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Early Genome Catastrophes Can Cause Non-Smoking Lung Cancer
Some teenagers harbor catastrophic changes to their genomes that can lead to lung cancer later on in life, even if they never smoke (Professor Young Seok Ju at the Graduate School of Medical Science and Engineering) Catastrophic rearrangements in the genome occurring as early as childhood and adolescence can lead to the development of lung cancer in later years in non-smokers. This finding, published in Cell, helps explain how some non-smoking-related lung cancers develop. Researchers at KAIST, Seoul National University and their collaborators confirmed that gene fusions in non-smokers mostly occur early on, sometimes as early as childhood or adolescence, and on average about three decades before cancer is diagnosed. The study showed that these mutant lung cells, harboring oncogenic seeds, remain dormant for several decades until a number of further mutations accumulate sufficiently for progression into cancer. This is the first study to reveal the landscape of genome structural variations in lung adenocarcinoma. Lung cancer is the leading cause of cancer-related deaths worldwide, and lung adenocarcinoma is its most common type. Most lung adenocarcinomas are associated with chronic smoking, but about a fourth develop in non-smokers. Precisely what happens in non-smokers for this cancer to develop is not clearly understood. Researchers analyzed the genomes of 138 lung adenocarcinoma patients, including smokers and non-smokers, with whole-genome sequencing technologies. They explored DNA damage that induced neoplastic transformation. Lung adenocarcinomas that originated from chronic smoking, referred to as signature 4-high (S4-high) cancers in the study, showed several distinguishing features compared to smoking-unrelated cancers (S4-low). People in the S4-high group were largely older, men and had more frequent mutations in a cancer-related gene called KRAS. Cancer genomes in the S4-high group were hypermutated with simple mutational classes, such as the substitution, insertion, or deletion of a single base, the building block of DNA. But the story was very different in the S4-low group. Generally, mutational profiles in this group were much more silent than the S4-high group. However, all cancer-related gene fusions, which are abnormally activated from the merging of two originally separate genes, were exclusively observed in the S4-low group. The patterns of genomic structural changes underlying gene fusions suggest that about three in four cases of gene fusions emerged from a single cellular crisis causing massive genomic fragmentation and subsequent imprecise repair in normal lung epithelium. Most strikingly, these major genomic rearrangements, which led to the development of lung adenocarcinoma, are very likely to be acquired decades before cancer diagnosis. The researchers used genomic archaeology techniques to trace the timing of when the catastrophes took place. Researchers started this study seven years ago when they discovered the expression of the KIF5B-RET gene fusion in lung adenocarcinoma for the first time. Professor Young-Seok Ju, co-lead author from the Graduate School of Medical Science and Engineering at KAIST says, “It is remarkable that oncogenesis can begin by a massive shattering of chromosomes early in life. Our study immediately raises a new question: What induces the mutational catastrophe in our normal lung epithelium.” Professor Young Tae Kim, co-lead author from Seoul National University says, “We hope this work will help us get one step closer to precision medicine for lung cancer patients.” The research team plans to further focus on the molecular mechanisms that stimulate complex rearrangements in the body, through screening the genomic structures of fusion genes in other cancer types. This study was supported by the National Research Foundation of Korea (NRF), Korea Health Industry Development Institute (KHIDI), Suh Kyungbae Foundation, the College of Medicine Research Foundations at Seoul National University and others. Figure. (Smoking-unrelated oncogenesis of lung cancers by gene fusions) Publication. Jake June-Koo Lee, Seongyeol Park et al., Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma Cell 177, June 13 2019, online publication ahead of print at May 30, 2019 https://doi.org/10.1016/j.cell.2019.05.013 Profile: Prof Young Seok Ju, MD, PhD email@example.com http://julab.kaist.ac.kr Associate Professor Graduate School of Medical Science and Engineering (GSMSE) Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141, Korea Profile: Prof Young Tae Kim, MD, PhD firstname.lastname@example.org Professor Seoul National University Cancer Research Institute Department of Thoracic and Cardiovascular Surgery Seoul National University Hospital Seoul 03080, Korea
5 Biomarkers for Overcoming Colorectal Cancer Drug Resistance Identified
