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A Korean research team develops a new clinical candidate for fatty liver disease
A team of Korean researchers have succeeded in developing a new drug candidate for the treatment of non-alcoholic fatty liver disease (NAFLD) acting on peripheral tissues. To date, there has not been an optimal treatment for non-alcoholic steatohepatitis (NASH), and this discovery is expected to set the grounds for the development of new drugs that can safely suppress both liver fat accumulation and liver fibrosis at the same time. A joint research team led by Professor Jin Hee Ahn from Gwangju Institute of Science and Technology (GIST) and Professor Hail Kim from the KAIST Graduate School of Medical Science and Engineering developed a new chemical that can suppress disease-specific protein (HTR2A) through years of basic research. The team also revealed to have verified its efficacy and safety through preclinical tests (animal tests) at JD Bioscience Inc., a start-up company founded by Professor Ahn. Although NAFLD has a prevalence rate as high as 20-30%, and about 5% of the global adult population suffers from NASH, there are no commercial drugs targeting them to date. NAFLD is a chronic disease that starts from the fatty liver and progresses into steatohepatitis, fibrosis, cirrhosis, and liver cancer. The mortality rate of patients increases with accompanied cardiovascular diseases and liver-related complications, and appropriate treatment in the early stage is hence necessary. < Figure 1. Strategy and history of 5HT2A antagonists. Library and rational design for the development of compound 11c as a potent 5HT2A antagonist. Previous research efforts were discontinued due to limited oral absorption and safety. A therapeutic candidate to overcome this problem was identified and phase 1 clinical trials are currently in progress. > The new synthetic chemical developed by the joint GIST-KAIST research is an innovative drug candidate that shows therapeutic effects on NASH based on a dual action mechanism that inhibits the accumulation of fat in the liver and liver fibrosis by suppressing the serotonin receptor protein 5HT2A. The research team confirmed its therapeutic effects in animal models for NAFLD and NASH, in which hepatic steatosis and liver fibrosis* caused by fat accumulation in the liver were suppressed simultaneously by 50-70%. *fibrosis: stiffening of parts of the liver, also used as a major indicator to track the prognosis of steatosis The research team explained that the material was designed with optimal polarity and lipid affinity to minimize its permeability across the blood-brain barrier. It therefore does not affect the brain, and causes little side effects in the central nervous system (CNS) such as depression and suicidal ideations, while demonstrating excellent inhibition on its target protein present in tissues outside brain (IC50* = 14 nM). The team also demonstrated its superior efficacy in improving liver fibrosis when compared to similar drugs in the phase 3 clinical trial. *IC50 (half maximal inhibitory concentration): the concentration at which a chemical suppresses 50% of a particular biological function < Figure 2. GM-60106 (11c)'s effect on obesity: When GM-60106 was administered to an obese animal model (mice) for 2 months, body weight, body fat mass, and blood sugar were significantly reduced (a-d). In addition, the steatohepatitis level (NAFLD Activity Score) and the expression of genes of the treated mice involved in adipogenesis along with blood/liver fat decreased (e-h) > Based on the pharmacological data obtained through preclinical trials, the team evaluated the effects of the drug on 88 healthy adults as part of their phase 1 clinical trial, where the side effects and the safe dosage of a drug are tested against healthy adults. Results showed no serious side effects and a good level of drug safety. In addition, a preliminary efficacy evaluation on eight adults with steatohepatitis is currently underway. Professor Jin Hee Ahn said, “The aim of this research is to develop a treatment for NASH with little side effects and guaranteed safety by developing a new target. The developed chemical is currently going through phase 1 of the global clinical trial in Australia through JD Bioscience Inc., a bio venture company for innovative drug development.” he added, “The candidate material the research team is currently developing shows not only a high level of safety and preventative effects by suppressing fat accumulation in the liver, but also a direct therapeutic effect on liver fibrosis. This is a strength that distinguishes our material from other competing drugs.” < Figure 3. Efficacy of GM-60106 (11c) on liver fibrosis: When GM-60106 was administered to a steatohepatitis model (mice) for 3 months, the expression of genes associated with tissue fibrosis was significantly reduced (b-c). As a result of a detailed analysis of the tissues of the animal model, it was confirmed that the rate