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The cause of disability in aged brain meningeal membranes identified
Due to the increase in average age, studies on changes in the brain following general aging process without serious brain diseases have also become an issue that requires in-depth studies. Regarding aging research, as aging progresses, ‘sugar’ accumulates in the body, and the accumulated sugar becomes a causative agent for various diseases such as aging-related inflammation and vascular disease. In the end, “surplus” sugar molecules attach to various proteins in the body and interfere with their functions. KAIST (President Kwang Hyung Lee), a joint research team of Professor Pilnam Kim and Professor Yong Jeong of the Department of Bio and Brain Engineering, revealed on the 15th that it was confirmed that the function of being the “front line of defense” for the cerebrocortex of the brain meninges, the layers of membranes that surrounds the brain, is hindered when 'sugar' begins to build up on them as aging progresses. Professor Kim's research team confirmed excessive accumulation of sugar molecules in the meninges of the elderly and also confirmed that sugar accumulation occurs mouse models in accordance with certain age levels. The meninges are thin membranes that surround the brain and exist at the boundary between the cerebrospinal fluid and the cortex and play an important role in protecting the brain. In this study, it was revealed that the dysfunction of these brain membranes caused by aging is induced by 'excess' sugar in the brain. In particular, as the meningeal membrane becomes thinner and stickier due to aging, a new paradigm has been provided for the discovery of the principle of the decrease in material exchange between the cerebrospinal fluid and the cerebral cortex. This research was conducted by the Ph.D. candidate Hyo Min Kim and Dr. Shinheun Kim as the co-first authors to be published online on February 28th in the international journal, Aging Cell. (Paper Title: Glycation-mediated tissue-level remodeling of brain meningeal membrane by aging) The meninges, which are in direct contact with the cerebrospinal fluid, are mainly composed of collagen, an extracellular matrix (ECM) protein, and are composed of fibroblasts, which are cells that produce this protein. The cells that come in contact with collagen proteins that are attached with sugar have a low collagen production function, while the meningeal membrane continuously thins and collapses as the expression of collagen degrading enzymes increases. Studies on the relationship between excess sugar molecules accumulation in the brain due to continued sugar intake and the degeneration of neurons and brain diseases have been continuously conducted. However, this study was the first to identify meningeal degeneration and dysfunction caused by glucose accumulation with the focus on the meninges itself, and the results are expected to present new ideas for research into approach towards discoveries of new treatments for brain disease. Researcher Hyomin Kim, the first author, introduced the research results as “an interesting study that identified changes in the barriers of the brain due to aging through a convergent approach, starting from the human brain and utilizing an animal model with a biomimetic meningeal model”. Professor Pilnam Kim's research team is conducting research and development to remove sugar that accumulated throughout the human body, including the meninges. Advanced glycation end products, which are waste products formed when proteins and sugars meet in the human body, are partially removed by macrophages. However, glycated products bound to extracellular matrix proteins such as collagen are difficult to remove naturally. Through the KAIST-Ceragem Research Center, this research team is developing a healthcare medical device to remove 'sugar residue' in the body. This study was carried out with the National Research Foundation of Korea's collective research support. Figure 1. Schematic diagram of proposed mechanism showing aging‐related ECM remodeling through meningeal fibroblasts on the brain leptomeninges. Meningeal fibroblasts in the young brain showed dynamic COL1A1 synthetic and COL1‐interactive function on the collagen membrane. They showed ITGB1‐mediated adhesion on the COL1‐composed leptomeningeal membrane and induction of COL1A1 synthesis for maintaining the collagen membrane. With aging, meningeal fibroblasts showed depletion of COL1A1 synthetic function and altered cell–matrix interaction. Figure 2. Representative rat meningeal images observed in the study. Compared to young rats, it was confirmed that type 1 collagen (COL1) decreased along with the accumulation of glycated end products (AGE) in the brain membrane of aged rats, and the activity of integrin beta 1 (ITGB1), a representative receptor corresponding to cell-collagen interaction. Instead, it was observed that the activity of discoidin domain receptor 2 (DDR2), one of the tyrosine kinases, increased. Figure 3. Substance flux through the brain membrane decreases with aging. It was confirmed that the degree of adsorption of fluorescent substances contained in cerebrospinal fluid (CSF) to the brain membrane increased and the degree of entry into the periphery of the cerebral blood vessels decreased in the aged rats. In this study, only the influx into the brain was confirmed during the entry and exit of substances, but the degree of outflow will also be confirmed through future studies.
KAIST develops 'MetaVRain' that realizes vivid 3D real-life images
KAIST (President Kwang Hyung Lee) is a high-speed, low-power artificial intelligence (AI: Artificial Intelligent) semiconductor* MetaVRain, which implements artificial intelligence-based 3D rendering that can render images close to real life on mobile devices. * AI semiconductor: Semiconductor equipped with artificial intelligence processing functions such as recognition, reasoning, learning, and judgment, and implemented with optimized technology based on super intelligence, ultra-low power, and ultra-reliability The artificial intelligence semiconductor developed by the research team makes the existing ray-tracing*-based 3D rendering driven by GPU into artificial intelligence-based 3D rendering on a newly manufactured AI semiconductor, making it a 3D video capture studio that requires enormous costs. is not needed, so the cost of 3D model production can be greatly reduced and the memory used can be reduced by more than 180 times. In particular, the existing 3D graphic editing and design, which used complex software such as Blender, is replaced with simple artificial intelligence learning, so the general public can easily apply and edit the desired style. * Ray-tracing: Technology that obtains images close to real life by tracing the trajectory of all light rays that change according to the light source, shape and texture of the object This research, in which doctoral student Donghyun Han participated as the first author, was presented at the International Solid-State Circuit Design Conference (ISSCC) held in San Francisco, USA from February 18th to 22nd by semiconductor researchers from all over the world. (Paper Number 2.7, Paper Title: MetaVRain: A 133mW Real-time Hyper-realistic 3D NeRF Processor with 1D-2D Hybrid Neural Engines for Metaverse on Mobile Devices (Authors: Donghyeon Han, Junha Ryu, Sangyeob Kim, Sangjin Kim, and Hoi-Jun Yoo)) Professor Yoo's team discovered inefficient operations that occur when implementing 3D rendering through artificial intelligence, and developed a new concept semiconductor that combines human visual recognition methods to reduce them. When a person remembers an object, he has the cognitive ability to immediately guess what the current object looks like based on the process of starting with a rough outline and gradually specifying its shape, and if it is an object he saw right before. In imitation of such a human cognitive process, the newly developed semiconductor adopts an operation method that grasps the rough shape of an object in advance through low-resolution voxels and minimizes the amount of computation required for current rendering based on the result of rendering in the past. MetaVRain, developed by Professor Yu's team, achieved the world's best performance by developing a state-of-the-art CMOS chip as well as a hardware architecture that mimics the human visual recognition process. MetaVRain is optimized for artificial intelligence-based 3D rendering technology and achieves a rendering speed of up to 100 FPS or more, which is 911 times faster than conventional GPUs. In addition, as a result of the study, the energy efficiency, which represents the energy consumed per video screen processing, is 26,400 times higher than that of GPU, opening the possibility of artificial intelligence-based real-time rendering in VR/AR headsets and mobile devices. To show an example of using