< Professor Kwang-Hyun Cho's Team > KAIST researchers have identified five biomarkers that will help them address resistance to cancer-targeting therapeutics. This new treatment strategy will bring us one step closer to precision medicine for patients who showed resistance. Colorectal cancer is one of the most common types of cancer worldwide. The number of patients has surpassed 1 million, and its five-year survival rate significantly drops to about 20 percent when metastasized. In Korea, the surge of colorectal cancer has been the highest in the last 10 years due to increasing Westernized dietary patterns and obesity. It is expected that the number and mortality rates of colorectal cancer patients will increase sharply as the nation is rapidly facing an increase in its aging population. Recently, anticancer agents targeting only specific molecules of colon cancer cells have been developed. Unlike conventional anticancer medications, these selectively treat only specific target factors, so they can significantly reduce some of the side-effects of anticancer therapy while enhancing drug efficacy. Cetuximab is the most well-known FDA approved anticancer medication. It is a biomarker that predicts drug reactivity and utilizes the presence of the ‘KRAS’ gene mutation. Cetuximab is prescribed to patients who don’t carry the KRAS gene mutation. However, even in patients without the KRAS gene mutation, the response rate of Cetuximab is only about fifty percent, and there is also resistance to drugs after targeted chemotherapy. Compared with conventional chemotherapy alone, the life expectancy only lasts five months on average. In research featured in the FEBS Journal as the cover paper for the April 7 edition, the KAIST research team led by Professor Kwang-Hyun Cho at the Department of Bio and Brain Engineering presented five additional biomarkers that could increase Cetuximab responsiveness using systems biology approach that combines genomic data analysis, mathematical modeling, and cell experiments. The experimental inhibition of newly discovered biomarkers DUSP4, ETV5, GNB5, NT5E, and PHLDA1 in colorectal cancer cells has been shown to overcome Cetuximab resistance in KRAS-normal genes. The research team confirmed that when suppressing GNB5, one of the new biomarkers, it was shown to overcome resistance to Cetuximab regardless of having a mutation in the KRAS gene. Professor Cho said, “There has not been an example of colorectal cancer treatment involving regulation of the GNB5 gene.” He continued, “Identifying the principle of drug resistance in cancer cells through systems biology and discovering new biomarkers that could be a new molecular target to overcome drug resistance suggest real potential to actualize precision medicine.” This study was supported by the National Research Foundation of Korea (NRF) and funded by the Ministry of Science and ICT (2017R1A2A1A17069642 and 2015M3A9A7067220). Image 1. The cover of FEBS Journal for April 2019
KAIST Identifies the Cause of Sepsis-induced Lung Injury
(Professor Pilhan Kim from the Graduate School of Medical Science and Engineering) A KAIST research team succeeded in visualizing pulmonary microcirculation and circulating cells in vivo with a custom-built 3D intravital lung microscopic imaging system. They found a type of leukocyte called neutrophils aggregate inside the capillaries during sepsis-induced acute lung injury (ALI), leading to disturbances and dead space in blood microcirculation. According to the researchers, this phenomenon is responsible for tissue hypoxia causing lung damage in the sepsis model, and mitigating neutrophils improves microcirculation as well as hypoxia. The lungs are responsible for exchanging oxygen with carbon dioxide gases during the breathing process, providing an essential function for sustaining life. This gas exchange occurs in the alveoli, each surrounded by many capillaries containing the circulating red blood cells. Researchers have been making efforts to observe microcirculation in alveoli, but it has been technically challenging to capture high-resolution images of capillaries and red blood cells inside the lungs that are in constant breathing motion. Professor Pilhan Kim from the Graduate School of Medical Science and Engineering and his team developed an ultra-fast laser scanning confocal microscope and an imaging chamber that could minimize the movement of a lung while preserving its respiratory state. They used this technology to successfully capture red blood cell circulation inside the capillaries of animal models with sepsis. During the process, they found that hypoxia was induced by the increase of dead space inside the lungs of a sepsis model, a space where red blood cells do not circulate. This phenomenon is due to the neutrophils aggregating and trapping inside the capillaries and the arterioles. It was also shown that trapped neutrophils damage the lung tissue in the sepsis model by inhibiting microcirculation as well as releasing reactive oxygen species. Further studies showed that the aggregated neutrophils inside pulmonary vessels exhibit a higher expression of the Mac-1 receptor (CD11b/CD18), which is a receptor involved in intercellular adhesion, compared to the neutrophils that normally circulate. Additionally, they confirmed that Mac-1 inhibitors can improve inhibited microcirculation, ameliorate hypoxia, while reducing pulmonary edema in the sepsis model. Their high-resolution 3D intravital microscope technology allows the real-time imaging of living cells inside the lungs. This work is expected to be used in research on various lung diseases, including sepsis. The research team’s pulmonary circulation imaging and precise analytical techniques will be used as the base technology for developing new diagnostic technologies, evaluating new therapeutic agents for various diseases related to microcirculation. Professor Kim said, “In the ALI model, the inhibition of pulmonary microcirculation occurs due to neutrophils. By controlling this effect and improving microcirculation, it is possible to eliminate hypoxia and pulmonary edema – a new, effective