism of retinal regeneration through inhibition of PROX1 migration. PROX1 protein secreted from retinal damaged retinal neurons transfers to Müllerglia and inhibits dedifferentiation into neural progenitor cells and neural regeneration. When PROX1 is captured outside the cells by an antibody against PROX1 and its transfer to Müllerglia is interfered, dedifferentiation of Müllerglia cells and retinal regeneration processes are resumed, restoring visual function. >
Through this study, the research team identified the PROX1 protein as a key inhibitor of Müller glia dedifferentiation in mammals. PROX1 is a protein found in neurons of the retina, hippocampus, and spinal cord, where it suppresses neural stem cell proliferation and promotes differentiation into neurons.
The researchers discovered that PROX1 accumulates in damaged mouse retinal Müller glia, but is absent in the highly regenerative Müller glia of fish. Furthermore, they demonstrated that the PROX1 found in Müller glia is not synthesized internally but rather taken up from surrounding neurons, which fail to degrade and instead secrete the protein.
Based on this finding, the team developed a method to restore Müller glia’s regenerative ability by eliminating extracellular PROX1 before it reaches these cells.
< Figure 2. Retinal regeneration and visual recovery in a retinitis pigmentosa model mouse through Anti-PROX1 gene therapy. After administration of adeno-associated virus expressing PROX1 neutralizing antibodies (AAV2-Anti-PROX1) to the eyes of RP1 retinitis pigmentosa model mice with vision loss, the photoreceptor cell layer of the retina is restored (A) and vision is restored (B). >
This approach involves using an antibody that binds to PROX1, developed by Celliaz Inc., a biotech startup founded by Professor Jin Woo Kim’s research lab. When administered to disease-model mouse retinas, this antibody significantly promoted neural regeneration. Additionally, when delivered, the antibody gene to the retinas of retinitis pigmentosa disease model mice, it enabled sustained retinal regeneration and vision restoration for over six months.
The retinal regeneration-inducing therapy is currently being developed by Celliaz Inc. for application in various degenerative retinal diseases that currently lack effective treatments. The company aims to begin clinical trials by 2028.
This study was co-authored by Dr. Eun Jung Lee of Celliaz Inc. and Museong Kim, a Ph.D. candidate at KAIST, as joint first authors. The findings were published online on March 26 in the international journal Nature Communications. (Paper Title: Restoration of retinal regenerative potential of Müller glia by disrupting intercellular Prox1 transfer | DOI: 10.1038/s41467-025-58290-8)
Dr. Eun Jung Lee stated, "We are about completing the optimization of the PROX1-neutralizing antibody (CLZ001) and move to preclinical studies before administering it to retinal disease patients. Our goal is to provide a solution for patients at risk of blindness who currently lack proper treatment options."
This research was supported by research funds from Korean National Research Foundation (NRF) and the Korea Drug Development Foundation (KDDF).
2025.03.31 View 1057 -
KAIST provides a comprehensive resource on microbial cell factories for sustainable chemical production
In silico analysis of five industrial microorganisms identifies optimal strains and metabolic engineering strategies for producing 235 valuable chemicals
Climate change and the depletion of fossil fuels have raised the global need for sustainable chemical production. In response to these environmental challenges, microbial cell factories are gaining attention as eco-friendly platforms for producing chemicals using renewable resources, while metabolic engineering technologies to enhance these cell factories are becoming crucial tools for maximizing production efficiency. However, difficulties in selecting suitable microbial strains and optimizing complex metabolic pathways continue to pose significant obstacles to practical industrial applications.
KAIST (President Kwang-Hyung Lee) announced on 27th of March that Distinguished Professor Sang Yup Lee’s research team in the Department of Chemical and Biomolecular Engineering comprehensively evaluated the production capabilities of various industrial microbial cell factories using in silico simulations and, based on these findings, identified the most suitable microbial strains for producing specific chemicals as well as optimal metabolic engineering strategies.
Previously, researchers attempted to determine the best strains and efficient metabolic engineering strategies among numerous microbial candidates through extensive biological experiments and meticulous verification processes. However, this approach required substantial time and costs. Recently, the introduction of genome-scale metabolic models (GEMs), which reconstruct the metabolic networks within an organism based on its entire genome information, has enabled systematic analysis of metabolic fluxes via computer simulations. This development offers a new way to overcome limitations of conventional experimental approaches, revolutionizing both strain selection and metabolic pathway design.
Accordingly, Professor Lee’s team at the Department of Chemical and Biomolecular Engineering, KAIST, evaluated the production capabilities of five representative industrial microorganisms—Escherichia coli, Saccharomyces cerevisiae, Bacillus subtilis, Corynebacterium glutamicum, and Pseudomonas putida—for 235 bio-based chemicals. Using GEMs, the researchers calculated both the maximum theoretical yields and the maximum achievable yields under industrial conditions for each chemical, thereby establishing criteria to identify the most suitable strains for each target compound.
< Figure 1. Outline of the strategy for improving microbial cell factories using a genome-scale metabolic model (GEM) >
The team specifically proposed strategies such as introducing heterologous enzyme reactions derived from other organisms and exchanging cofactors used by microbes to expand metabolic pathways. These strategies were shown to increase yields beyond the innate metabolic capacities of the microorganisms, resulting in higher production of industrially important chemicals such as mevalonic acid, propanol, fatty acids, and isoprenoids.
Moreover, by applying a computational approach to analyze metabolic fluxes in silico, the researchers suggested strategies for improving microbial strains to maximize the production of various chemicals. They quantitatively identified the relationships between specific enzyme reactions and target chemical production, as well as the relationships between enzymes and metabolites, determining which enzyme reactions should be up- or down-regulated. Through this, the team presented strategies not only to achieve high theoretical yields but also to maximize actual production capacities.