MetaVRain, the research team developed a smart 3D rendering application system together, and showed an example of changing the style of a 3D model according to the user's preferred style. Since you only need to give artificial intelligence an image of the desired style and perform re-learning, you can easily change the style of the 3D model without the help of complicated software. In addition to the example of the application system implemented by Professor Yu's team, it is expected that various application examples will be possible, such as creating a realistic 3D avatar modeled after a user's face, creating 3D models of various structures, and changing the weather according to the film production environment. do. Starting with MetaVRain, the research team expects that the field of 3D graphics will also begin to be replaced by artificial intelligence, and revealed that the combination of artificial intelligence and 3D graphics is a great technological innovation for the realization of the metaverse. Professor Hoi-Jun Yoo of the Department of Electrical and Electronic Engineering at KAIST, who led the research, said, “Currently, 3D graphics are focused on depicting what an object looks like, not how people see it.” The significance of this study was revealed as a study that enabled efficient 3D graphics by borrowing the way people recognize and express objects by imitating them.” He also foresaw the future, saying, “The realization of the metaverse will be achieved through innovation in artificial intelligence technology and innovation in artificial intelligence semiconductors, as shown in this study.” Figure 1. Description of the MetaVRain demo screen Photo of Presentation at the International Solid-State Circuits Conference (ISSCC)
KAIST team develops smart immune system that can pin down on malignant tumors
A joint research team led by Professor Jung Kyoon Choi of the KAIST Department of Bio and Brain Engineering and Professor Jong-Eun Park of the KAIST Graduate School of Medical Science and Engineering (GSMSE) announced the development of the key technologies to treat cancers using smart immune cells designed based on AI and big data analysis. This technology is expected to be a next-generation immunotherapy that allows precision targeting of tumor cells by having the chimeric antigen receptors (CARs) operate through a logical circuit. Professor Hee Jung An of CHA Bundang Medical Center and Professor Hae-Ock Lee of the Catholic University of Korea also participated in this research to contribute joint effort. Professor Jung Kyoon Choi’s team built a gene expression database from millions of cells, and used this to successfully develop and verify a deep-learning algorithm that could detect the differences in gene expression patterns between tumor cells and normal cells through a logical circuit. CAR immune cells that were fitted with the logic circuits discovered through this methodology could distinguish between tumorous and normal cells as a computer would, and therefore showed potentials to strike only on tumor cells accurately without causing unwanted side effects. This research, conducted by co-first authors Dr. Joonha Kwon of the KAIST Department of Bio and Brain Engineering and Ph.D. candidate Junho Kang of KAIST GSMSE, was published by Nature Biotechnology on February 16, under the title Single-cell mapping of combinatorial target antigens for CAR switches using logic gates. An area in cancer research where the most attempts and advances have been made in recent years is immunotherapy. This field of treatment, which utilizes the patient’s own immune system in order to overcome cancer, has several methods including immune checkpoint inhibitors, cancer vaccines and cellular treatments. Immune cells like CAR-T or CAR-NK equipped with chimera antigen receptors, in particular, can recognize cancer antigens and directly destroy cancer cells. Starting with its success in blood cancer treatment, scientists have been trying to expand the application of CAR cell therapy to treat solid cancer. But there have been difficulties to develop CAR cells with effective killing abilities against solid cancer cells with minimized side effects. Accordingly, in recent years, the development of smarter CAR engineering technologies, i.e., computational logic gates such as AND, OR, and NOT, to effectively target cancer cells has been underway. At this point in time, the research team built a large-scale database for cancer and normal cells to discover the exact genes that are expressed only from cancer cells at a single-cell level. The team followed this up by developing an AI algorithm that could search for a combination of genes that best distinguishes cancer cells from normal cells. This algorithm, in particular, has been used to find a logic circuit that can specifically target cancer cells through cell-level simulations of all gene combinations. CAR-T cells equipped with logic circuits discovered through this methodology are expected to distinguish cancerous cells from normal cells like computers, thereby minimizing side effects and maximizing the effects of chemotherapy. Dr. Joonha Kwon, who is the first author of this paper, said, “this research suggests a new method that hasn’t been tried before. What’s particularly noteworthy is the process in which we found the optimal CAR cell circuit through simulations of millions of individual tumors and normal cells.” He added, “This is an innovative technology that can apply AI and computer logic circuits to immune cell engineering. It would contribute greatly to expanding CAR therapy, which is being successfully used for blood cancer, to solid cancers as well.” This research was funded by the Original Technology Development Project and Research Program for Next Generation Applied Omic of the Korea Research Foundation. Figure 1. A schematic diagram of manufacturing and administration process of CAR therapy and of cancer cell-specific dual targeting using CAR. Figure 2. Deep learning (convolutional neural networks, CNNs) algorithm for selection of dual targets based on gene combination (left) and algorithm for calculating expressing cell fractions by gene combination according to logical circuit (right).
KAIST researchers discovers the neural circuit that reacts to alarm clock
KAIST (President Kwang Hyung Lee) announced on the 20th that a research team led by Professor Daesoo Kim of the Department of Brain and Cognitive Sciences and Dr. Jeongjin Kim 's team from the Korea Institute of Science and Technology (KIST) have identified the principle of awakening animals by responding to sounds even while sleeping. Sleep is a very important physiological process that organizes brain activity and maintains health. During sleep, the function of sensory nerves is blocked, so the ability to detect danger in the proximity is reduced. However, many animals detect approaching predators and respond even while sleeping. Scientists thought that animals ready for danger by alternating between deep sleep and light sleep. A research team led by Professor Daesoo Kim at KAIST discovered that animals have neural circuits that respond to sounds even during deep sleep. While awake, the medial geniculate thalamus responds to sounds, but during deep sleep, or Non-REM sleep, the Mediodorsal thalamus responds to sounds to wake up the brain. As a result of the study, when the rats fell into deep sleep, the nerves of the medial geniculate thalamus were also sleeping, but the nerves of mediodorsal thalamus were awake and responded immediately to sounds. In addition, it was observed that when mediodorsal thalamus was inhibited, the rats could not wake up even when a sound was heard, and when the mediodorsal thalamus was stimulated, the rats woke up within a few seconds without sound. This is the first study to show that sleep and wakefulness can transmit auditory signals through different neural circuits, and was reported in the international journal, Current Biology on February 7, and was highlighted by Nature. (https://www.nature.com/articles/d41586-023-00354-0) Professor Daesoo Kim explained, “The findings of this study can used in developing digital healthcare technologies to be used to improve understanding of disorders of senses and wakefulness seen in various brain diseases and to control the senses in the future.” This research was carried out with the support from the National Research Foundation of Korea's Mid-Career Research Foundation Program. Figure 1. Traditionally, sound signals were thought to be propagated from the auditory nerve to the auditory thalamus. However, while in slow-wave sleep, the auditory nerve sends sound signals to the mediodorsal thalamic neurons via the brainstem nerve to induce arousal in the brain. Figure 2. GRIK4 dorsomedial nerve in response to sound stimulation. The awakening effect is induced as the activity of the GRIK4 dorsal medial nerve increases based on the time when sound stimulation is given.
