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Researchers Present a Microbial Strain Capable of Massive Succinic Acid Production
A research team led by Distinguished Professor Sang Yup Lee reported the production of a microbial strain capable of the massive production of succinic acid with the highest production efficiency to date. This strategy of integrating systems metabolic engineering with enzyme engineering will be useful for the production of industrially competitive bio-based chemicals. Their strategy was described in Nature Communications on April 23. The bio-based production of industrial chemicals from renewable non-food biomass has become increasingly important as a sustainable substitute for conventional petroleum-based production processes relying on fossil resources. Here, systems metabolic engineering, which is the key component for biorefinery technology, is utilized to effectively engineer the complex metabolic pathways of microorganisms to enable the efficient production of industrial chemicals. Succinic acid, a four-carbon dicarboxylic acid, is one of the most promising platform chemicals serving as a precursor for industrially important chemicals. Among microorganisms producing succinic acid, Mannheimia succiniciproducens has been proven to be one of the best strains for succinic acid production. The research team has developed a bio-based succinic acid production technology using the M. succiniciproducens strain isolated from the rumen of Korean cow for over 20 years and succeeded in developing a strain capable of producing succinic acid with the highest production efficiency. They carried out systems metabolic engineering to optimize the succinic acid production pathway of the M. succiniciproducens strain by determining the crystal structure of key enzymes important for succinic acid production and performing protein engineering to develop enzymes with better catalytic performance. As a result, 134 g per liter of succinic acid was produced from the fermentation of an engineered strain using glucose, glycerol, and carbon dioxide. They were able to achieve 21 g per liter per hour of succinic acid production, which is one of the key factors determining the economic feasibility of the overall production process. This is the world’s best succinic acid production efficiency reported to date. Previous production methods averaged 1~3 g per liter per hour. Distinguished professor Sang Yup Lee explained that his team’s work will significantly contribute to transforming the current petrochemical-based industry into an eco-friendly bio-based one. “Our research on the highly efficient bio-based production of succinic acid from renewable non-food resources and carbon dioxide has provided a basis for reducing our strong dependence on fossil resources, which is the main cause of the environmental crisis,” Professor Lee said. This work was supported by the Technology Development Program to Solve Climate Changes via Systems Metabolic Engineering for Biorefineries and the C1 Gas Refinery Program from the Ministry of Science and ICT through the National Research Foundation of Korea.
2020.05.06
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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 ysyoosik@kaist.ac.kr 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 borris@kaist.ac.kr Undergraduate Student Department of Biological Sciences Korea Advanced Institute of Science and Technology (KAIST) http://kaist.ac.kr Daejeon, Republic of Korea (END)
2020.02.10
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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)
2019.12.21
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Tungsten Suboxide Improves the Efficiency of Platinum in Hydrogen Production
< PhD Candidate Jinkyu Park and Professor Jinwoo Lee > Researchers presented a new strategy for enhancing catalytic activity using tungsten suboxide as a single-atom catalyst (SAC). This strategy, which significantly improves hydrogen evolution reaction (HER) in metal platinum (pt) by 16.3 times, sheds light on the development of new electrochemical catalyst technologies. Hydrogen has been touted as a promising alternative to fossil fuels. However, most of the conventional industrial hydrogen production methods come with environmental issues, releasing significant amounts of carbon dioxide and greenhouse gases. Electrochemical water splitting is considered a potential approach for clean hydrogen production. Pt is one of the most commonly used catalysts to improve HER performance in electrochemical water splitting, but the high cost and scarcity of Pt remain key obstacles to mass commercial applications. SACs, where all metal species are individually dispersed on a desired support material, have been identified as one way to reduce the amount of Pt usage, as they offer the maximum number of surface exposed Pt atoms. Inspired by earlier studies, which mainly focused on SACs supported by carbon-based materials, a KAIST research team led by Professor Jinwoo Lee from the Department of Chemical and Biomolecular Engineering investigated the influence of support materials on the performance of SACs. Professor Lee and his researchers suggested mesoporous tungsten suboxide as a new support material for atomically dispersed Pt, as this was expected to provide high electronic conductivity and have a synergetic effect with Pt. They compared the performance of single-atom Pt supported by carbon and tungsten suboxide respectively. The results revealed that the support effect occurred with tungsten suboxide, in which the mass activity of a single-atom Pt supported by tungsten suboxide was 2.1 times greater than that of single-atom Pt supported by carbon, and 16.3 times higher than that of Pt nanoparticles supported by carbon. The team indicated a change in the electronic