of tissue fibrosis was reduced and the expression rate of genes related to tissue fibrosis and inflammation was also significantly reduced (e-h). > Professor Hail Kim from KAIST said, “Until now, this disease did not have a method of treatment other than weight control, and there has been no attempt to develop a drug that can be used for non-obese patients.” He added, “Through this research, we look forward to the development of various treatment techniques targeting a range of metabolic diseases including NASH that do not affect the weight of the patient.” This study, conducted together by the research teams led by Professor Ahn from GIST and Professor Kim from KAIST, as well as the research team from JD Bioscience Inc., was supported by the Ministry of Science and ICT, and the National New Drug Development Project. The results of this research were published by Nature Communications on January 20. The team also presented the results of their clinical study on the candidate material coded GM-60106 targeting metabolic abnormality-related MASH* at NASH-TAG Conference 2024, which was held in Utah for three days starting on January 4, which was selected as an excellent abstract. *MASH (Metabolic Dysfunction-Associated Steatohepatitis): new replacement term for NASH
World-renowned Soprano Sumi Jo and Broadcom CEO Hock Tan receives honorary doctorate from KAIST
< (From left) Sumi Jo, Distinguished Visiting Professor at the Graduate School of Culture and Technology, and Broadcom President and CEO Hock Tan > KAIST (President Kwang-Hyung Lee) announced that it awarded honorary doctorates to world-renowned soprano Sumi Jo, a distinguished visiting professor at the Graduate School of Culture and Technology, and the President and Chief Executive Officer of Broadcom Inc., Hock Tan, at the graduation ceremony held on the 16th of February, 2024. Professor Sumi Jo, who received an honorary doctorate in science and technology, was appointed as a visiting professor at KAIST Graduate School of Culture and Technology in 2021 and established the "Sumi Jo Performing Arts Research Center" and have been involved in research providing valuable feedback on projects to put on stage performances utilizing AI-orchestrated musical ensemble technology and research on virtual voices using vocal synthesis technology, as well as participating in the demonstration of the technological performance showcased at KAIST. Also, she held a special lecture and a talk concert for KAIST students, sharing her experience as a celebrated soprano on the world stage and having honest conversations with students. KAIST said, “The doctorate is being awarded in recognition of her contributions that is broadening the spectrum of research in the field of science and technology to lead the digital era by suggesting a direction for future science and technology to take led by culture. Also, her significant contribution to promoting necessary internationalization capabilities helps KAIST as it is growing into a world-class university through new academic challenges.” < Professor Sumi Jo (left), who received an honorary doctorate in science and technology, and President Kwang-Hyung Lee > Professor Sumi Jo, who debuted as Gilda in the opera <Rigoletto> in 1986, has performed with world-class conductors such as Herbert von Karajan, Georg Solti, Zubin Mehta, and James Levine. She has released over 40 full-length albums and continues to excel in all areas of vocal performances, including film scores, songs, and musicals. Professor Sumi Jo said, “When I received a proposal from President Kwang-Hyung Lee of KAIST to convey what I experienced and felt on the world stage to students of science at KAIST under the topic of ‘Music and My Life,’ questions started to swirl inside of me.” She continued, “Singing on stage is about ‘expressing,’ and it is a comprehensive artistic process that unfolding the artist’s inner self (expression) and showing it (presentation) in a way that the audience can best feel it through methods such as sound, lighting, and directing. And I realized that, I was singing all my life in an environment where science and technology coexisted with culture and art.” “When I worked with the students here at KAIST, I came to realize that when scientific and technologically talented people are set free to really enjoy their ideas and explore them on their own terms, their insight become sharper and their creativity become richer,” she said. She went on to add, “I am proud to be able to join the graduates at the ceremony and would like to express my gratitude for awarding me the honorary doctorate.” < (From left) President Hock Tan, who received the honorary doctorate in engineering, Mrs. Lya Trung Tan, and President Kwang-Hyung Lee > Hock Tan received an honorary doctorate in engineering. He is a highly successful businessman who demonstrated entrepreneurship based on a profound understanding of science and technology, which transformed Broadcom into a global enterprise in technology that provides semiconductor and software solutions. Broadcom has achieved advancement and technological innovation in the semiconductor industry tailored to computer and telecommunication networks, and is evaluated as having played a major role in bringing about the digital transformation movement that is now encompassing the global communities. Tan attributes the secret to his success to ‘the considerate decision made by the university to award him the scholarship which enabled him to pursue his degree’ and ‘the great team members working with him’..’ Also, he is well-known as a person who considers giving back to society his most important mission. To support effective medical treatment and identification of the cause of autism, Tan has made large donations to MIT and Harvard University since 2017 several times, and during the COVID-19 pandemic, he reinforced his support to improve the treatment of workers at community medical institutions and non-profit organizations. He also founded the Broadcom Foundation, which supports science, technology, engineering, and mathematics (STEM) education programs for students in and outside the United States. KAIST said, “We are awarding CEO Hock Tan the honorary doctorate in recognition of his contribution to KAIST’s emergence as a world-class university, as he emphasized the importance of convergence research and internationalization of KAIST during his time serving as an overseas member of the KAIST President's Advisory Council from 2006 to 2013, while providing policy advices built on his experiences of innovations from various parts around the world.” Tan emphasized, “KAIST has been vital to Korea’s advancement in the global economy. (KAIST) remains a source of technological innovation,” and that, “It is truly an honor to be recognized by an institution with such a distinguished record of excellence in science, engineering and research.” President Kwang-Hyung Lee said, “Professor Sumi Jo’s exploration into the future of performing arts through science and technology helps to expand KAIST’s scope and enhance our creative capabilities, while the dedication and humane efforts Hock Tan demonstrates as he contributes to digital innovation through corporate management and engages in various social contribution activities serves as a superb example to all members of KAIST.” He continued, “These two have lived out the values of challenge and innovation and became examples for many, and we are very pleased to welcome them as the newest members of the KAIST family. On behalf of all members of KAIST, I deliver our sincere congratulations.”
Professor Sukyung Park Named Presidential Science and Technology Adviser
Professor Sukyung Park from the Department of Mechanical Engineering was appointed as the science and technology adviser to the President Jae-in Moon on May 4. Professor Park, at the age of 47, became the youngest member of the president’s senior aide team at Chong Wa Dae. A Chong Wa Dae spokesman said on May 4 while announcing the appointment, “Professor Park, a talent with a great deal of policymaking participation in science and technology, will contribute to accelerating the government’s push for science and technology innovation, especially in the information and communications technology (ICT) sector.” Professor Park joined KAIST in 2004 as the first female professor of mechanical engineering. She is a biomechanics expert who has conducted extensive research on biometric mechanical behaviors. Professor Park is also a member of the KAIST Board of Trustees. Before that, she served as a senior researcher at the Korea Institute of Machinery and Materials (KIMM) as well as a member of the Presidential Advisory Council on Science and Technology. After graduating from Seoul Science High School as the first ever two-year graduate, Professor Park earned a bachelor and master’s degrees in mechanical engineering at KAIST. She then finished her Ph.D. from the University of Michigan. (END)
Former Minister of Science and Technology Woo Sik Kim Elected as New Chairman of Board of Trustees
Dr. Woo Sik Kim, former Minister of Science and Technology and Deputy Prime Minister, was elected as the new chairman of the KAIST Board of Trustees on March 26. Dr. Kim will succeed Chairman Jang-Mu Lee, whose three-year term expired last month. Dr. Kim is a chemical engineering professor who spent most of his academic career at Yonsei University from 1968. In 2000, he held the office of president of Yonsei University for four years before moving to the Presidential Office of President Roh Moo-Hyun as his chief of staff in 2004. After serving in the Blue House for two years, he served as the Minister of Science and Technology from 2006 to 2008. An emeritus fellow of the National Academy of Engineering of Korea (NAEK), Chairman Kim also taught at KAIST as an invited distinguished professor from 2008 to 2010. He is currently the chairman of the Creativity Engineering Institute (CEI). (END)
What Fuels a “Domino Effect” in Cancer Drug Resistance?