KAIST Holds 2023 Commencement Ceremony
< Photo 1. On the 17th, KAIST held the 2023 Commencement Ceremony for a total of 2,870 students, including 691 doctors. > KAIST held its 2023 commencement ceremony at the Sports Complex of its main campus in Daejeon at 2 p.m. on February 27. It was the first commencement ceremony to invite all its graduates since the start of COVID-19 quarantine measures. KAIST awarded a total of 2,870 degrees including 691 PhD degrees, 1,464 master’s degrees, and 715 bachelor’s degrees, which adds to the total of 74,999 degrees KAIST has conferred since its foundation in 1971, which includes 15,772 PhD, 38,360 master’s and 20,867 bachelor’s degrees. This year’s Cum Laude, Gabin Ryu, from the Department of Mechanical Engineering received the Minister of Science and ICT Award. Seung-ju Lee from the School of Computing received the Chairman of the KAIST Board of Trustees Award, while Jantakan Nedsaengtip, an international student from Thailand received the KAIST Presidential Award, and Jaeyong Hwang from the Department of Physics and Junmo Lee from the Department of Industrial and Systems Engineering each received the President of the Alumni Association Award and the Chairman of the KAIST Development Foundation Award, respectively. Minister Jong-ho Lee of the Ministry of Science and ICT awarded the recipients of the academic awards and delivered a congratulatory speech. Yujin Cha from the Department of Bio and Brain Engineering, who received a PhD degree after 19 years since his entrance to KAIST as an undergraduate student in 2004 gave a speech on behalf of the graduates to move and inspire the graduates and the guests. After Cha received a bachelor’s degree from the Department of Nuclear and Quantum Engineering, he entered a medical graduate school and became a radiation oncology specialist. But after experiencing the death of a young patient who suffered from osteosarcoma, he returned to his alma mater to become a scientist. As he believes that science and technology is the ultimate solution to the limitations of modern medicine, he started as a PhD student at the Department of Bio and Brain Engineering in 2018, hoping to find such solutions. During his course, he identified the characteristics of the decision-making process of doctors during diagnosis, and developed a brain-inspired AI algorithm. It is an original and challenging study that attempted to develop a fundamental machine learning theory from the data he collected from 200 doctors of different specialties. Cha said, “Humans and AI can cooperate by humans utilizing the unique learning abilities of AI to develop our expertise, while AIs can mimic us humans’ learning abilities to improve.” He added, “My ultimate goal is to develop technology to a level at which humans and machines influence each other and ‘coevolve’, and applying it not only to medicine, but in all areas.” Cha, who is currently an assistant professor at the KAIST Biomedical Research Center, has also written Artificial Intelligence for Doctors in 2017 to help medical personnel use AI in clinical fields, and the book was selected as one of the 2018 Sejong Books in the academic category. During his speech at this year’s commencement ceremony, he shared that “there are so many things in the world that are difficult to solve and many things to solve them with, but I believe the things that can really broaden the horizons of the world and find fundamental solutions to the problems at hand are science and technology.” Meanwhile, singer-songwriter Sae Byul Park who studied at the KAIST Graduate School of Culture Technology will also receive her PhD degree. Natural language processing (NLP) is a field in AI that teaches a computer to understand and analyze human language that is actively being studied. An example of NLP is ChatGTP, which recently received a lot of attention. For her research, Park analyzed music rather than language using NLP technology. To analyze music, which is in the form of sound, using the methods for NLP, it is necessary to rebuild notes and beats into a form of words or sentences as in a language. For this, Park designed an algorithm called Mel2Word and applied it to her research. She also suggested that by converting melodies into texts for analysis, one would be able to quantitatively express music as sentences or words with meaning and context rather than as simple sounds representing a certain note. Park said, “music has always been considered as a product of subjective emotion, but this research provides a framework that can calculate and analyze music.” Park’s study can later be developed into a tool to measure the similarities between musical work, as well as a piece’s originality, artistry and popularity, and it can be used as a clue to explore the fundamental principles of how humans respond to music from a cognitive science perspective. Park began her Ph.D. program in 2014, while carrying on with her musical activities as well as public and university lectures alongside, and dealing with personally major events including marriage and childbirth during the course of years. She already met the requirements to receive her degree in 2019, but delayed her graduation in order to improve the level of completion of her research, and finally graduated with her current achievements after nine years. Professor Juhan Nam, who supervised Park’s research, said, “Park, who has a bachelor’s degree in psychology, later learned to code for graduate school, and has complete high-quality research in the field of artificial intelligence.” He added, “Though it took a long time, her attitude of not giving up until the end as a researcher is also excellent.” Sae Byul Park is currently lecturing courses entitled Culture Technology and Music Information Retrieval at the Underwood International College of Yonsei University. Park said, “the 10 or so years I’ve spent at KAIST as a graduate student was a time I could learn and prosper not only academically but from all angles of life.” She added, “having received a doctorate degree is not the end, but a ‘commencement’. Therefore, I will start to root deeper from the seeds I sowed and work harder as a both a scholar and an artist.” < Photo 2. From left) Yujin Cha (Valedictorian, Medical-Scientist Program Ph.D. graduate), Saebyeol Park (a singer-songwriter, Ph.D. graduate from the Graduate School of Culture and Technology), Junseok Moon and Inah Seo (the two highlighted CEO graduates from the Department of Management Engineering's master’s program) > Young entrepreneurs who dream of solving social problems will also be wearing their graduation caps. Two such graduates are Jun-seok Moon and Inah Seo, receiving their master’s degrees in social entrepreneurship MBA from the KAIST College of Business. Before entrance, Moon ran a café helping African refugees stand on their own feet. Then, he entered KAIST to later expand his business and learn social entrepreneurship in order to sustainably help refugees in the blind spots of human rights and welfare. During his master’s course, Moon realized that he could achieve active carbon reduction by changing the coffee alone, and switched his business field and founded Equal Table. The amount of carbon an individual can reduce by refraining from using a single paper cup is 10g, while changing the coffee itself can reduce it by 300g. 1kg of coffee emits 15kg of carbon over the course of its production, distribution, processing, and consumption, but Moon produces nearly carbon-neutral coffee beans by having innovated the entire process. In particular, the company-to-company ESG business solution is Moon’s new start-up area. It provides companies with carbon-reduced coffee made by roasting raw beans from carbon-neutral certified farms with 100% renewable energy, and shows how much carbon has been reduced in its making. Equal Table will launch the service this month in collaboration with SK Telecom, its first partner. Inah Seo, who also graduated with Moon, founded Conscious Wear to start a fashion business reducing environmental pollution. In order to realize her mission, she felt the need to gain the appropriate expertise in management, and enrolled for the social entrepreneurship MBA. Out of the various fashion industries, Seo focused on the leather market, which is worth 80 trillion won. Due to thickness or contamination issues, only about 60% of animal skin fabric is used, and the rest is discarded. Heavy metals are used during such processes, which also directly affects the environment. During the social entrepreneurship MBA course, Seo collaborated with SK Chemicals, which had links through the program, and launched eco-friendly leather bags. The bags used discarded leather that was recycled by grinding and reprocessing into a biomaterial called PO3G. It was the first case in which PO3G that is over 90% biodegradable was applied to regenerated leather. In other words, it can reduce environmental pollution in the