structure of Pt via charge transfer from tungsten suboxide to Pt. This phenomenon was reported as a result of strong metal-support interaction between Pt and tungsten suboxide. HER performance can be improved not only by changing the electronic structure of the supported metal, but also by inducing another support effect, the spillover effect, the research group reported. Hydrogen spillover is a phenomenon where adsorbed hydrogen migrates from one surface to another, and it occurs more easily as the Pt size becomes smaller. The researchers compared the performance of single-atom Pt and Pt nanoparticles supported by tungsten suboxide. The single-atom Pt supported by tungsten suboxide exhibited a higher degree of hydrogen spillover phenomenon, which enhanced the Pt mass activity for hydrogen evolution up to 10.7 times compared to Pt nanoparticles supported by tungsten suboxide. Professor Lee said, “Choosing the right support material is important for improving electrocatalysis in hydrogen production. The tungsten suboxide catalyst we used to support Pt in our study implies that interactions between the well-matched metal and support can drastically enhance the efficiency of the process.” This research was supported by the Ministry of Science and ICT and introduced in the International Edition of the German journal Angewandte Chemie. Figure. Schematic representation of hydrogen evolution reaction (HER) of pseudo single-atom Pt supported by tungsten suboxide -Publication Jinkyu Park, Dr. Seonggyu Lee, Hee-Eun Kim, Ara Cho, Seongbeen Kim, Dr. Youngjin Ye, Prof. Jeong Woo Han, Prof. Hyunjoo Lee, Dr. Jong Hyun Jang, and Prof. Jinwoo Lee. 2019. Investigation of the Support Effect in Atomically Dispersed Pt on WO3−x for Utilization of Pt in the Hydrogen Evolution Reaction. International Edition of Angewandte Chemie. Volume No. 58. Issue No. 45. 6 pages. https://doi.org/10.1002/anie.201908122 -ProfileProfessor Jinwoo LeeConvergence of Energy and Nano Science Laboratoryhttp://cens.kaist.ac.kr Department of Chemical and Biomolecular EngineeringKAIST
2019.10.28
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Professor Hyun Gyu Park Appointed as Associate Editor for Biosensors and Bioelectronics
Professor Hyun Gyu Park from the Department of Chemical and Biomolecular Engineering was appointed as an associate editor for Biosensors and Bioelectronics, an international journal published by Elsevier. Biosensors and Bioelectronics is one of the top SCI journals in the fields of chemistry and analytical science (IF 9.518 as of 2018). Professor Park was recognized and appointed as the associate editor for this journal due to his outstanding research achievements in the fields of nucleic acid engineering, biosensors, and nanobiotechnology. Professor Park will serve as the associate editor from this October until December 2021. (END)
2019.10.01
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Distinguished Professor Sang Yup Lee Honored with the 23rd NAEK Award
(Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering) Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering was honored to be the laureate of the 23rd NAEK Award. The NAEK (National Academy of Engineering of Korea) Award was instituted in 1997 to honor and recognize engineers who have made significant contributions to the development of the engineering and technology field at universities, industries, and institutions. Every year, it is conferred to only one person who has achieved original and world-leading research that has led to national development. Distinguished Professor Lee is a pioneering scholar of the field of systems metabolic engineering and he was recognized for his significant achievements in the biochemical industry by developing novel microbial bioprocesses. In particular, he is globally renowned for biological plastic synthesis, making or decomposing polymers with microorganisms instead of using fossil resources. He has produced numerous high-quality research breakthroughs in metabolic and systems engineering. In 2016, he produced an easily degradable plastic with Escherichia coli (E. coli). In 2018, he successfully produced aromatic polyesters, the main material for PET (poly ethylene terephthalate) from E. coli strains. He also identified microorganism structures for PET degradation and improved its degradability with a novel variant. His research was ranked number one in the research and development division of Top Ten Science and Technology News 2018 announced by Korean Federation of Science & Technology Societies. He is one of highly cited researchers (HCR) ranked in the top 1% by citations for their field by the Clarivate Analytics.
2019.03.21
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Distinguished Professor Lee Re-Appointed As Co-Chair of the Global Future Council on Biotechnology
(Distinguished Professor Sang Yup Lee) Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering was re-appointed as the co-chair of the Global Future Council on Biotechnology at the World Economic Forum during the annual GFC meeting in Dubai, UAE last week. Elizabeth O’Day, founder and CEO of Olaris Therapeutics, will co-chair the council with him for two years. Professor Lee served as the inaugural co-chair of the council for two years from 2016 with Professor Feng Zhang from the Broad Institute of MIT and Harvard. The World Economic Forum’s Global Future Councils on Biotechnology is comprised of 14 members and aims to identify policy opportunities to help accelerate new biotechnological discoveries and applications while guiding dialogue with consumers about their implications. Professor Lee, who has made significant research breakthroughs in the field of systems metabolic engineering, received the George Washington Carver Award, the PV Danckwerts Memorial Lecture Award, and the Eni Award this year.