< Figure 2. Comparison of production routes and maximum yields of useful chemicals using representative industrial microorganisms >
Dr. Gi Bae Kim, the first author of this paper from the KAIST BioProcess Engineering Research Center, explained, “By introducing metabolic pathways derived from other organisms and exchanging cofactors, it is possible to design new microbial cell factories that surpass existing limitations. The strategies presented in this study will play a pivotal role in making microbial-based production processes more economical and efficient.” In addition, Distinguished Professor Sang Yup Lee noted, “This research serves as a key resource in the field of systems metabolic engineering, reducing difficulties in strain selection and pathway design, and enabling more efficient development of microbial cell factories. We expect it to greatly contribute to the future development of technologies for producing various eco-friendly chemicals, such as biofuels, bioplastics, and functional food materials.”
This research was conducted with the support from the Development of platform technologies of microbial cell factories for the next-generation biorefineries project and Development of advanced synthetic biology source technologies for leading the biomanufacturing industry project (Project Leader: Distinguished Professor Sang Yup Lee, KAIST) from National Research Foundation supported by the Korean Ministry of Science and ICT.
2025.03.27 View 515 -
KAIST Develops Eco-Friendly, Nylon-Like Plastic Using Microorganisms
Poly(ester amide) amide is a next-generation material that combines the advantages of PET (polyester) and nylon (polyamide), two widely used plastics. However, it could only be produced from fossil fuels, which posed environmental concerns. Using microorganisms, KAIST researchers have successfully developed a new bio-based plastic to replace conventional plastic.
KAIST (represented by President Kwang Hyung Lee) announced on the 20th of March that a research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering has developed microbial strains through systems metabolic engineering to produce various eco-friendly, bio-based poly(ester amide)s. The team collaborated with researchers from the Korea Research Institute of Chemical Technology (KRICT, President Young-Kook Lee) to analyze and confirm the properties of the resulting plastic.
Professor Sang Yup Lee’s research team designed new metabolic pathways that do not naturally exist in microorganisms, and developed a platform microbial strain capable of producing nine different types of poly(ester amide)s, including poly(3-hydroxybutyrate-ran-3-aminopropionate) and poly(3-hydroxybutyrate-ran-4-aminobutyrate).
Using glucose derived from abundant biomass sources such as waste wood and weeds, the team successfully produced poly(ester amide)s in an eco-friendly manner. The researchers also confirmed the potential for industrial-scale production by demonstrating high production efficiency (54.57 g/L) using fed-batch fermentation of the engineered strain.
In collaboration with researchers Haemin Jeong and Jihoon Shin from KRICT, the KAIST team analyzed the properties of the bio-based plastic and found that it exhibited characteristics similar to high-density polyethylene (HDPE). This means the new plastic is not only eco-friendly but also strong and durable enough to replace conventional plastics.
The engineered strains and strategies developed in this study are expected to be useful not only for producing various poly(ester amide)s but also for constructing metabolic pathways for the biosynthesis of other types of polymers.
Professor Sang Yup Lee stated, “This study is the first to demonstrate the possibility of producing poly(ester amide)s (plastics) through a renewable bio-based chemical process rather than relying on the petroleum-based chemical industry. We plan to further enhance the production yield and efficiency through continued research.”
The study was published online on March 17 in the international journal Nature Chemical Biology.
·Title: Biosynthesis of poly(ester amide)s in engineered Escherichia coli
·DOI: 10.1038/s41589-025-01842-2
·Authors: A total of seven authors including Tong Un Chae (KAIST, first author), So Young Choi (KAIST, second author), Da-Hee Ahn (KAIST, third author), Woo Dae Jang (KAIST, fourth author), Haemin Jeong (KRICT, fifth author), Jihoon Shin (KRICT, sixth author), and Sang Yup Lee (KAIST, corresponding author).
This research was supported by the Ministry of Science and ICT (MSIT) under the Eco-Friendly Chemical Technology Development Project as part of the "Next-Generation Biorefinery Technology Development to Lead the Bio-Chemical Industry" initiative (project led by Distinguished Professor Sang Yup Lee at KAIST).
2025.03.24 View 1057 -
KAIST Develops World-Leading Ammonia Catalyst for Hydrogen Economy
Hydrogen production using renewable energy is a key technology for eco-friendly energy and chemical production. However, storing and transporting hydrogen remains a challenge. To address this, researchers worldwide are investigating methods to store hydrogen in the form of ammonia (NH₃), which is carbon-free and easier to liquify. A research team at KAIST has successfully developed a high-performance catalyst that enables ammonia synthesis at very low temperatures and pressures without energy loss.
KAIST (represented by President Kwang Hyung Lee) announced on the 11th of March that a research team led by Professor Minkee Choi from the Department of Chemical and Biomolecular Engineering has developed an innovative catalytic system that significantly enhances ammonia production while drastically reducing energy consumption and CO₂ emissions.
< (From left) Baek Ye-jun, Ph.D. candidate in the Department of Biochemical Engineering, Professor Choi Min-ki >
Currently, ammonia is produced using the Haber-Bosch process, a technology over a century old that relies on iron (Fe)-based catalysts. This method requires extreme conditions—temperatures above 500°C and pressures exceeding 100 atmospheres—resulting in enormous energy consumption and contributing significantly to global CO₂ emissions. Additionally, ammonia is primarily produced in large-scale industrial plants, leading to high distribution costs.
As an alternative, there is growing interest in an eco-friendly process that synthesizes ammonia using green hydrogen—produced via water electrolysis—under mild conditions (300°C, 10 atmospheres). However, developing catalysts that can achieve high ammonia productivity at such low temperatures and pressures is essential, as current technologies struggle to maintain efficiency under these conditions.
The research team developed a novel catalyst by incorporating ruthenium (Ru) nanoparticles and highly basic barium oxide (BaO) particles onto a conductive carbon surface, allowing it to function like a chemical capacitor*.
*Capacitor: A device that stores electrical energy by separating positive and negative charges.
During ammonia synthesis, hydrogen molecules (H₂) first dissociate into hydrogen atoms (H) on the ruthenium catalyst. These hydrogen atoms are further split into protons (H⁺) and electrons (e⁻). The study revealed that the acidic protons are stored in the strongly basic BaO, while the remaining electrons are separated and stored in ruthenium and carbon.