processing and disposal stages, while also reducing carbon emissions and water usage by one-tenth compared to existing cowhide products. The social entrepreneurship MBA course, from which Moon and Seo graduated, will run in integration with the Graduate School of Green Growth as an Impact MBA program starting this year. KAIST plans to steadily foster entrepreneurs who will lead meaningful changes in the environment and society as well as economic values through innovative technologies and ideas. < Photo 3. NYU President Emeritus John Sexton (left), who received this year's honorary doctorate of science, poses with President Kwang Hyung Lee > Meanwhile, during this day’s commencement ceremony, KAIST also presented President Emeritus John Sexton of New York University with an honorary doctorate in science. He was recognized for laying the foundation for the cooperation between KAIST and New York University, such as promoting joint campuses. < Photo 4. At the commencement ceremony of KAIST held on the 17th, President Kwang Hyung Lee is encouraging the graduates with his commencement address. > President Kwang Hyung Lee emphasized in his commencement speech that, “if you can draw up the future and work hard toward your goal, the future can become a work of art that you create with your own hands,” and added, “Never stop on the journey toward your dreams, and do not give up even when you are met with failure. Failure happens to everyone, all the time. The important thing is to know 'why you failed', and to use those elements of failure as the driving force for the next try.”
KAIST presents a fundamental technology to remove metastatic traits from lung cancer cells
KAIST (President Kwang Hyung Lee) announced on January 30th that a research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering succeeded in using systems biology research to change the properties of carcinogenic cells in the lungs and eliminate both drug resistance and their ability to proliferate out to other areas of the body. As the incidences of cancer increase within aging populations, cancer has become the most lethal disease threatening healthy life. Fatality rates are especially high when early detection does not happen in time and metastasis has occurred in various organs. In order to resolve this problem, a series of attempts were made to remove or lower the ability of cancer cells to spread, but they resulted in cancer cells in the intermediate state becoming more unstable and even more malignant, which created serious treatment challenges. Professor Kwang-Hyun Cho's research team simulated various cancer cell states in the Epithelial-to-Mesenchymal Transition (EMT) of lung cancer cells, between epithelial cells without metastatic ability and mesenchymal cells with metastatic ability. A mathematical model of molecular network was established, and key regulators that could reverse the state of invasive and drug resistant mesenchymal cells back to the epithelial state were discovered through computer simulation analysis and molecular cell experiments. In particular, this process succeeded in properly reverting the mesenchymal lung cancer cells to a state where they were sensitive to chemotherapy treatment while avoiding the unstable EMT hybrid cell state in the middle process, which had remained a difficult problem. The results of this research, in which KAIST Ph.D. student Namhee Kim, Dr. Chae Young Hwang, Researcher Taeyoung Kim, and Ph.D. student Hyunjin Kim participated, were published as an online paper in the international journal “Cancer Research” published by the American Association for Cancer Research (AACR) on January 30th. (Paper title: A cell fate reprogramming strategy reverses epithelial-to-mesenchymal transition of lung cancer cells while avoiding hybrid states) Cells in an EMT hybrid state, which are caused by incomplete transitions during the EMT process in cancer cells, have the characteristics of both epithelial cells and mesenchymal cells, and are known to have high drug resistance and metastatic potential by acquiring high stem cell capacity. In particular, EMT is further enhanced through factors such as transforming growth factor-beta (TGF-β) secreted from the tumor microenvironment (TME) and, as a result, various cell states with high plasticity appear. Due to the complexity of EMT, it has been very difficult to completely reverse the transitional process of the mesenchymal cancer cells to an epithelial cell state in which metastatic ability and drug resistance are eliminated while avoiding the EMT hybrid cell state with high metastatic ability and drug resistance. Professor Kwang-Hyun Cho's research team established a mathematical model of the gene regulation network that governs the complex process of EMT, and then applied large-scale computer simulation analysis and complex system network control technology to identify and verify 'p53', 'SMAD4', and 'ERK1' and 'ERK 2' (collectively ERKs) through molecular cell experiments as the three key molecular targets that can transform lung cancer cells in the mesenchymal cell state, reversed back to an epithelial cell state that no longer demonstrates the ability to metastasize, while avoiding the EMT hybrid cell state. In particular, by analyzing the molecular regulatory mechanism of the complex EMT process at the system level, the key pathways were identified that were linked to the positive feedback that plays an important role in completely returning cancer cells to an epithelial cell state in which metastatic ability and drug resistance are removed. This discovery is significant in that it proved that mesenchymal cells can be reverted to the state of epithelial cells under conditions where TGF-β stimulation are present, like they are in the actual environment where cancer tissue forms in the human body. Abnormal EMT in cancer cells leads to various malignant traits such as the migration and invasion of cancer cells, changes in responsiveness to chemotherapy treatment, enhanced stem cell function, and the dissemination of cancer. In particular, the acquisition of the metastatic ability of cancer cells is a key determinant factor for the prognosis of cancer patients. The EMT reversal technology in lung cancer cells developed in this research is a new anti-cancer treatment strategy that reprograms cancer cells to eliminate their high plasticity and metastatic potential and increase their responsiveness to chemotherapy. Professor Kwang-Hyun Cho said, "By succeeding in reversing the state of lung cancer cells that acquired high metastatic traits and resistance to drugs and reverting them to a treatable epithelial cell state with renewed sensitivity to chemotherapy, the research findings propose a new strategy for treatments that can improve the prognosis of cancer patients.” Professor Kwang-Hyun Cho's research team was the first to present the principle of reversal treatment to revert cancer cells to normal cells, following through with the announcement of the results of their study that reverted colon cancer cells to normal colon cells in January of 2020, and also presenting successful re-programming research where the most malignant basal type breast cancer cells turned into less-malignant luminal type breast cancer cells that were treatable with hormonal therapies in January of 2022. This latest research result is the third in the development of reversal technology where lung cancer cells that had acquired metastatic traits returned to a state in which their metastatic ability was removed and drug sensitivity was enhanced. This research was carried out with support from the Ministry of Science and ICT and the National Research Foundation of Korea's Basic Research in Science & Engineering Program for Mid-Career Researchers. < Figure 1. Construction of the mathematical model of the regulatory network to represent the EMT phenotype based on the interaction between various molecules related to EMT. (A) Professor Kwang-Hyun Cho's research team investigated numerous literatures and databases related to complex EMT, and based on comparative analysis of cell line data showing epithelial and mesenchymal cell conditions, they extracted key signaling pathways related to EMT and built a mathematical model of regulatory network (B) By comparing the results of computer simulation analysis and the molecular cell experiments, it was verified how well the constructed mathematical model simulated the actual cellular phenomena. > < Figure 2. Understanding of various EMT phenotypes through large-scale computer simulation analysis and complex system network control technology. (A) Through computer simulation analysis and experiments, Professor Kwang-Hyun Cho's research team found that complete control of EMT is impossible with single-molecule control alone. In particular, through comparison of the relative stability of attractors, it was revealed that the cell state exhibiting EMT hybrid characteristics has unstable