2018.11.19
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Distinguished Professor Sang Yup Lee Announced as the Eni Award Recipient
(Distinguished Professor Sang Yup Lee) Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering will be awarded the 2018 Eni Advanced Environmental Solutions Prize in recognition of his innovations in the fields of energy and environment. The award ceremony will take place at the Quirinal Palace, the official residence of Italian President Sergio Mattarella, who will also be attending on October 22. Eni, an Italian multinational energy corporation established the Eni Award in 2008 to promote technological and research innovation of efficient and sustainable energy resources. The Advanced Environmental Solutions Prize is one of the three categories of the Eni Award. The other two categories are Energy Transition and Energy Frontiers. The Award for Advanced Environmental Solutions recognizes a researcher or group of scientists that has achieved internationally significant R&D results in the field of environmental protection and recovery. The Eni Award is referred to as the Nobel Award in the fields of energy and environment. Professor Lee, a pioneering leader in systems metabolic engineering was honored with the award for his developing engineered bacteria to produce chemical products, fuels, and non-food biomass materials sustainably and with a low environmental impact. He has leveraged the technology to develop microbial bioprocesses for the sustainable and environmentally friendly production of chemicals, fuels, and materials from non-food renewable biomass. The award committee said that they considered the following elements in assessing Professor Lee’s achievement: the scientific relevance and the research innovation level; the impact on the energy system in terms of sustainability as well as fairer and broader access to energy; and the adequacy between technological and economic aspects. Professor Lee, who already won two other distinguished prizes such as the George Washington Carver Award and the PV Danckwerts Memorial Lecture Award this year, said, “I am so glad that the international academic community as well as global industry leaders came to recognize our work that our students and research team has made for decades.” Dr. Lee’s lab has been producing a lot of chemicals in environmentally friendly ways. Among them, many were biologically produced for the first time and some of these processes have been already commercialized. “We will continue to strive for research outcomes with two objectives: First, to develop bio-based processes suitable for sustainable chemical industry. The other is to contribute to the human healthcare system through development of platform technologies integrating medicine and nutrition,” he added.
2018.09.12
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Distinguished Professor Lee Receives 2018 George Washington Carver Award
(Distinguished Professor Lee) Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering will become the 11th recipient of the George Washington Carver Award. The award ceremony will be held during the 2018 Biotechnology Innovation Organization (BIO) World Congress on Industrial Biotechnology from July 16 through 19 at the Pennsylvania Convention Center in Philadelphia. The annual Carver award recognizes an individual who has made a significant contribution to building the bio-based economy by applying industrial biotechnology to create environmentally sustainable products. It serves as a lasting memorial to the original vision of George Washington Carver who, over a century ago, pioneered bio-based products, materials, and energy derived from renewable agricultural feedstock. Previous recipients include the founder and CEO of POET Jeff Broin, the CEO of DuPont Ellen Kullman, and Professor Gregory Stephanopoulos at MIT. Professor Lee is a pioneering scholar of systems metabolic engineering, leveraging technology to develop microbial bioprocesses for the sustainable and environment-friendly production of chemicals, fuels, and materials from non-food renewable biomass. He also serves as the dean of the multi-and interdisciplinary research center hub, KAIST Institute.Through his work, Professor Lee has garnered countless achievements, including being one of only 13 people in the world elected as a foreign member of both the National Academy of Sciences USA and the National Academy of Engineering USA. He has actively promoted the importance of industrial biotechnology through engagement with the public, policymakers, and decision makers around the world. He currently serves as the co-chairman of the Global Future Council on Biotechnology for the World Economic Forum and served as the Chairman of the Emerging Technologies Council and Biotechnology Council for the World Economic Forum. Upon the award announcement, Dr. Brent Erickson, executive vice president of BIO’s Industrial & Environmental Section lauded Professor Lee’s achievement, saying “Dr. Lee has advanced the bio-based economy by developing innovative products and processes that are sustainable and environmentally friendly. In doing so, he has become a leader in advocating on the importance of industrial biotechnology. His contributions to the advancement of the industry are a continuation of the legacy left behind by George Washington Carver.” Professor Lee thanked his research team who has worked together for the past few decades, adding, “Industrial biotechnology is becoming increasingly important to help achieve the UN’s Sustainable Development Goals. We should continue to work together to advance the field and establish a solid foundation for the sustainable future.” The George Washington Carver Award is sponsored by the Iowa Biotechnology Association. Joe Hrdlicka, executive director of the Iowa Biotechnology Association, said, “Dr. Sang Yup Lee’s significant contributions to the advancement of industrial biotechnology make him the perfect recipient for the George Washington Carver Award. Having published more than 575 peer-reviewed papers, contributed to 82 books, and holding 636 patents, the culmination of Dr. Lee’s work has led to the establishment of sustainable systems for bio-based production of chemicals, fuels, and materials, thus reducing environmental impact and improving quality of life for all.”