This unique chemical capacitor effect significantly enhances the ruthenium catalyst's electron density, accelerating nitrogen (N₂) dissociation—the rate-limiting step of ammonia synthesis—thereby dramatically increasing catalytic activity.
Furthermore, the team discovered that optimizing the nanostructure of the carbon material further boosts the electron density of ruthenium, maximizing catalytic performance. As a result, the new catalyst demonstrated over seven times higher ammonia synthesis performance compared to state-of-the-art catalysts under mild conditions (300°C, 10 atm).
< Schematic diagram showing the mechanism of ruthenium catalyst activity enhancement by barium oxide cocatalyst >
Professor Minkee Choi stated, “This research has garnered significant attention for demonstrating that catalytic activity can be greatly enhanced by controlling electron transfer within a thermal catalytic reaction system, not just in electrochemical processes.”
He further explained, “Our findings confirm that high-performance catalysts can enable efficient ammonia synthesis under low-temperature and low-pressure conditions. This could shift ammonia production from centralized, large-scale industrial plants to decentralized, small-scale production, making the hydrogen economy more sustainable and flexible.”
The study was led by Professor Minkee Choi as corresponding author and Yaejun Baik, a Ph.D. candidate, as first author. The research findings were published in Nature Catalysis on February 24.
(Paper title: “Electron and proton storage on separate Ru and BaO domains mediated by conductive low-work-function carbon to accelerate ammonia synthesis,” https://doi.org/10.1038/s41929-025-01302-z)
This research was supported by the Korea Institute of Energy Research and the National Research Foundation of Korea.
2025.03.11 View 798 -
KAIST perfectly reproduces Joseon-era Irworobongdo without pigments
Typically, chemical pigments that absorb specific wavelengths of light within the visible spectrum are required to produce colors. However, KAIST researchers have successfully reproduced the Joseon-era Irworobongdo [일월오봉도] painting using ultra-precise color graphics without any chemical pigments, allowing for the permanent and eco-friendly preservation of color graphics without fading or discoloration.
< (From left) Chaerim Son, a graduate of the Department of Biochemical Engineering (lead author), Seong Kyeong Nam, a graduate of the PhD program, Jiwoo Lee, a PhD student, and Professor Shin-Hyun Kim >
KAIST (represented by President Kwang Hyung Lee) announced on the 26th of February that a research team led by Professor Shinhyun Kim from the Department of Biological and Chemical Engineering had developed a technology that enables high-resolution color graphics without using any chemical pigments by employing hemisphere-shaped microstructures.
Morpho butterflies that are brilliant blue in color or Panther chameleons that change skin color exhibit coloration without chemical pigments, as ordered nanostructures within a material reflect visible light through optical interference. Since structural colors arise from physical structures rather than chemical substances, a single material can produce a wide range of colors.
However, the artificial implementation of structural coloration is highly challenging due to the complexity of creating ordered nanostructures. Additionally, it is difficult to produce a variety of colors and to pattern them precisely into complex designs.
< Figure 1. Principle of structural color expression using micro-hemispheres (left) and method of forming micro-hemisphere patterns based on photolithography (right) >
Professor Kim’s team overcame these challenges by using smooth-surfaced hemispherical microstructures instead of ordered nanostructures, enabling the high-precision patterning of diverse structural colors.
When light enters the inverted hemispherical microstructures, the portion of light entering from the sides undergoes total internal reflection along the curved surface, creating retroreflection. When the hemisphere diameter is approximately 10 micrometers (about one-tenth the thickness of a human hair), light traveling along different reflection paths interferes within the visible spectrum, producing structural coloration.
< Figure 2. “Irworobongdo”, the Painting of the Sun, Moon, and the Five Peaks, reproduced in fingernail size without pigment using approximately 200,000 micro-hemispheres >
The structural color can be tuned by adjusting the size of the hemispheres. By arranging hemispheres of varying sizes, much like mixing paints on a palette, an infinite range of colors can be generated.
To precisely pattern microscale hemispheres of different sizes, the research team employed photolithography* using positive photoresists** commonly used in semiconductor processing. They first patterned photoresists into micropillar structures, then induced reflow*** by heating the material, forming hemispherical microstructures.
*Photolithography: A technique used in semiconductor fabrication to pattern microscale structures.
**Positive photoresist: A photosensitive polymer that dissolves more easily in a developer solution after exposure to ultraviolet light.
***Reflow: A process in which a polymer material softens and reshapes into a curved structure when heated.
This method enables the formation of hemisphere-shaped microstructures with the desired sizes and colors in a single-step fabrication process. It also allows for the reproduction of arbitrary color graphics using a single material without any pigments.
The ultra-precise color graphics created with this technique can exhibit color variations depending on the angle of incident light or the viewing perspective. The pattern appears colored from one direction while remaining transparent from the opposite side, exhibiting a Janus effect. These structural color graphics achieve resolution comparable to cutting-edge LED displays, allowing complex color images to be captured within a fingernail-sized area and projected onto large screens.
< Figure 3. “Irworobongdo” that displays different shades depending on the angle of light and viewing direction >
Professor Shinhyun Kim, who led the research, stated, “Our newly developed pigment-free color graphics technology can serve as an innovative method for artistic expression, merging art with advanced materials. Additionally, it holds broad application potential in optical devices and sensors, anti-counterfeiting materials, aesthetic photocard printing, and many other fields.”
This research, with KAIST researcher Chaerim Son as the first author, was published in the prestigious materials science journal Advanced Materials on February 5.
(Paper title: “Retroreflective Multichrome Microdome Arrays Created by Single-Step Reflow”, DOI: 10.1002/adma.202413143 )
< Figure 4. Famous paintings reproduced without pigment: “Impression, Sunrise” (left), “Girl with a Pearl Earring” (right) >
The study was supported by the National Research Foundation of Korea through the Pioneer Converging Technology R&D Program and the Mid-Career Researcher Program.