properties. (B), (C) Based on these results, Prof. Cho’s team identified two feedbacks (positive feedback consisting of Snail-miR-34 and ZEB1-miR-200) that play an important role in avoiding the EMT hybrid state that appeared in the TGF-β-ON state. It was found through computer simulation analysis that the two feedbacks restore relatively high stability when the excavated p53 and SMAD4 are regulated. In addition, molecular cell experiments demonstrated that the expression levels of E-cad and ZEB1, which are representative phenotypic markers of EMT, changed similarly to the expression profile in the epithelial cell state, despite the TGF-β-ON state. > < Figure 3. Complex molecular network analysis and discovery of reprogramming molecular targets for intact elimination of EMT hybrid features. (A) Controlling the expression of p53 and SMAD4 in lung cancer cell lines was expected to overcome drug resistance, but contrary to expectations, chemotherapy responsiveness was not restored. (B) Professor Kwang-Hyun Cho's research team additionally analyzed computer simulations, genome data, and experimental results and found that high expression levels of TWIST1 and EPCAM were related to drug resistance. (C) Prof. Cho’s team identified three key molecular targets: p53, SMAD4 and ERK1 & ERK2. (D), (E) Furthermore, they identified a key pathway that plays an important role in completely reversing into epithelial cells while avoiding EMT hybrid characteristics, and confirmed through network analysis and attractor analysis that high stability of the key pathway was restored when the proposed molecular target was controlled. > < Figure 4. Verification through experiments with lung cancer cell lines. When p53 was activated and SMAD4 and ERK1/2 were inhibited in lung cancer cell lines, (A), (B) E-cad protein expression increased and ZEB1 protein expression decreased, and (C) mesenchymal cell status including TWIST1 and EPCAM and gene expression of markers related to stem cell potential characteristics were completely inhibited. In addition, (D) it was confirmed that resistance to chemotherapy treatment was also overcome as the cell state was reversed by the regulated target. > < Figure 5. A schematic representation of the research results. Prof. Cho’s research team identified key molecular regulatory pathways to avoid high plasticity formed by abnormal EMT of cancer cells and reverse it to an epithelial cell state through systems biology research. From this analysis, a reprogramming molecular target that can reverse the state of mesenchymal cells with acquired invasiveness and drug resistance to the state of epithelial cells with restored drug responsiveness was discovered. For lung cancer cells, when a drug that enhances the expression of p53, one of the molecular targets discovered, and inhibits the expression of SMAD4 and ERK1 & ERK2 is administered, the molecular network of genes in the state of mesenchymal cells is modified, eventually eliminating metastatic ability and it is reprogrammed to turn into epithelial cells without the resistance to chemotherapy treatments. >
Afternoon chemotherapy proved to deliver more desirable results for female lymphoma patients
Chemotherapy is a commonly used regimen for cancer treatment, but it is also a double-edged sword. While the drugs are highly effective at killing cancer cells, they are also notorious for killing healthy cells in the body. As such, minimizing the drug’s damage to the patient’s body is necessary for improving the prognosis of chemotherapy. Recently, “chrono-chemotherapy” have been gaining interest in the research community. As the name suggests, the aim is timing the delivery of the drugs when the body is least vulnerable to their harmful effects and while the cancer cells are at their most vulnerable. < Figure 1. Chrono-chemotherapy considering circadian rhythm > Chrono-chemotherapy exploits the fact that human physiological processes, including cell proliferation and differentiation, are regulated by an endogenous timer called the circadian clock. However, this has not been widely exploited in real-world clinical settings because, as of now, there is no systematic method for finding the optimal chemotherapy delivery time. This problem was tackled by an interdisciplinary team of researchers from South Korea. They were led by principal investigators Jae Kyoung Kim (a mathematician from the Biomedical Mathematics Group, Institute for Basic Science) and Youngil Koh (an oncologist at Seoul National University Hospital). The researchers studied a group of patients suffering from diffuse large B-cell lymphoma (DLBCL). Terminology * Diffuse large B-cell lymphoma (DLBCL): Lymphoma is a type of blood cancer caused by the malignant transformation of lymphoid tissue cells. Lymphoma is divided into Hodgkin's lymphoma and non-Hodgkin's lymphoma (malignant lymphoma), and diffuse large B-cell lymphoma accounts for about 30 to 40% of non-Hodgkin's lymphoma. The research team noticed that DLBCL patients at Seoul National University Hospital received chemotherapy on two different schedules, with some patients receiving morning treatment (8:30 a.m.) and others taking the drugs in the afternoon (2:30 p.m.). All patients received the same cancer treatment (R-CHOP), which is a combination of targeted therapy and chemotherapy, four to six times in the morning or afternoon at intervals of about three weeks. They analyzed 210 patients to investigate whether there was any difference between morning and afternoon treatments. It was found that female patients who received the afternoon treatment had a 12.5 times reduced mortality rate (25% to 2%), while the cancer recurrence after 60 months decreased by 2.8 times (37% to 13%). In addition, chemotherapy side effects such as neutropenia were more common in female patients who received the morning treatment. Surprisingly, there was no differences found in treatment efficiency depending on the treatment schedule in the cases of male patients. To understand the cause of the gender differences, the research team analyzed upto 14,000 blood samples from the Seoul National University Hospital Health Examination Center. It was found that in females, white blood cell counts tended to decrease in the morning and increase in the afternoon. This indicates that the bone marrow proliferation rate was higher in the morning than in the afternoon because there is a upto 12 hour delay between bone marrow proliferation and blood cell production. This means that if a female patient receives chemotherapy in the morning when bone marrow is actively producing blood cells, the possibility of adverse side effects becomes greater. These results are consistent with the findings from recent randomized clinical trials that showed female colorectal cancer patients treated with irinotecan in the morning suffered from higher drug toxicities. One confounding variable was the drug dose. Since the morning female patients suffered from greater adverse side effects, oftentimes the dose had to be reduced for these patients. On average, the drug dose was reduced by upto 10% compared to the dose intensity given to female patients receiving the afternoon treatment. Unlike the female patients, it was found that male patients did not show a significant difference in white blood cell count and bone marrow cell proliferation activity throughout the day, which explains why the timing of the treatment had no impact. Professor Youngil Koh said, “We plan to verify the conclusions of this study again with a large-scale follow-up study that completely controls for the confounding variables, and to confirm whether chrono-chemotherapy has similar effects on other cancers.” CI Jae Kyoung Kim said, “Because the time of the internal circadian clock can vary greatly depending on the individual's sleep-wake patterns, we are currently developing a technology to estimate a patient’s circadian clock from their sleep pattern. We hope that this can be used to develop an individualized anti-cancer chronotherapy schedule.” < Figure 2. Chemotherapy in the afternoon can improve treatment outcomes. > The daily fluctuation of proliferative activity of bone marrow is larger in females than in males, and it becomes higher in the morning (left). Thus, chemotherapy in the morning strongly inhibits proliferative activity in female lymphoma patients, resulting in a higher incidence of adverse events such as neutropenia and infections. This forced the clinicians to reduce the dose intensity (center). Consequently, female patients undergoing the morning treatment showed a lower survival probability than those undergoing the afternoon treatment (right). Specifically, only ~13% of female patients treated in the afternoon had a worse outcome and ~2% of them died while ~37% of female patients treated in the morning had a worse outcome and ~25% of them died. Male patients did not show any difference in treatment outcomes depending on the chemotherapy delivery time.