2018.07.12
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P.V. Danckwerts Memorial Lecture Awards Distinguished Professor Lee
(Distinguished Professor Sang Yup Lee) Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering was selected as the awardee of the 2018 P.V. Danckwerts Memorial Lecture. Professor Lee was named the recipient in recognition of his distinguished achievements developing innovative eco-friendly and sustainable chemical materials by applying metabolic engineering. The award is co-sponsored by the Chemical Engineering Science, the Institute of Chemical Engineers, the American Institute of Chemical Engineers, and the European Federation of Chemical Engineering. The award ceremony and Professor Lee’s lecture will be held at the annual meeting of the American Institute of Chemical Engineers in October in Pittsburgh, PA in the US. He will give a lecture titled “Biotechnology to Help Achieve the UN’s Sustainable Development Goals.” The P.V. Danckwerts Lecture was established in 1985 in honor of Professor Peter V. Danckwerts at the University of Cambridge who made significant contributions to the chemical engineering field. Professor Danckwerts served as executive editor of the Chemical Engineering Science and the president of the Institute of Chemical Engineers. Professor Lee, currently the dean of KAIST Institutes, a multi-and interdisciplinary convergence research center, is taking the lead in biotechnology, especially in the field of metabolic engineering. Professor Lee’s research team’s novel approaches have been gaining notable attention in the sustainable chemical engineering field and future health care innovations. His team recently presented research on drug-drug and drug-food interactions by using AI, a recombinant E.coli strain that biosynthesizes 60 different nanomaterials covering 35 elements on the periodic table, bio-degradable aromatic polymer’s enzyme production, and a molecular mechanism for PET degradation. With this award, Professor Lee joined other prominent recipients including Dr. Neal Amundson at the University of Houston, the late Professor Octave Levenspiel at Oregon State University, and Professor Rutherford Aris at the University of Minnesota. Professor Lee is the second Asian recipient, following Dr. Mooson Kwauk at the Institute of Process Engineering of the Chinese Academy of Sciences who won the lecture award in 1989.
2018.06.18
View 5911
Professor Emeritus Jung Ki Park Won the IBA Technology Award 2018
(Professor Emeritus Jung Ki Park) Professor Emeritus Jung Ki Park from the Department of Chemical and Biomolecular Engineering received the IBA Technology Award from the International Battery Association (IBA). IBA 2018 was held from March 11 to 16 on Jeju Island, which was the first time it was hosted in Korea. The conference was an excellent opportunity to let the world know the level of the Korean rechargeable battery industry and its technology. Professor Park delivered his keynote speech titled Advances in Lithium Batteries in Korea at the conference and received the IBA Technology Award as the first Korean recipient. Professor Park is a world-renowned scholar who was a groundbreaker in the rechargeable battery industry. He was recognized by the IBA Award Committee for his contributions carrying out research and development, fostering competent people, and enhancing the lithium rechargeable battery industry in Korea over the last 30 years. Professor Park said, “It is my great honor to receive this award, which is the best international award in the field of rechargeable batteries. I would like to share this with my colleagues and students. As competition in the rechargeable industry intensifies, systemic cooperation among industries, academia, and government is needed for the continued development of the battery industry in Korea.
2018.03.19
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Distinguished Professor Sang Yup Lee Named NAI Fellow
(Distinguished Professor Sang Yup Lee) Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering was named to the National Academy of Inventors in the US. He is the first Korean scholar ever elected as a NAI fellow. The NAI is a non-profit member organization with over 4,000 individual inventors and fellows spanning more than 250 institutions worldwide. It is comprised of universities as well as governmental and non-profit research institutes. The academy was founded in 2010 to recognize and encourage inventors with patents from the US Patent and Trademark Office. So far, 575 fellows from 229 institutions have been elected. The academy said Professor Lee has been recognized for fellowship induction as he has demonstrated a highly prolific spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on quality of life, economic development, and the welfare of society. Distinguished Professor Lee, a pioneering researcher and scholar in the field of systems metabolic engineering, was ranked in the top 1% of highly cited researchers (HCR) this year. Over the past 11 years, he published more than 130,000 articles in prestigious journals around the world. He has been cited more than 34,000 times since he started working at KAIST in 1994. He is also the first Korean ever elected to both the National Academy of Sciences (NAS) and the National Academy of Engineering (NAE) in the US, becoming the one of 13 foreign scholars in the world holding two prestigious institutions’ fellowships. Dr. Lee is currently the dean of KAIST Institutes, the world-leading institute for multi and interdisciplinary research. He is also serving as co-chair of the Global Council on Biotechnology and is a member of the Global Future Council on the Fourth Industrial Revolution at the World Economic Forum.
2017.12.13
View 8960
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