2025.02.26 View 1117 -
KAIST Discovers Molecular Switch that Reverses Cancerous Transformation at the Critical Moment of Transition
< (From left) PhD student Seoyoon D. Jeong, (bottom) Professor Kwang-Hyun Cho, (top) Dr. Dongkwan Shin, Dr. Jeong-Ryeol Gong >
Professor Kwang-Hyun Cho’s research team has recently been highlighted for their work on developing an original technology for cancer reversal treatment that does not kill cancer cells but only changes their characteristics to reverse them to a state similar to normal cells. This time, they have succeeded in revealing for the first time that a molecular switch that can induce cancer reversal at the moment when normal cells change into cancer cells is hidden in the genetic network.
KAIST (President Kwang-Hyung Lee) announced on the 5th of February that Professor Kwang-Hyun Cho's research team of the Department of Bio and Brain Engineering has succeeded in developing a fundamental technology to capture the critical transition phenomenon at the moment when normal cells change into cancer cells and analyze it to discover a molecular switch that can revert cancer cells back into normal cells.
A critical transition is a phenomenon in which a sudden change in state occurs at a specific point in time, like water changing into steam at 100℃. This critical transition phenomenon also occurs in the process in which normal cells change into cancer cells at a specific point in time due to the accumulation of genetic and epigenetic changes.
The research team discovered that normal cells can enter an unstable critical transition state where normal cells and cancer cells coexist just before they change into cancer cells during tumorigenesis, the production or development of tumors, and analyzed this critical transition state using a systems biology method to develop a cancer reversal molecular switch identification technology that can reverse the cancerization process. They then applied this to colon cancer cells and confirmed through molecular cell experiments that cancer cells can recover the characteristics of normal cells.
This is an original technology that automatically infers a computer model of the genetic network that controls the critical transition of cancer development from single-cell RNA sequencing data, and systematically finds molecular switches for cancer reversion by simulation analysis. It is expected that this technology will be applied to the development of reversion therapies for other cancers in the future.
Professor Kwang-Hyun Cho said, "We have discovered a molecular switch that can revert the fate of cancer cells back to a normal state by capturing the moment of critical transition right before normal cells are changed into an irreversible cancerous state."
< Figure 1. Overall conceptual framework of the technology that automatically constructs a molecular regulatory network from single-cell RNA sequencing data of colon cancer cells to discover molecular switches for cancer reversion through computer simulation analysis. Professor Kwang-Hyun Cho's research team established a fundamental technology for automatic construction of a computer model of a core gene network by analyzing the entire process of tumorigenesis of colon cells turning into cancer cells, and developed an original technology for discovering the molecular switches that can induce cancer cell reversal through attractor landscape analysis. >
He continued, "In particular, this study has revealed in detail, at the genetic network level, what changes occur within cells behind the process of cancer development, which has been considered a mystery until now." He emphasized, "This is the first study to reveal that an important clue that can revert the fate of tumorigenesis is hidden at this very critical moment of change."
< Figure 2. Identification of tumor transition state using single-cell RNA sequencing data from colorectal cancer. Using single-cell RNA sequencing data from colorectal cancer patient-derived organoids for normal and cancerous tissues, a critical transition was identified in which normal and cancerous cells coexist and instability increases (a-d). The critical transition was confirmed to show intermediate levels of major phenotypic features related to cancer or normal tissues that are indicative of the states between the normal and cancerous cells (e). >
The results of this study, conducted by KAIST Dr. Dongkwan Shin (currently at the National Cancer Center), Dr. Jeong-Ryeol Gong, and doctoral student Seoyoon D. Jeong jointly with a research team at Seoul National University that provided the organoids (in vitro cultured tissues) from colon cancer patient, were published as an online paper in the international journal ‘Advanced Science’ published by Wiley on January 22nd.
(Paper title: Attractor landscape analysis reveals a reversion switch in the transition of colorectal tumorigenesis) (DOI: https://doi.org/10.1002/advs.202412503)
< Figure 3. Reconstruction of a dynamic network model for the transition state of colorectal cancer.
A new technology was established to build a gene network computer model that can simulate the dynamic changes between genes by integrating single-cell RNA sequencing data and existing experimental results on gene-to-gene interactions in the critical transition of cancer. (a). Using this technology, a gene network computer model for the critical transition of colorectal cancer was constructed, and the distribution of attractors representing normal and cancer cell phenotypes was investigated through attractor landscape analysis (b-e). >
This study was conducted with the support of the National Research Foundation of Korea under the Ministry of Science and ICT through the Mid-Career Researcher Program and Basic Research Laboratory Program and the Disease-Centered Translational Research Project of the Korea Health Industry Development Institute (KHIDI) of the Ministry of Health and Welfare.
< Figure 4. Quantification of attractor landscapes and discovery of transcription factors for cancer reversibility through perturbation simulation analysis. A methodology for implementing discontinuous attractor landscapes continuously from a computer model of gene networks and quantifying them as cancer scores was introduced (a), and attractor landscapes for the critical transition of colorectal cancer were secured (b-d). By tracking the change patterns of normal and cancer cell attractors through perturbation simulation analysis for each gene, the optimal combination of transcription factors for cancer reversion was discovered (e-h). This was confirmed in various parameter combinations as well (i). >
< Figure 5. Identification and experimental validation of the optimal target gene for cancer reversion. Among the common target genes of the discovered transcription factor combinations, we identified cancer reversing molecular switches that are predicted to suppress cancer cell proliferation and restore the characteristics of normal colon cells (a-d). When inhibitors for the molecular switches were treated to organoids derived from colon cancer patients, it was confirmed that cancer cell proliferation was suppressed and the expression of key genes related to cancer development was inhibited (e-h), and a group of genes related to normal colon epithelium was activated and transformed into a state similar to normal colon cells (i-j). >
< Figure 6. Schematic diagram of the research results. Professor Kwang-Hyun Cho's research team developed an original technology to systematically discover key molecular switches that can induce reversion of colon cancer cells through a systems biology approach using an attractor landscape analysis of a genetic network model for the critical transition at the moment of transformation from normal cells to cancer cells, and verified the reversing effect of actual colon cancer through cellular experiments. >
2025.02.05 View 16045 -
KAIST Uncovers the Principles of Gene Expression Regulation in Cancer and Cellular Functions
< (From left) Professor Seyun Kim, Professor Gwangrog Lee, Dr. Hyoungjoon Ahn, Dr. Jeongmin Yu, Professor Won-Ki Cho, and (below) PhD candidate Kwangmin Ryu of the Department of Biological Sciences>
A research team at KAIST has identified the core gene expression networks regulated by key proteins that fundamentally drive phenomena such as cancer development, metastasis, tissue differentiation from stem cells, and neural activation processes. This discovery lays the foundation for developing innovative therapeutic technologies.