Overview of the 30-year history of metabolic engineering
< Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering at KAIST > A research team comprised of Gi Bae Kim, Dr. So Young Choi, Dr. In Jin Cho, Da-Hee Ahn, and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering at KAIST reported the 30-year history of metabolic engineering, highlighting examples of recent progress in the field and contributions to sustainability and health. Their paper “Metabolic engineering for sustainability and health” was published online in the 40th anniversary special issue of Trends in Biotechnology on January 10, 2023. Metabolic engineering, a discipline of engineering that modifies cell phenotypes through molecular and genetic-level manipulations to improve cellular activities, has been studied since the early 1990s, and has progressed significantly over the past 30 years. In particular, metabolic engineering has enabled the engineering of microorganisms for the development of microbial cell factories capable of efficiently producing chemicals and materials as well as degrading recalcitrant contaminants. This review article revisited how metabolic engineering has advanced over the past 30 years, from the advent of genetic engineering techniques such as recombinant DNA technologies to recent breakthroughs in systems metabolic engineering and data science aided by artificial intelligence. The research team highlighted momentous events and achievements in metabolic engineering, providing both trends and future directions in the field. Metabolic engineering’s contributions to bio-based sustainable chemicals and clean energy, health, and bioremediation were also reviewed. Finally, the research team shared their perspectives on the future challenges impacting metabolic engineering than must be overcome in order to achieve advancements in sustainability and health. Distinguished Professor Sang Yup Lee said, “Replacing fossil resource-based chemical processes with bio-based sustainable processes for the production of chemicals, fuels, and materials using metabolic engineering has become our essential task for the future. By looking back on the 30+ years of metabolic engineering, we aimed to highlight the contributions of metabolic engineering to achieve sustainability and good health.” He added, “Metabolic engineering will play an increasingly important role as a key solution to the climate crisis, environmental pollution, food and energy shortages, and health problems in aging societies.” < Figure: Metabolic Engineering Timeline >
UAE Space Program Leaders named to be the 1st of the honorees of KAIST Alumni Association's special recognition for graduates of foreign nationality
The KAIST Alumni Association (Chairman, Chil-Hee Chung) announced on the 12th that the winners of the 2023 KAIST Distinguished Alumni Award and International Alumni Award has been selected. The KAIST Distinguished Alumni Award, which produced the first recipient in 1992, is an award given to alumni who have contributed to the development of the nation and society, or who have glorified the honor of their alma mater with outstanding academic achievements and social and/or communal contributions. On a special note, this year, there has been an addition to the honors, “the KAIST Distinguished International Alumni Award” to honor and encourage overseas alumni who are making their marks in the international community that will boost positive recognition of KAIST in the global setting and will later become a bridge that will expedite Korea's international efforts in the future. As of 2022, the number of international students who succeeded in earning KAIST degrees has exceeded 1,700, and they are actively doing their part back in their home countries as leaders in various fields in which they belong, spanning from science and technology, to politics, industry and other corners of the society. (From left) Omran Sharaf, the Assistant Minister of UAE Foreign Affairs and International Cooperation for Advanced Science and Technology, Amer Al Sayegh the Director General of Space Project at MBRSC, and Mohammed Al Harmi the Director General of Administration at MBRSC (Photos provided by the courtesy of MBRSC) To celebrate and honor their outstanding achievements, the KAIST Alumni Association selected a team of three alumni of the United Arab Emirates (UAE) to receive the Distinguished International Alumni Award for the first time. The named honorees are Omran Sharaf, a master’s graduate from the Graduate School of Science and Technology Policy, and Amer Al Sayegh and Mohammed Al Harmi, master’s graduates of the Department of Aerospace Engineering - all three of the class of 2013 in leading positions in the UAE space program to lead the advancement of the science and technology of the country. Currently, the three alums are in directorship of the Mohammed Bin Rashid Space Centre (MBRSC) with Mr. Omran Sharaf, who has recently been appointed as the Assistant Minister in charge of Advanced Science and Technology at the UAE Ministry of Foreign Affairs and International Cooperation, being the Project Director of the Emirates Mars Mission of MBRSC and Mr. Amer Al Sayegh in the Director General position in charge of Space Project and Mr. Mohammed Al Harmi, the Director General of Administration, at MBRSC. They received technology transfer from “SatRec I”, Korea's first satellite system exporter and KAIST alumni company, for about 10 years from 2006, while carrying out their master’s studies at the same time. Afterwards, they returned to UAE to lead the Emirates Mars Mission, which is already showing tangible progress including the successful launch of the Mars probe "Amal" (ال امل, meaning ‘Hope’ in Arabic), which was the first in the Arab world and the fifth in the world to successfully enter into orbit around Mars, and the UAE’s first independently developed Earth observation satellite "KhalifaSat". An official from the KAIST Alumni Association said, "We selected the Distinguished International Alumni after evaluating their industrious leadership in promoting various space industry strategies, ranging from the development of Mars probes and Earth observation satellites, as well as lunar exploration, asteroid exploration, and Mars residence plans." (From left) Joo-Sun Choi, President & CEO of Samsung Display Co. Ltd., Jung Goo Cho, the CEO of Green Power Co. Ltd., Jong Seung Park, the President of Agency for Defense Development (ADD), Kyunghyun Cho, Professor of New York University (NYU) Also, four of the Korean graduates, Joo-Sun Choi, the CEO of Samsung Display, Jung Goo Cho, the CEO of Green Power Co. Ltd., Jong Seung Park, the President of Agency for Defense Development (ADD), and Kyunghyun Cho, a Professor of New York University (NYU), were selected as the winners of the “Distinguished Alumni Award”. Mr. Joo-Sun Choi (Electrical and Electronic Engineering, M.S. in 1989, Ph.D. in 1995), the CEO of Samsung Display, led the successful development and mass-production of the world's first ultra-high-definition QD-OLED Displays, and preemptively transformed the structure of business of the industry and has been leading the way in technological innovation. Mr. Jung Goo Cho (Electrical and Electronic Engineering, M.S. in 1988, Ph.D. in 1992), the CEO of Green Power Co. Ltd., developed wireless power technology for the first time in Korea in the early 2000s and applied it to semiconductor/display lines and led the wireless power charging technology in various fields, such as developing KAIST On-Line Electric Vehicles (OLEV) and commercializing the world's first