KAIST researchers have identified mechanisms that relay prior acquired resistance to the first-line chemotherapy to the second-line targeted therapy, fueling a “domino effect” in cancer drug resistance. Their study featured in the February 7 edition of Science Advances suggests a new strategy for improving the second-line setting of cancer treatment for patients who showed resistance to anti-cancer drugs. Resistance to cancer drugs is often managed in the clinic by chemotherapy and targeted therapy. Unlike chemotherapy that works by repressing fast-proliferating cells, targeted therapy blocks a single oncogenic pathway to halt tumor growth. In many cases, targeted therapy is engaged as a maintenance therapy or employed in the second-line after front-line chemotherapy. A team of researchers led by Professor Yoosik Kim from the Department of Chemical and Biomolecular Engineering and the KAIST Institute for Health Science and Technology (KIHST) has discovered an unexpected resistance signature that occurs between chemotherapy and targeted therapy. The team further identified a set of integrated mechanisms that promotes this kind of sequential therapy resistance. “There have been multiple clinical accounts reflecting that targeted therapies tend to be least successful in patients who have exhausted all standard treatments,” said the first author of the paper Mark Borris D. Aldonza. He continued, “These accounts ignited our hypothesis that failed responses to some chemotherapies might speed up the evolution of resistance to other drugs, particularly those with specific targets.” Aldonza and his colleagues extracted large amounts of drug-resistance information from the open-source database the Genomics of Drug Sensitivity in Cancer (GDSC), which contains thousands of drug response data entries from various human cancer cell lines. Their big data analysis revealed that cancer cell lines resistant to chemotherapies classified as anti-mitotic drugs (AMDs), toxins that inhibit overacting cell division, are also resistant to a class of targeted therapies called epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). In all of the cancer types analyzed, more than 84 percent of those resistant to AMDs, representatively ‘paclitaxel’, were also resistant to at least nine EGFR-TKIs. In lung, pancreatic, and breast cancers where paclitaxel is often used as a first-line, standard-of-care regimen, greater than 92 percent showed resistance to EGFR-TKIs. Professor Kim said, “It is surprising to see that such collateral resistance can occur specifically between two chemically different classes of drugs.” To figure out how failed responses to paclitaxel leads to resistance to EGFR-TKIs, the team validated co-resistance signatures that they found in the database by generating and analyzing a subset of slow-doubling, paclitaxel-resistant cancer models called ‘persisters’. The results demonstrated that paclitaxel-resistant cancers remodel their stress response by first becoming more stem cell-like, evolving the ability to self-renew to adapt to more stressful conditions like drug exposures. More surprisingly, when the researchers characterized the metabolic state of the cells, EGFR-TKI persisters derived from paclitaxel-resistant cancer cells showed high dependencies to energy-producing processes such as glycolysis and glutaminolysis. “We found that, without an energy stimulus like glucose, these cells transform to becoming more senescent, a characteristic of cells that have arrested cell division. However, this senescence is controlled by stem cell factors, which the paclitaxel-resistant cancers use to escape from this arrested state given a favorable condition to re-grow,” said Aldonza. Professor Kim explained, “Before this research, there was no reason to expect that acquiring the cancer stem cell phenotype that dramatically leads to a cascade of changes in cellular states affecting metabolism and cell death is linked with drug-specific sequential resistance between two classes of therapies.” He added, “The expansion of our work to other working models of drug resistance in a much more clinically-relevant setting, perhaps in clinical trials, will take on increasing importance, as sequential treatment strategies will continue to be adapted to various forms of anti-cancer therapy regimens.” This study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF-2016R1C1B2009886), and the KAIST Future Systems Healthcare Project (KAISTHEALTHCARE42) funded by the Korean Ministry of Science and ICT (MSIT). Undergraduate student Aldonza participated in this research project and presented the findings as the lead author as part of the Undergraduate Research Participation (URP) Program at KAIST. < Figure 1. Schematic overview of the study. > < Figure 2. Big data analysis revealing co-resistance signatures between classes of anti-cancer drugs. > Publication: Aldonza et al. (2020) Prior acquired resistance to paclitaxel relays diverse EGFR-targeted therapy persistence mechanisms. Science Advances, Vol. 6, No. 6, eaav7416. Available online at http://dx.doi.org/10.1126/sciadv.aav7416 Profile: Prof. Yoosik Kim, MA, PhD email@example.com https://qcbio.kaist.ac.kr/ Assistant Professor Bio Network Analysis Laboratory Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology (KAIST) http://kaist.ac.kr Daejeon, Republic of Korea Profile: Mark Borris D. Aldonza firstname.lastname@example.org Undergraduate Student Department of Biological Sciences Korea Advanced Institute of Science and Technology (KAIST) http://kaist.ac.kr Daejeon, Republic of Korea (END)