On the 22nd of January, KAIST (represented by President Kwang Hyung Lee) announced that the joint research team led by Professors Seyun Kim, Gwangrog Lee, and Won-Ki Cho from the Department of Biological Sciences had uncovered essential mechanisms controlling gene expression in animal cells.
Inositol phosphate metabolites produced by inositol metabolism enzymes serve as vital secondary messengers in eukaryotic cell signaling systems and are broadly implicated in cancer, obesity, diabetes, and neurological disorders.
The research team demonstrated that the inositol polyphosphate multikinase (IPMK) enzyme, a key player in the inositol metabolism system, acts as a critical transcriptional activator within the core gene expression networks of animal cells. Notably, although IPMK was previously reported to play an important role in the transcription process governed by serum response factor (SRF), a representative transcription factor in animal cells, the precise mechanism of its action was unclear.
SRF is a transcription factor directly controlling the expression of at least 200–300 genes, regulating cell growth, proliferation, apoptosis, and motility, and is indispensable for organ development, such as in the heart.
The team discovered that IPMK binds directly to SRF, altering the three-dimensional structure of the SRF protein. This interaction facilitates the transcriptional activity of various genes through the SRF activated by IPMK, demonstrating that IPMK acts as a critical regulatory switch to enhance SRF's protein activity.
< Figure 1. The serum response factor (SRF) protein, a key transcription factor in animal cells, directly binds to inositol polyphosphate multikinase (IPMK) enzyme and undergoes structural change to acquire DNA binding ability, and precisely regulates growth and differentiation of animal cells through transcriptional activation. >
The team further verified that disruptions in the direct interaction between IPMK and SRF lead to the reduced functionality and activity of SRF, causing severe impairments in gene expression.
By highlighting the significance of the intrinsically disordered region (IDR) in SRF, the researchers underscored the biological importance of intrinsically disordered proteins (IDPs). Unlike most proteins that adopt distinct structures through folding, IDPs, including those with IDRs, do not exhibit specific structures but play crucial biological roles, attracting significant attention in the scientific community.
Professor Seyun Kim commented, "This study provides a vital mechanism proving that IPMK, a key enzyme in the inositol metabolism system, is a major transcriptional activator in the core gene expression network of animal cells. By understanding fundamental processes such as cancer development and metastasis, tissue differentiation from stem cells, and neural activation through SRF, we hope this discovery will lead to the broad application of innovative therapeutic technologies."
The findings were published on January 7th in the international journal Nucleic Acids Research (IF=16.7, top 1.8% in Biochemistry and Molecular Biology), under the title “Single-molecule analysis reveals that IPMK enhances the DNA-binding activity of the transcription factor SRF" (DOI: 10.1093/nar/gkae1281).
This research was supported by the National Research Foundation of Korea's Mid-career Research Program, Leading Research Center Program, and Global Research Laboratory Program, as well as by the Suh Kyungbae Science Foundation and the Samsung Future Technology Development Program.
2025.01.24 View 6393 -
KAIST Develops Insect-Eye-Inspired Camera Capturing 9,120 Frames Per Second
< (From left) Bio and Brain Engineering PhD Student Jae-Myeong Kwon, Professor Ki-Hun Jeong, PhD Student Hyun-Kyung Kim, PhD Student Young-Gil Cha, and Professor Min H. Kim of the School of Computing >
The compound eyes of insects can detect fast-moving objects in parallel and, in low-light conditions, enhance sensitivity by integrating signals over time to determine motion. Inspired by these biological mechanisms, KAIST researchers have successfully developed a low-cost, high-speed camera that overcomes the limitations of frame rate and sensitivity faced by conventional high-speed cameras.
KAIST (represented by President Kwang Hyung Lee) announced on the 16th of January that a research team led by Professors Ki-Hun Jeong (Department of Bio and Brain Engineering) and Min H. Kim (School of Computing) has developed a novel bio-inspired camera capable of ultra-high-speed imaging with high sensitivity by mimicking the visual structure of insect eyes.
High-quality imaging under high-speed and low-light conditions is a critical challenge in many applications. While conventional high-speed cameras excel in capturing fast motion, their sensitivity decreases as frame rates increase because the time available to collect light is reduced.
To address this issue, the research team adopted an approach similar to insect vision, utilizing multiple optical channels and temporal summation. Unlike traditional monocular camera systems, the bio-inspired camera employs a compound-eye-like structure that allows for the parallel acquisition of frames from different time intervals.
< Figure 1. (A) Vision in a fast-eyed insect. Reflected light from swiftly moving objects sequentially stimulates the photoreceptors along the individual optical channels called ommatidia, of which the visual signals are separately and parallelly processed via the lamina and medulla. Each neural response is temporally summed to enhance the visual signals. The parallel processing and temporal summation allow fast and low-light imaging in dim light. (B) High-speed and high-sensitivity microlens array camera (HS-MAC). A rolling shutter image sensor is utilized to simultaneously acquire multiple frames by channel division, and temporal summation is performed in parallel to realize high speed and sensitivity even in a low-light environment. In addition, the frame components of a single fragmented array image are stitched into a single blurred frame, which is subsequently deblurred by compressive image reconstruction. >
During this process, light is accumulated over overlapping time periods for each frame, increasing the signal-to-noise ratio. The researchers demonstrated that their bio-inspired camera could capture objects up to 40 times dimmer than those detectable by conventional high-speed cameras.
The team also introduced a "channel-splitting" technique to significantly enhance the camera's speed, achieving frame rates thousands of times faster than those supported by the image sensors used in packaging. Additionally, a "compressed image restoration" algorithm was employed to eliminate blur caused by frame integration and reconstruct sharp images.