wireless charger for 11kW electric vehicles. Mr. Jong Seung Park (Mechanical Engineering, M.S. in 1988, Ph.D., in 1991), The President of ADD is an expert with abundant science and technology knowledge and organizational management capabilities. He is contributing greatly to national defense and security through science and technology. Mr. Kyunghyun Cho (Computer Science, B.S., in 2009), the Professor of Computer Science and Data Science at NYU, is a world-renowned expert in Artificial Intelligence (AI), advancing the concept of 'Neural Machine Translation' in the field of natural language processing, to make great contributions to AI translation technology and related industries. Chairman Chil-Hee Chung, the 26th Chair of KAIST Alumni Association “As each year goes by, I feel that the influence of KAIST alumni goes beyond science and technology to affect our society as a whole.” He went on to say, “This year, as it was more meaningful to extend the award to honor the international members of our Alums, we look forward to seeing more of our alumni continuing their social and academic endeavors to play an active role in the global stage in taking on the global challenges.” The Ceremony for KAIST Distinguished Alumni and International Alumni Award Honorees will be conducted at the Annual New Year’s Event of KAIST Alumni Association for 2023 to be held on Friday, January 13th, at the Grand InterContinental Seoul Parnas.
KAIST’s unmanned racing car to race in the Indy Autonomous Challenge @ CES 2023 as the only contender representing Asia
- Professor David Hyunchul Shim of the School of Electrical Engineering, is at the Las Vegas Motor Speedway in Las Vegas, Nevada with his students of the Unmanned Systems Research Group (USRG), participating in the Indy Autonomous Challenge (IAC) @ CES as the only Asian team in the race. Photo 1. Nine teams that competed at the first Indy Autonomous Challenge on October 23, 2021. (KAIST team is the right most team in the front row) - The EE USRG team won the slot to race in the IAC @ CES 2023 rightly as the semifinals entree of the IAC @ CES 2022’ held in January of last year - Through the partnership with Hyundai Motor Company, USRG received support to participate in the competition, and is to share the latest developments and trends of the technology with the company researchers - With upgrades from last year, USRG is to race with a high-speed Indy racing car capable of driving up to 300 km/h and the technology developed in the process is to be used in further advancement of the high-speed autonomous vehicle technology of the future. KAIST (President Kwang Hyung Lee) announced on the 5th that it will participate in the “Indy Autonomous Challenge (IAC) @ CES 2023”, an official event of the world's largest electronics and information technology exhibition held every year in Las Vegas, Nevada, of the United States from January 5th to 8th. Photo 2. KAIST Racing Team participating in the Indy Autonomous Challenge @ CES 2023 (Team Leader: Sungwon Na, Team Members: Seongwoo Moon, Hyunwoo Nam, Chanhoe Ryu, Jaeyoung Kang) “IAC @ CES 2023”, which is to be held at the Las Vegas Motor Speedway (LVMS) on January 7, seeks to advance technology developed as the result of last year's competition to share the results of such advanced high-speed autonomous vehicle technology with the public. This competition is the 4th competition following the “Indy Autonomous Challenge (IAC)” held for the first time in Indianapolis, USA on October 23, 2021. At the IAC @ CES 2022 following the first IAC competition, the Unmmaned Systems Research Group (USRG) team led by Professor David Hyunchul Shim advanced to the semifinals out of a total of nine teams and won a spot to participate in CES 2023. As a result, the USRG comes into the challenge as the only Asian team to compete with other teams comprised of students and researchers of American and European backgrounds where the culture of motorsports is more deep-rooted. For CES 2022, Professor David Hyunchul Shim’s research team was able to successfully develop a software that controlled the racing car to comply with the race flags and regulations while going up to 240 km/h all on its on. Photo 3. KAIST Team’s vehicle on Las Vegas Motor Speedway during the IAC @ CES 2022 In the IAC @ CES 2023, the official racing vehicle AV-23, is a converted version of IL-15, the official racing car for Indy 500, fully automated while maintaining the optimal design for high-speed racing, and was upgraded from the last year’s competition taking up the highest speed up to 300 km/h. This year’s competition, will develop on last year’s head-to-head autonomous racing and take the form of the single elimination tournament to have the cars overtake the others without any restrictions on the driving course, which would have the team that constantly drives at the fastest speed will win the competition. Photo 4. KAIST Team’s vehicle overtaking the Italian team, PoliMOVE’s vehicle during one of the race in the IAC @ CES 2022 Professor Shim's team further developed on the CES 2022 certified software to fine tune the external recognition mechanisms and is now focused on precise positioning and driving control technology that factors into maintaining stability even when driving at high speed. Professor Shim's research team won the Autonomous Driving Competition hosted by Hyundai Motor Company in 2021. Starting with this CES 2023 competition, they signed a partnership contract with Hyundai to receive financial support to participate in the CES competition and share the latest developments and trends of autonomous driving technology with Hyundai Motor's research team. During CES 2023, the research team will also participate in other events such as the exhibition by the KAIST racing team at the IAC’s official booth located in the West Hall. Professor David Hyunchul Shim said, “With these competitions being held overseas, there were many difficulties having to keep coming back, but the students took part in it diligently, for which I am deeply grateful. Thanks to their efforts, we were able to continue in this competition, which will be a way to verify the autonomous driving technology that we developed ourselves over the past 13 years, and I highly appreciate that.” “While high-speed autonomous driving technology is a technology that is not yet sought out in Korea, but it can be applied most effectively for long-distance travel in the Korea,” he went on to add. “It has huge advantages in that it does not require constructions for massive infrastructure that costs enormous amount of money such as high-speed rail or urban aviation and with our design, it is minimally affected by weather conditions.” he emphasized. On a different note, the IAC @ CES 2023 is co-hosted by the Consumer Technology Association (CTA) and Energy Systems Network (ESN), the organizers of CES. Last year’s IAC winner, Technische Universität München of Germany, and MIT-PITT-RW, a team of Massachusetts Institute of Technology (Massachusetts), University of Pittsburgh (Pennsylvania), Rochester Institute of Technology (New York), University of Waterloo (Canada), with and the University of Waterloo, along with TII EuroRacing - University of Modena and Reggio Emilia (Italy), Technology Innovation Institute (United Arab Emirates), and five other teams are in the race for the win against KAIST. Photo 5. KAIST Team’s vehicle on the track during the IAC @ CES 2022 The Indy Autonomous Challenge is scheduled to hold its fifth competition at the Monza track in Italy in June 2023 and the sixth competition at CES 2024.