Professor Sung Yong Kim Elected as the Chair of PICES MONITOR
< Professor Sung Yong Kim > Professor Sung Yong Kim from the Department of Mechanical Engineering was elected as the chair of the Technical Committee on Monitoring (MONITOR) of the North Pacific Marine Science Organization (PICES). PICES is an intergovernmental marine science organization that was established in 1992 through a collaboration between six North Pacific nations including South Korea, Russia, the United States, Japan, China, and Canada to exchange and discuss research on the Pacific waters. Its headquarters is located in Canada and the organization consists of seven affiliated maritime science and marine technology committees. Professor Kim was elected as the chair of the technical committee that focuses on monitoring and will be part of the Science Board as an ex-officio member. His term will last three years from November 2019. Professor Kim was recognized for his academic excellence, expertise, and leadership among oceanographers both domestically and internationally. Professor Kim will also participate as an academia civilian committee member of the Maritime and Fisheries Science and Technology Committee under the Korean Ministry of Oceans and Fisheries for two years from December 18, 2019. He stated, “I will give my full efforts to broaden Korean oceanography research by participating in maritime leadership positions at home and abroad, and help South Korea become a maritime powerhouse.” (END)
Professor Shin-Hyun Kim Receives the Young Scientist Award
Professor Shin-Hyun Kim from the Department of Chemical and Biomolecular Engineering received the Young Scientist Award from the Korean Academy of Science and Technology. The Young Scientist Award is presented to a promising young Korean scientist under the age of 40 who shows significant potential, passion, and remarkable achievement. Professor Kim was lauded for his research of intelligent soft materials. By applying his research, he developed a capsule sensor material that can not only be used for sensors, but also for displays, color aesthetics, anti-counterfeit technology, residual drug detection, and more. The award ceremony took place on December 14 at the Gwacheon National Science Museum. The Korean minister of Science and ICT delivered words of encouragement, reminding everyone that “the driving force behind creative performance of scientists is the provision of continuous support.” He added, “Researchers of Korea deserve greater public attention and support.” (END)
New Members of KAST 2020
< Professor Zong-Tae Bae (Left) and Professor Sang Ouk Kim (Right) > Professor Zong-Tae Bae from the School of Management Engineering and Professor Sang Ouk Kim from the Department of Materials Science and Engineering became new fellows of the Korean Academy of Science and Technology (KAST) along with 22 other scientists in Korea. On November 22, KAST announced 24 new members for the year 2020. This includes seven scientists from the field of natural sciences, six from engineering, four from medical sciences, another four from policy research, and three from agriculture and fishery. The new fellows will begin their term from January next year, and their fellowships wll be conferred during the KAST’s New Year Reception to be held on January 14 in Seoul. (END)
Two Alumni Win the Korea Best Scientist and Technologist Awards
Vice Chairman Ki-Nam Kim (Left) and Distinguished Professor Sukbok Chang (Right) <ⓒ Photo by MSIT and KOFST> Distinguished KAIST Professor Sukbok Chang from the Department of Chemistry and Vice Chairman Ki-Nam Kim of Samsung Electronics were selected as the winners of the “2019 Korea Best Scientist and Technologist Awards” by the Ministry of Science and ICT (MSIT) and the Korean Federation of Science and Technology Societies (KOFST). The awards, which were first handed out in 2003, are the highest honor bestowed to the two most outstanding scientists in Korea every year, and this year’s awardees are of greater significance as they are both KAIST alumni. Professor Chang was recognized for his pioneering achievements and lifetime contributions to the development of carbon-hydrogen activation strategies, especially for carbon-carbon, carbon-nitrogen, and carbon-oxygen formations. His research group has also been actively involved in the development of highly