The resulting bio-inspired camera is less than one millimeter thick and extremely compact, capable of capturing 9,120 frames per second while providing clear images in low-light conditions.
< Figure 2. A high-speed, high-sensitivity biomimetic camera packaged in an image sensor. It is made small enough to fit on a finger, with a thickness of less than 1 mm. >
The research team plans to extend this technology to develop advanced image processing algorithms for 3D imaging and super-resolution imaging, aiming for applications in biomedical imaging, mobile devices, and various other camera technologies.
Hyun-Kyung Kim, a doctoral student in the Department of Bio and Brain Engineering at KAIST and the study's first author, stated, “We have experimentally validated that the insect-eye-inspired camera delivers outstanding performance in high-speed and low-light imaging despite its small size. This camera opens up possibilities for diverse applications in portable camera systems, security surveillance, and medical imaging.”
< Figure 3. Rotating plate and flame captured using the high-speed, high-sensitivity biomimetic camera. The rotating plate at 1,950 rpm was accurately captured at 9,120 fps. In addition, the pinch-off of the flame with a faint intensity of 880 µlux was accurately captured at 1,020 fps. >
This research was published in the international journal Science Advances in January 2025 (Paper Title: “Biologically-inspired microlens array camera for high-speed and high-sensitivity imaging”).
DOI: https://doi.org/10.1126/sciadv.ads3389
This study was supported by the Korea Research Institute for Defense Technology Planning and Advancement (KRIT) of the Defense Acquisition Program Administration (DAPA), the Ministry of Science and ICT, and the Ministry of Trade, Industry and Energy (MOTIE).
2025.01.16 View 4373 -
KAIST Develops Foundational Technology to Revert Cancer Cells to Normal Cells
Despite the development of numerous cancer treatment technologies, the common goal of current cancer therapies is to eliminate cancer cells. This approach, however, faces fundamental limitations, including cancer cells developing resistance and returning, as well as severe side effects from the destruction of healthy cells.
< (From top left) Bio and Brain Engineering PhD candidates Juhee Kim, Jeong-Ryeol Gong, Chun-Kyung Lee, and Hoon-Min Kim posed for a group photo with Professor Kwang-Hyun Cho >
KAIST (represented by President Kwang Hyung Lee) announced on the 20th of December that a research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering has developed a groundbreaking technology that can treat colon cancer by converting cancer cells into a state resembling normal colon cells without killing them, thus avoiding side effects.
The research team focused on the observation that during the oncogenesis process, normal cells regress along their differentiation trajectory. Building on this insight, they developed a technology to create a digital twin of the gene network associated with the differentiation trajectory of normal cells.
< Figure 1. Technology for creating a digital twin of a gene network from single-cell transcriptome data of a normal cell differentiation trajectory. Professor Kwang-Hyun Cho's research team developed a digital twin creation technology that precisely observes the dynamics of gene regulatory relationships during the process of normal cells differentiating along a differentiation trajectory and analyzes the relationships among key genes to build a mathematical model that can be simulated (A-F). In addition, they developed a technology to discover key regulatory factors that control the differentiation trajectory of normal cells by simulating and analyzing this digital twin. >
< Figure 2. Digital twin simulation simulating the differentiation trajectory of normal colon cells. The dynamics of single-cell transcriptome data for the differentiation trajectory of normal colon cells were analyzed (A) and a digital twin of the gene network was developed representing the regulatory relationships of key genes in this differentiation trajectory (B). The simulation results of the digital twin confirm that it readily reproduces the dynamics of single-cell transcriptome data (C, D). >
Through simulation analysis, the team systematically identified master molecular switches that induce normal cell differentiation. When these switches were applied to colon cancer cells, the cancer cells reverted to a normal-like state, a result confirmed through molecular and cellular experiments as well as animal studies.
< Figure 3. Discovery of top-level key control factors that induce differentiation of normal colon cells. By applying control factor discovery technology to the digital twin model, three genes, HDAC2, FOXA2, and MYB, were discovered as key control factors that induce differentiation of normal colon cells (A, B). The results of simulation analysis of the regulatory effects of the discovered control factors through the digital twin confirmed that they could induce complete differentiation of colon cells (C). >
< Figure 4. Verification of the effect of the key control factors discovered using colon cancer cells and animal experiments on the reversibility of colon cancer. The key control factors of the normal colon cell differentiation trajectory discovered through digital twin simulation analysis were applied to actual colon cancer cells and colon cancer mouse animal models to experimentally verify the effect of cancer reversibility. The key control factors significantly reduced the proliferation of three colon cancer cell lines (A), and this was confirmed in the same way in animal models (B-D). >
This research demonstrates that cancer cell reversion can be systematically achieved by analyzing and utilizing the digital twin of the cancer cell gene network, rather than relying on serendipitous discoveries. The findings hold significant promise for developing reversible cancer therapies that can be applied to various types of cancer.
< Figure 5. The change in overall gene expression was confirmed through the regulation of the identified key regulatory factors, which converted the state of colon cancer cells to that of normal colon cells. The transcriptomes of colon cancer tissues and normal colon tissues from more than 400 colon cancer patients were compared with the transcriptomes of colon cancer cell lines and reversible colon cancer cell lines, respectively. The comparison results confirmed that the regulation of the identified key regulatory factors converted all three colon cancer cell lines to a state similar to the transcriptome expression of normal colon tissues. >
Professor Kwang-Hyun Cho remarked, "The fact that cancer cells can be converted back to normal cells is an astonishing phenomenon. This study proves that such reversion can be systematically induced."
He further emphasized, "This research introduces the novel concept of reversible cancer therapy by reverting cancer cells to normal cells. It also develops foundational technology for identifying targets for cancer reversion through the systematic analysis of normal cell differentiation trajectories."