strategy for treating patients with sepsis.” Their 3D intravital microscope technology was commercialized through IVIM Technology, Inc., which is a faculty startup at KAIST. They released an all-in-one intravital microscope model called ‘IVM-CM’ and ‘IVM-C’. This next-generation imaging equipment for basic biomedical research on the complex pathophysiology of various human diseases will play a crucial role in the future global bio-health market. This research, led by Dr. Inwon Park from the Department of Emergency Medicine at Seoul National University Bundang Hospital and formally the Graduate School of Medical Science and Engineering at KAIST, was published in the European Respiratory Journal (2019, 53:1800736) on March 28, 2019. Figure 1. Custom-built high-speed real-time intravital microscope platform Figure 2. Illustrative schematic and photo of a 3D intravital lung microscopic imaging system Figure 3. Aggregation of neutrophils and consequent flow disturbance in pulmonary arteriole in sepsis-induced lung injury
KAIST 2019 Commencement at a Glance
(KAIST 2019 Commencement Ceremony) This year, KAIST awarded a total of 2,705 degrees: 654 PhD degrees, 1,255 master’s degrees, and 796 bachelor’s degrees. Including this year’s numbers, KAIST has conferred a total of 63,830 degrees since its foundation in 1971. Parents, family, and friends came to campus to congratulate the graduates with big smiles and hugs. Faculty and staff members also attended the ceremony to celebrate their graduation. This year, distinguished guests including National Assembly Member Kyung-Jin Kim and Vice Minister for Science, Technology and Innovation Dae-sik came to celebrate the day with the KAIST community. During the commencement, KAIST also announced the recipients of its undergraduate academic awards. The Minister of Science and ICT Award was won by Do-Yoon Kim from the Department of Aerospace Engineering, the KAIST Board of Trustee Chairperson Award went to Se-rin Lee from the Department of Materials Science and Engineering, the KAIST Presidential Award was won by Hee-Ju Kim from the Department of Physics, the KAIST Alumni Association President Award went to Hyeon-Seong Park from the School of Electrical Engineering, and finally the KAIST Development Foundation Chairperson Award was won by Gyeong-Hoon Lee from the Department of Mathematical Sciences. This year’s valedictorian Eun-Seok Jeong from the School of Computing said, “I believe that we are able to stand here today because we challenged ourselves to confront our shortcomings and our uncertainty. If we continue to develop, we will become a better person than we were yesterday.” (KAIST President Sung-Chul Shin and Woo-Seok Jeong, '19 PhD in Aerospace Engineering) As a KAIST alumnus and fellow scientist, President Sung-Chul Shin offered his congratulations and emphasized that graduates should continue to pursue the C³ spirit. “In this age of great transformation, embrace challenges and exercise creativity as you have learnt through your education and research at KAIST. And keep in mind the importance of caring for others. Please remember that challenge and creativity will have more meaning if rendered with a caring spirit,” he said.
KAIST Earns AACSB Business School Accreditation
The KAIST College of Business re-earned business school accreditation from the Association to Advance Collegiate Schools of Business (AACSB) International. The school first earned the accreditation in 2003, and has continued to receive the accreditation four consecutive times. Currently only 5% of the 16,000 business schools around the world have earned AACSB accreditation. KAIST received a good evaluation for the competitive research of its faculty, its executive education programs based on strong industry-academia ties, and specialized MBA and master’s program, which includes programs such as social entrepreneurship and green business and policy.Alexander Triantis, dean of the Robert H. Smith School of Business at the University of Maryland and a judge for AACSB Accreditation said, “I was impressed to see students from KAIST have a high standard of knowledge. A number of its graduates continue to be appointed as professors of top universities abroad, which shows its strong global competence”. AACSB was founded in 1916 by deans of business colleges from prestigious universities such as Harvard University, Stanford University and Columbia University, to provide business and accounting accreditation to universities. Evaluation for AACSB accreditation takes place every five years. Schools are evaluated based on fifteen standards, including student admission and graduation requirements, student-faculty ratios, faculty’s intellectual contributions, research infrastructure, global cooperation, and industry-academia programs. They can be eligible for re-accreditation if they satisfy the conditions offered by AACSB International and are committed to continuous improvement every five years. KAIST also earned the accreditation from the European Foundation for Management Development Quality Improvement System (EQUIS) three consecutive times since 2010. In 2013, it earned membership into the Partnership in International Management (PIM). Membership is only possible for those who have AACSB and EQUIS accreditation and they can be listed as a candidate school through voting. The candidate schools can finally earn membership after one year of strict screening. As of January 2019, there are 65 prestigious graduate schools of business, including KAIST, listed as PIM members.