KAIST to showcase a pack of KAIST Start-ups at CES 2023
- KAIST is to run an Exclusive Booth at the Venetian Expo (Hall G) in Eureka Park, at CES 2023, to be held in Las Vegas from Thursday, January 5th through Sunday, the 8th. - Twelve businesses recently put together by KAIST faculty, alumni, and the start-ups given legal usage of KAIST technologies will be showcased. - Out of the participating start-ups, the products by Fluiz and Hills Robotics were selected as the “CES Innovation Award 2023 Honoree”, scoring top in their respective categories. On January 3, KAIST announced that there will be a KAIST booth at Consumer Electronics Show (CES) 2023, the most influential tech event in the world, to be held in Las Vegas from January 3 to 8. At this exclusive corner, KAIST will introduce the technologies of KAIST start-ups over the exhibition period. KAIST first started holding its exclusive booth in CES 2019 with five start-up businesses, following up at CES 2020 with 12 start-ups and at CES 2022 with 10 start-ups. At CES 2023, which would be KAIST’s fourth conference, KAIST will be accompanying 12 businesses including start-ups by the faculty members, alumni, and technology transfer companies that just began their businesses with technologies from their research findings that stands a head above others. To maximize the publicity opportunity, KAIST will support each company’s marketing strategies through cooperation with the Korea International Trade Association (KITA), and provide an opportunity for the school and each startup to create global identity and exhibit the excellence of their technologies at the convention. The following companies will be at the KAIST Booth in Eureka Park: The twelve startups mentioned above aim to achieve global technology commecialization in their respective fields of expertise spanning from eXtended Reality (XR) and gaming, to AI and robotics, vehicle and transport, mobile platform, smart city, autonomous driving, healthcare, internet of thing (IoT), through joint research and development, technology transfer and investment attraction from world’s leading institutions and enterprises. In particular, Fluiz and Hills Robotics won the CES Innovation Award as 2023 Honorees and is expected to attain greater achievements in the future. A staff member from the KAIST Institute of Technology Value Creation said, “The KAIST Showcase for CES 2023 has prepared a new pitching space for each of the companies for their own IR efforts, and we hope that KAIST startups will actively and effectively market their products and technologies while they are at the convention. We hope it will help them utilize their time here to establish their name in presence here which will eventually serve as a good foothold for them and their predecessors to further global commercialization goals.”
KAIST Team Develops Surface-Lighting MicroLED Patch with Significant Melanogenesis Inhibition Effect
A KAIST research team led by Ph.d candidate Jae Hee Lee and Professor Keon Jae Lee from the Department of Materials Science and Engineering has developed a surface-lighting microLED patch for UV-induced melanogenesis inhibition. Melanin is brown or dark pigments existing in the skin, which can be abnormally synthesized by external UV or stress. Since the excessive melanin leads to skin diseases such as spots and freckles, proper treatment is required to return normal skin condition. Recently, LED-based photo-stimulators have been released for skin care, however, their therapeutic effect is still controversial. Since conventional LED stimulators cannot conformally attach to the human skin, distance-induced side effects are caused by light loss and high heat transfer. To achieve effective phototreatment, the LED stimulator needs to be irradiated in contact with the human skin surface, enabling proper and uniform light deliver to the dermis with minimal optical loss. In this work, the research team fabricated skin-attachable surface-lighting microLED (SµLED, 4 × 4 cm2) patch by utilizing a thousand of microLED chips and silica-embedded light diffusion layer. 100 µm-sized LED chips are vertically-interconnected for high flexibility and low heat generation, allowing its long-term operation on the human skin. < Image 1. The overall concept of SµLED patch. a) SµLED patch operated on the human skin. b) Schematic illustration of SµLED patch structure. c) 4 × 4 cm2-sized SµLED patch. d) Schematic illustration of the advantages of SµLED patch such as efficient light delivery, low heat generation, and surface-lighting irradiation. > The research team confirmed melanogenesis inhibition by irradiating the SµLED patch and the conventional LED (CLED) on the artificial human skin and mice dorsal skin. The SµLED-treated groups of human cells and mouse tissues showed minimal epidermal photo-toxicity and consistently effective reduction in synthesized melanin, compared to CLED-treated groups. In addition, significant suppression of proteins/catalysts expression involved in melanin synthesis such as MITF (microphthalmia-associated transcription factor), Melan-A and tyrosinase was verified. < Image 2. The efficacy of melanogenesis inhibition on 3D human skin cells. a). Different irradiation conditions for a-MSH (major factor to stimulate melanin synthesis) treated cells. b) The ratio of pigmented area to total epidermis area. c) Relative variance of melanin level in 1 cm2-sized skin cells. A low variance means that melanin is evenly distributed, and a high variance means that the melanin is irregularly distributed. d) Optical images after in vitro experiments for 12 days. Scale bar, 1cm. e) Histological analysis of 3D skin, showing the greatest reduction in melanin after SµLED irradiation. Scale bar, 20 µm. > < Image 3. The efficacy of melanogenesis inhibition on mouse dorsal skin. a) Optical images of mice dorsal skin after photo-treatment for 20 days. b) Histological analysis of mice dorsal skin. Less brown color means less expression of protein/catalysis involved in melanin synthesis. Scale bar, 50 µm. > Prof. Keon Jae Lee said, “Our inorganic-based SµLED patch has outstanding characteristics in light efficiency, reliability, and durability. The SµLED patch is expected to give a great impact on the cosmetic field by reducing side effects and maximizing phototherapeutic effects.” The core technology of cosmetic SµLED has been transferred to Fronics co., Ltd, founded by Prof. Lee. Fronics is building foundry and equipment for mass production of SµLED masks for whole face cover and plans to release the products in March next year. This paper entitled “Wearable Surface-Lighting Micro-Light-Emitting Diode Patch for Melanogenesis Inhibition” was published in the November 2022 issue of Advanced Healthcare Materials.
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