This research included contributions from Jeong-Ryeol Gong, Chun-Kyung Lee, Hoon-Min Kim, Juhee Kim, and Jaeog Jeon, and was published in the online edition of the international journal Advanced Science by Wiley on December 11. (Title: “Control of Cellular Differentiation Trajectories for Cancer Reversion”) DOI: https://doi.org/10.1002/advs.202402132
< Figure 6. Schematic diagram of the research results. Professor Kwang-Hyun Cho's research team developed a source technology to systematically discover key control factors that can induce reversibility of colon cancer cells through a systems biology approach and a digital twin simulation analysis of the differentiation trajectory of normal colon cells, and verified the effects of reversion on actual colon cancer through molecular cell experiments and animal experiments. >
The study was supported by the Ministry of Science and ICT and the National Research Foundation of Korea through the Mid-Career Researcher Program and Basic Research Laboratory Program. The research findings have been transferred to BioRevert Inc., where they will be used for the development of practical cancer reversion therapies.
2024.12.23 View 78370 -
KAIST Unveils New Possibilities for Treating Intractable Brain Tumors
< Photo 1. (From left) Professor Heung Kyu Lee, KAIST Department of Biological Sciences, and Dr. Keun Bon Ku >
Immunotherapy, which enhances the immune system's T cell response to eliminate cancer cells, has emerged as a key approach in cancer treatment. However, in the case of glioblastoma, an aggressive and treatment-resistant brain tumor, numerous clinical trials have failed to confirm their efficacy. Korean researchers have recently analyzed the mechanisms that cause T cell exhaustion, which is characterized by a loss of function or a weakened response following prolonged exposure to antigens in such intractable cancers, identifying key control factors in T cell activation and clarifying the mechanisms that enhance therapeutic effectiveness.
KAIST (represented by President Kwang Hyung Lee) announced on the 6th of November that Professor Heung Kyu Lee’s team from the Department of Biological Sciences, in collaboration with the Korea Research Institute of Chemical Technology (represented by President Young Kuk Lee), has confirmed improved survival rates in a glioblastoma mouse model. By removing the inhibitory Fc gamma receptor (FcγRIIB), the research team was able to restore the responsiveness of cytotoxic T cells to immune checkpoint inhibitors, leading to enhanced anticancer activity.
The research team examined the effect of FcγRIIB, an inhibitory receptor recently found in cytotoxic T cells, on tumor-infiltrating T cells and the therapeutic effectiveness of the anti-PD-1 immune checkpoint inhibitor.
< Figure 1. Study results on improved survival rate due to increased antitumor activity of anti-PD-1 treatment in inhibitory Fc gamma receptor(Fcgr2b) ablation mice with murine glioblastoma. >
Their findings showed that deleting FcγRIIB induced the increase of tumor antigen-specific memory T cells, which helps to suppress exhaustion, enhances stem-like qualities, and reactivates T cell-mediated antitumor immunity, particularly in response to anti-PD-1 treatment. Furthermore, FcγRIIB deletion led to an increase in antigen-specific memory T cells that maintained continuous infiltration into the tumor tissue.
This study presents a new therapeutic target for tumors unresponsive to immune checkpoint inhibitors and demonstrates that combining FcγRIIB inhibition with anti-PD-1 treatment can produce synergistic effects, potentially improving therapeutic outcomes for tumors like glioblastoma, which typically show resistance to anti-PD-1 therapy.
< Figure 2. Overview of the study on the enhanced response to anti-PD-1 therapy for glioblastoma brain tumors upon deletion of the inhibitory Fc gamma receptor (FcγRIIB) in tumor microenvironment. When the inhibitory Fc gamma receptor (FcγRIIB) of cytotoxic T cells is deleted, an increase in tumor-specific memory T cells (Ttsms) was observed. In addition, this T cell subset is identified as originating from the tumor-draining lymph nodes(TdLNs) and leads to persistent infiltration into the tumor tissue. Anti-PD-1 therapy leads to an increased anti-tumor immune response via Ttsms, which is confirmed by increased tumor cell toxicity and increased cell division and decreased cell de-migration indices. Ultimately, the increased cytotoxic T cell immune response leads to an increase in the survival rate of glioblastoma. >
Professor Heung Kyu Lee explained, "This study offers a way to overcome clinical failures in treating brain tumors with immune checkpoint therapy and opens possibilities for broader applications to other intractable cancers. It also highlights the potential of utilizing cytotoxic T cells for tumor cell therapy."
The study, led by Dr. Keun Bon Ku of KAIST (currently a senior researcher at the Korea Research Institute of Chemical Technology's Center for Infectious Disease Diagnosis and Prevention), along with Chae Won Kim, Yumin Kim, Byeong Hoon Kang, Jeongwoo La, In Kang, Won Hyung Park, Stephen Ahn, and Sung Ki Lee, was published online on October 26 in the Journal for ImmunoTherapy of Cancer, an international journal in tumor immunology and therapy from the Society for Immunotherapy of Cancer. (Paper title: “Inhibitory Fcγ receptor deletion enhances CD8 T cell stemness increasing anti-PD-1 therapy responsiveness against glioblastoma,” http://dx.doi.org/10.1136/jitc-2024-009449).
This research received support from the National Research Foundation of Korea, the Bio & Medical Technology Development Program, and the Samsung Science & Technology Foundation.
2024.11.15 View 2836 -
KAIST Researchers Suggest an Extraordinary Alternative to Petroleum-based PET - Bacteria!
< (From left) Dr. Cindy Pricilia, Ph.D. Candidate Cheon Woo Moon, Distinguished Professor Sang Yup Lee >
Currently, the world is suffering from environmental problems caused by plastic waste. The KAIST research team has succeeded in producing a microbial-based plastic that is biodegradable and can replace existing PET bottles, making it a hot topic.
Our university announced on the 7th of November that the research team of Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering has succeeded in developing a microbial strain that efficiently produces pseudoaromatic polyester monomer to replace polyethylene terephthalate (PET) using systems metabolic engineering.
Pseudoaromatic dicarboxylic acids have better physical properties and higher biodegradability than aromatic polyester (PET) when synthesized as polymers, and are attracting attention as an eco-friendly monomer* that can be synthesized into polymers. The production of pseudoaromatic dicarboxylic acids through chemical methods has the problems of low yield and selectivity, complex reaction conditions, and the generation of hazardous waste.