First Korean Member of OceanObs' Organizing Committee
Professor Sung Yong Kim from the Department of Mechanical Engineering became the first Korean to be elected as an organizing committee member of the international conference OceanObs’19’, specializing in the ocean observing field. Professor Kim has been actively engaged in advisory panels, technical committees, and working groups for the North Pacific Marine Science Organization (PICES). Through numerous activities, he was recognized for his professionalism and academic achievements, which led him to be appointed as a member of the organizing committee. The organizing committee is comprised of leading scholars and researchers from 20 countries, and Professor Kim will be the first Korean scientist to participate on the committee. Since 1999, the conference has been held every decade. Global experts specializing in oceanic observation gather to discuss research directions for the next ten years by monitoring physical, biological, and chemical variables in regional, national, and global oceans and applying marine engineering. This year, approximately 20 institutes including NASA’s Jet Propulsion Laboratory (JPL), the National Science Foundation, the National Oceanic and Atmospheric Administration, and the European Space Agency will support funds as well as high-tech equipment to the conference. This year’s conference theme is the governance of global ocean observing systems such as underwater gliders, unmanned vehicles, remote sensing, and observatories. The conference will hold discussions on monitoring technology and information systems to ensure human safety as well as to develop and preserve food resources. Additionally, participants will explore ways to expand observational infrastructures and carry out multidisciplinary approaches. There will also be collaborations with the Global Ocean Observing System (GOOS) and the Partnership for Observation of the Global Oceans (POGO) to organize ocean observing programs and discuss priorities. Finally, they will set a long-term plan for solving major scientific issues, such as climate change, ocean acidification, energy, and marine pollution. Professor Kim said, “Based on the outcomes drawn from the conference, I will carry out research on natural disasters and climate change monitoring by using unmanned observing systems. I will also encourage more multidisciplinary research in this field.”
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.”
The 1st Korea Toray Science and Technology Awardee, Prof. Sukbok Chang
(Distinguished Professor Sukbok Chang from the Department of Chemistry) The Korea Toray Science Foundation (KTSF) awarded the first Korea Toray Science Technology Award in basic science to Distinguished Professor Sukbok Chang from the Department of Chemistry on September 19. KTSF was established in January 2018, and its award goes to researchers who have significantly contributed to the development of chemistry and materials research with funds to support research projects. Distinguished Professor Chang has devoted himself in organocatalysis research; in particular, his work on catalysts for effective lactam formation, which was an intricate problem, received great attention. The award ceremony will take place in The Federation of Korean Industries Hall on October 31. KTFS board members, judges, and the CEO of Toray Industries Akihiro Nikkaku will attend the ceremony. Also, Dr. Ryoji Noyori, the Nobel Laureate in Chemistry, will give a talk on the role of chemistry and creative challenges as a researcher.
Center for Industrial Future Strategy Takes Off at KAIST
Professor Suh Chosen for IT Young Engineer Award
(The ceremony photo of Professor Changho Suh) Professor Changho Suh from the School of Electrical Engineering received the IT Young Engineer Award on June 28. This award is hosted by the Institute of Electrical and Electronics Engineers (IEEE) and the Institute of Electrical and Information Engineers (IEIE) and funded by the Haedong Science Foundation. The IT Young Engineer Award is given to researchers under the age of 40 in Korea. The selection criteria include the researches’ technical practicability, their social and environmental contributions, and their creativity. Professor Suh has shown outstanding academic performance in the field of telecommunications, distributed storage, and artificial intelligence and he has also contributed to technological commercialization. He published 23 papers in SCI journals and ten papers at top-level international conferences including the Conference on Neural Information Processing Systems and the International Conference on Machine Learning. His papers were cited more than 4,100 times. He has also achieved 30 international patent registrations. Currently, he is developing an autonomous driving system using an AI-tutor and deep learning technology. Professor Suh said, “It is my great honor to receive the IT Young Engineer Award. I strive to continue guiding students and carrying out research in order to make a contribution to the fields of IT and AI.”