selective catalytic systems allowing the controlled defunctionalization of bio-derived platform substrates under mild conditions, and opening a new avenue for the utilization of biomass-derived platform chemicals. The results of his study have been introduced worldwide through many prestigious journals including Science, Nature Chemistry, and Nature Catalysis, making him one of the world's top 1% researchers by the number of references made to his papers by his peers over four consecutive years from 2015 to 2018. Vice Chairman Kim, who received his M.E. degree from KAIST’s School of Electrical Engineering in 1983, has been credited with playing a leading role in the development of system semiconductors. The awards were conferred on July 4 at the opening ceremony of the 2019 Korea Science and Technology Annual Meeting. (END)
New Members of KAST and Y-KAST 2019
(Professor Eui-Cheol Shin from the Graduate School of Medical Science and Engineering) Professor Eui-Cheol Shin from the Graduate School of Medical Science and Engineering became a new fellow of the Korean Academy of Science and Technology (KAST) along with 25 other scientists in Korea. He is one of the top virus immunologists in Korea and has published a review article in Nature Reviews Immunology. Meanwhile KAST selected and announced 26 young scientists under the age 43 who have shown great potential and the creativity to carry out next-generation research. The list of Y-KAST (Young Korean Academy of Science and Technology) includes six KAIST professors: Professor Ji Oon Lee from the Department of Mathematical Sciences, Professor Mi Hee Lim from the Department of Chemistry, Professor Shin-Hyun Kim from the Department of Chemical and Biomolecular Engineering, Professor Jung-Ryul Lee from the Department of Aerospace Engineering, Professor Hyunjoo Jenny Lee from the School of Electrical Engineering, and Professor Yeon Sik Jung from the Department of Materials Science and Engineering. KAST conferred their fellowships and Y-KAST membership during the New Year Reception.
Scientist of October, Professor Haeshin Lee
(Professor Haeshin Lee from the Department of Chemistry) Professor Haeshin Lee from the Department of Chemistry received the ‘Science and Technology Award of October’ from the Ministry of Science and ICT and the National Research Foundation of Korea for his contribution to developing an antibleeding injection needle. This novel outcome will fundamentally prevent the problem of secondary infections of AIDS, Ebola and Hepatitis viruses transmitting from patients to medical teams. This needle’s surface is coated with hemostatic materials. Its concept is simple and the key to this technology is to make materials that are firmly coated on the needle so that they can endure frictional force when being injected into skin and blood vessels. Moreover, the materials should be adhesive to skin and the interior of blood vessels, but harmless to humans. Professor Lee found a solution from natural polymer ingredients. Catecholamine can be found in mussels. Professor Lee conjugated catechol groups on the chitosan backbone. He applied this mussel-inspired adhesive polymer Chitosan-catechol, which immediately forms an adhesive layer with blood, as a bioadhesion for the antibleeding injection needle. Professor Lee said, “Chitosan-catechol, which copies the adhesive mechanism of mussels, shows high solubility in physiological saline as well as great mucoadhesion. Hence, it is perfectly suitable for coating the injection needle. Combining it with proteins allows for efficient drug delivery to the heart, which is a challenging injection location, so it will be also useful for treating incurable heart disease.”
KAISTians Receive Future Ocean Science and Technology Awards
(From left: PhD candidates Minseok Kang and Junkeon Ahn) PhD candidates Minseok Kang and Junkeon Ahn from the Department of Mechanical Engineering received Future Ocean Science and Technology Awards from the Korean Association of Ocean Science and Technology Societies (KAOSTS). Since 2017, KAOSTS has conferred this award upon graduate students who have published outstanding papers on ocean science and technology in order to encourage young researchers in this area. Kang published ‘Ship block assembly sequence planning considering productivity and welding deformation’ in Naval Architecture and Ocean Engineering in which he proposed an assembly sequence planning method for block assemblies that considers the geometric characteristics of blocks to determine feasible assembly sequences as well as assembly process and productivity factors. Ahn published ‘Fuzzy-based FMEA of hybrid MCFC and gas turbine system for marine propulsion’ in Power Sources. In this research, he conducted a study proposing a fuzzy-based failure mode and effect analysis (FMEA) for a hybrid molten carbonate fuel cell and gas turbine system for liquefied hydrogen tankers.
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