*Monomer: A material for making polymers, which is used to synthesize polymers by polymerizing monomers together
< Figure. Overview of pseudoaromatic dicarboxylic acid production using metabolically engineered C. glutamicum. >
To solve this problem, Professor Sang Yup Lee's research team used metabolic engineering to develop a microbial strain that efficiently produces five types of pseudoaromatic dicarboxylic acids, including 2-pyrone-4,6-dicarboxylic acid and four types of pyridine dicarboxylic acids (2,3-, 2,4-, 2,5-, 2,6-pyridine dicarboxylic acids), in Corynebacterium, a bacterium mainly used for amino acid production.
The research team used metabolic engineering techniques to build a platform microbial strain that enhances the metabolic flow of protocatechuic acid, which is used as a precursor for several pseudoaromatic dicarboxylic acids, and prevents the loss of precursors.
Based on this, the genetic manipulation target was discovered through transcriptome analysis, producing 76.17 g/L of 2-pyrone-4,6-dicarboxylic acid, and by newly discovering and constructing three types of pyridine dicarboxylic acid production metabolic pathways, successfully producing 2.79 g/L of 2,3-pyridine dicarboxylic acid, 0.49 g/L of 2,4-pyridine dicarboxylic acid, and 1.42 g/L of 2,5-pyridine dicarboxylic acid.
In addition, the research team confirmed the production of 15.01 g/L through the construction and reinforcement of the 2,6-pyridine dicarboxylic acid biosynthesis pathway, successfully producing a total of five similar aromatic dicarboxylic acids with high efficiency.
In conclusion, the team succeeded in producing 2,4-, 2,5-, and 2,6-pyridine dicarboxylic acids at the world's highest concentration. In particular, 2,4-, 2,5-pyridine dicarboxylic acid achieved production on the scale of g/L, which was previously produced in extremely small amounts (mg/L).
Based on this study, it is expected that it will be applied to various polyester production industrial processes, and it is also expected that it will be actively utilized in research on the production of similar aromatic polyesters.
Professor Sang Yup Lee, the corresponding author, said, “The significance lies in the fact that we have developed an eco-friendly technology that efficiently produces similar aromatic polyester monomers based on microorganisms,” and “This study will help the microorganism-based bio-monomer industry replace the petrochemical-based chemical industry in the future.”
The results of this study were published in the international academic journal, the Proceedings of the National Academy of Sciences of United States of America (PNAS) on October 30th.
※ Paper title: Metabolic engineering of Corynebacterium glutamicum for the production of pyrone and pyridine dicarboxylic acids
※ Author information: Jae Sung Cho (co-first author), Zi Wei Luo (co-first author), Cheon Woo Moon (co-first author), Cindy Prabowo (co-author), Sang Yup Lee (corresponding author) - a total of 5 people
This study was conducted with the support of the Development of Next-generation Biorefinery Platform Technologies for Leading Bio-based Chemicals Industry Project and the Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project (Project leader: Professor Sang Yup Lee) from the National Research Foundation supported by the Ministry of Science and Technology and ICT of Korea.
2024.11.08 View 5641 -
Professor Jimin Park and Dr. Inho Kim join the ranks of the 2024 "35 Innovators Under 35" by the MIT Technology Review
< (From left) Professor Jimin Park of the Department of Chemical and Biomolecular Engineering and Dr. Inho Kim, a graduate of the Department of Materials Science and Engineering >
KAIST (represented by President Kwang-Hyung Lee) announced on the 13th of September that Professor Jimin Park from KAIST’s Department of Chemical and Biomolecular Engineering and Dr. Inho Kim, a graduate from the Department of Materials Science and Engineering (currently a postdoctoral researcher at Caltech), were selected by the MIT Technology Review as the 2024 "35 Innovators Under 35”.
The MIT Technology Review, first published in 1899 by the Massachusetts Institute of Technology, is the world’s oldest and most influential magazine on science and technology, offering in-depth analysis across various technology fields, expanding knowledge and providing insights into cutting-edge technology trends.
Since 1999, the magazine has annually named 35 innovators under the age of 35, recognizing young talents making groundbreaking contributions in modern technology fields. The recognition is globally considered a prestigious honor and a dream for young researchers in the science and technology community.
< Image 1. Introduction for Professor Jimin Park at the Meet 35 Innovators Under 35 Summit 2024 >
Professor Jimin Park is developing next-generation bio-interfaces that link artificial materials with living organisms, and is engaged in advanced research in areas such as digital healthcare and carbon-neutral compound manufacturing technologies. In 2014, Professor Park was also recognized as one of the ‘Asia Pacific Innovators Under 35’ by the MIT Technology Review, which highlights young scientists in the Asia-Pacific region.
Professor Park responded, “It’s a great honor to be named as one of the young innovators by the MIT Technology Review, a symbol of innovation with a long history. I will continue to pursue challenging, interdisciplinary research to develop next-generation interfaces that seamlessly connect artificial materials and living organisms, from atomic to system levels.”
< Image 2. Introduction for Dr. Inho Kim as the 2024 Innovator of Materials Science for 35 Innovators Under 35 >
Dr. Inho Kim, who earned his PhD from KAIST in 2020 under the supervision of Professor Sang Ouk Kim from the Department of Materials Science and Engineering, recently succeeded in developing a new artificial muscle using composite fibers. This new material is considered the most human-like muscle ever reported in scientific literature, while also being 17 times stronger than natural human muscle.
Dr. Kim is researching the application of artificial muscle fibers in next-generation wearable assistive devices that move more naturally, like humans or animals, noting that the fibers are lightweight, flexible, and exhibit conductivity during contraction, enabling real-time feedback. Recognized for this potential, Dr. Inho Kim was named one of the '35 Innovators Under 35' this year, making him the first researcher to win the honor with the research conducted at KAIST and a PhD earned from Korea.
Dr. Kim stated, “I aim to develop robots using these new materials that can replace today’s expensive and heavy exoskeleton suits by eliminating motors and rigid frames. This will significantly reduce costs and allow for better customization, making cutting-edge technology more accessible to those who need it most, like children with cerebral palsy.”
2024.09.13 View 4490