ICT Volunteer Corps Off to Africa
A volunteer corps made up of students will take part in ICT education services in Ethiopia, Tanzania, and Uganda. KAIST students have been volunteering with the ICT education program in Africa since 2015. The volunteer corps will be made up of 51 students from 13 teams and will be conducting services for a month through the end of July at Addis Ababa Institute of Technology (AAiT) in Ethiopia, Nelson Mandela African Institute of Science and Technology (NM-AIST) and Star High School in Tanzania, and IT Education Center in Uganda. In Tanzania, KAIST students teamed up with NM-AIST students to carry out appropriate technology programs applied with Arduino kits. They plan to use scientific and engineering approaches to address local residents’ living challenges such as developing agricultural water suppliers using sensors measuring water in the soil and oxygen suppliers in the reservoir. Meanwhile, in Ethiopia and Uganda, student volunteers will be involved in various ICT educational programs for local students. The volunteering corps will also introduce cultural programs including K-Pop dancing for young students there. They will also engage in sports and art classes for students at orphanages in the region. President Sung-Chul Shin encouraged volunteers at the kick-off ceremony saying, “KAIST students should keep always humility, warmth, and tolerance in mind. I believe our students will exert leadership out there along with knowledge as well as wisdom.”
Taming AI: Engineering, Ethics, and Policy
(Professor Lee, Professor Koene, Professor Walsh, and Professor Ema (from left)) Can AI-powered robotics could be adequate companions for humans? Will the good faith of users and developers work for helping AI-powered robots become the new tribe of the digital future? AI’s efficiency is creating new socio-economic opportunities in the global market. Despite the opportunities, challenges still remain. It is said that efficiency-enforcing algorithms through deep learning will take an eventual toll on human dignity and safety, bringing out the disastrous fiascos featured in the Terminator movies. A research group at the Korean Flagship AI Project for Emotional Digital Companionship at KAIST Institute for AI (KI4AI) and the Fourth Industrial Intelligence Center at KAIST Institute co-hosted a seminar, “Taming AI: Engineering, Ethics, and Policy” last week to discuss ways to better employ AI technologies in ways that upholds human values. The KI4AI has been conducting this flagship project from the end of 2016 with the support of the Ministry of Science and ICT. The seminar brought together three speakers from Australia, Japan, and the UK to better fathom the implications of the new technology emergence from the ethical perspectives of engineering and discuss policymaking for the responsible usage of technology. Professor Toby Walsh, an anti-autonomous weapon activist from New South Wales University in Australia continued to argue the possible risk that AI poses to malfunction. He said that an independent ethics committee or group usually monitors academic institutions’ research activities in order to avoid any possible mishaps. However, he said there is no independent group or committee monitoring the nature of corporations’ engagement of such technologies, while its possible threats against humanity are alleged to be growing. He mentioned that Google’s and Amazon’s information collecting also pose a potent threat. He said that ethical standards similar to academic research integrity should be established to avoid the possible restricting of the dignity of humans and mass destruction. He hoped that KAIST and Google would play a leading role in establishing an international norm toward this compelling issue. Professor Arisa Ema from the University of Tokyo provided very compelling arguments for thinking about the duplicity of technology and how technology should serve the public interest without any bias against gender, race, and social stratum. She pointed out the information dominated by several Western corporations like Google. She said that such algorithms for deep learning of data provided by several Western corporations will create very biased information, only applicable to limited races and classes. Meanwhile, Professor Ansgar Koene from the University of Nottingham presented the IEEE’s global initiative on the ethics of autonomous and intelligence systems. He shared the cases of industry standards and ethically-aligned designs made by the IEEE Standards Association. He said more than 250 global cross-disciplinary thought leaders from around the world joined to develop ethical guidelines called Ethically Aligned Design (EAD) V2. EAD V2 includes methodologies to guide ethical research and design, embedding values into autonomous intelligence systems among others. For the next step beyond EAD V2, the association is now working for IEEE P70xx Standards Projects, detailing more technical approaches. Professor Soo Young Lee at KAIST argued that the eventual goal of complete AI is to have human-like emotions, calling it a new paradigm for the relationship between humans and AI-robots. According to Professor Lee, AI-powered robots will serve as a good companion for humans. “Especially in aging societies affecting the globe, this will be a very viable and practical option,” he said. He pointed out, “Kids learn from parents’ morality and social behavior. Users should have AI-robots learn morality as well. Their relationships should be based on good faith and trust, no longer that of master and slave. He said that liability issues for any mishap will need to be discussed further, but basically each user and developer should have their own responsibility when dealing with these issues.
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