IR
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MCM Utilized at Residential Treatment Center in Gyeonggi
The Mobile Clinic Module (MCM) developed by the KAIST Action for Respiratory Epidemics was installed at special residential treatment center in Gyeonggi Province on September 13.
The MCM is an isolate negative pressure unit fitted with high-quality medical equipment, developed by Professor Taek-Jin Nam of the Department of Industrial Design under the KAIST New Deal R&D Initiative. This is also a part of the Korean Disease Control Package Development Project from last July.
In January, a ward with four beds for critical care was installed at the Korea Institute for Radiological & Medical Sciences in Seoul for a trial operation, and two mild cases were treated there. It was also implemented as an isolated negative pressure unit in the Daejeon Konyang University Hospital emergency room in June, and has treated 138 cases since.
The special residential treatment center installed in the Gyeonggi Provincial Academy gymnasium, which consists of 28 beds in 14 rooms (double occupancy) and a multipurpose room (for X-rays and treatment), is to remain open through October 10. Unlike existing treatment centers that have quarantined COVID-19 patients for two weeks, the Gyeonggi MCM will act as a self-treatment-associated short-term treatment center. While in self-treatment, patients showing symptoms requiring special attention will be moved to the MCM, followed by short-term hospitalization of 1-3 days for observation before further measures are taken.
Patients can be treated using the MCM’s own treatment capacities, including in-person and oxygen treatment, X-rays, and IVs. There are individual bathrooms in each room, and the pressure, ventilation, and the automatic opening and closing of the entrance can be centrally monitored and controlled. Patients showing symptoms during treatment will be moved to a specially designated hospital for critical care, and will return to the self-treatment center if no further abnormalities are reported.
The Gyeonggi Provincial Medical Center’s Ansung Hospital will take charge of operating the special treatment center. Each day, one or two doctors, three nurses, two nursing assistants, one administrative staff member, two or three disinfection specialists, and a medical imaging engineer will work in three shifts. There will also be about 20 additional specially designated staff members including KAIST researchers, firefighters, and police officers.
The MCM was internationally recognized as an excellent medical facility not only for its functionality, economic feasibility, and utility, but also for its unique design and aesthetics. It received two Best of Best awards at the Red Dot Award in product design and Communication Design in user interface.
By running this special treatment center, KAIST will conduct research on how to build an optimized model for efficient negative pressure medical units. This research is expected to lead to advances in waste water treatment systems, mobile bathrooms optimized for infectious cases, and MCM user interfaces for electronic devices, etc.
Professor Taek-Jin Nam, the general director of the project and design, said “if there is a gymnasium available, we can convert it into a special treatment center fitted with a waste water treatment system, and pressure equipment in two weeks even without additional infrastructure.”
The head of the KAIST New Deal R&D Initiative Choongsik Bae said, “our MCM research started in July of last year, and in just over a year, it has become a successful and innovative case that has undergone trials and become commercialized in a short period of time.” He added, “In response to COVID-19, KAIST is conducting research and empirical studies, not just in relation to the MCM, but in other areas of disease control as well.”
Based on the excellent disease control technologies developed by KAIST research teams, the KAIST Action for Respiratory Epidemics is conducting technology transfers and industrialization, and is developing a Korean disease control package model
2021.09.15 View 7424 -
Aline and Blow-yancy Win the Red Dot Design Awards: Brand & Communications Design 2021
‘Aline’ and ‘Blow-yancy’ developed by Professor Sang Su Lee’s team at the Department of Industrial Design won the Red Dot Design Awards in Brand & Communications Design. Aline is a mobile investment portfolio application used in the NH Investment & Securities Co. Blow-yancy is a suva diving VR device for neutral buoyancy training.Professor Lee sought ‘sustainability’ while developing Aline to meet the growing awareness of ESG (environmental, social, and governance) investing. ESG investing relies on independent ratings that help consumers assess a company’s behavior and policies when it comes to its social impact.
Aline’s personal value index with six main criteria translates values into sustainable finance. By gathering data from the initial survey and regular value updates, the index is weighted according to the user’s values. Based on the index, the investment portfolio will be adjusted, and consumption against the values will be tracked.
Blow-yancy is a diving VR device for neutral buoyancy training. Blow-yancy’s VR mask helps divers feel like they are wearing an actual diving mask. Users can breathe through a regulator with a built-in breathing sensor. It allows training like actual diving without going into the water, therefore enabling safer diving.
“We got an idea that about 74% of scuba divers come into contact with corals underwater at least once and that can cause an emergency situation. Divers who cannot maintain neutral buoyance will experience a tough time avoiding them,” said Professor Lee.
The hardware consists of a nose covering VR mask, a regulator with a built-in breath sensor, and a controller for virtual BCD control. Blow-yancy’s five virtual missions were organized according to the diving process required by PADI, a professional diving education institute.
Professor Lee’s team already received eight recognitions at the iF Design Award in April. Professor Lee said, “We will continue to develop the best UX design items that will improve our global recognition.”
2021.08.26 View 4105 -
KAIST KPC4IR Presents the AI Global Guide for Healthcare
The benchmark for the responsible usage of AI technology in the healthcare sector will promote clarity and high standards for technological applications
The KAIST Korea Policy Center for the Fourth Industrial Revolution (KPC4IR) published 'Using AI to Support Healthcare Decisions: A Guide for Society.' This global guide is designed to serve as a benchmark for the responsible usage of AI technologies, and will promote clarity and high standards for technological applications in the healthcare sector. The guide details what should be considered when making clinical decisions to help reduce the chances of the AI giving false or misleading results.
The KPC4IR presented the guide in collaboration with the Lloyd’s Register Foundation Institute for the Public Understanding of Risk at the National University of Singapore (NUS IPUR) and Sense about Science, a non-profit organization in the UK specialized in science communication, during the 2021 SIG-KDD (Special Interest Group on Knowledge Discovery and Data Mining) Conference on August 15.
AI technology is being widely used in the healthcare sector and has already proved its accuracy and efficiency in diagnosing and predicting diseases. Despite its huge impact on our daily lives in every sector of society, AI technology has some drawbacks and comes with risks, especially due to biased algorithms.
“We focused on the ‘reliability’ of AI applications in the healthcare sector to make all data well represented, in good quality. The technology will eventually innovate to better serve the people’s new demand, especially critical demands for safety and precision in healthcare services. This global guide will help both developers and people’s understanding of the appropriate technology applications,” says Director So Young Kim at the KPC4IR.
The guide, for instance, says that to scrutinize quality and reliability, the source of the data must be clearly known; the data must have been collected or selected for the purpose it’s being used for; the limitations and assumptions for that purpose have been clearly stated; the biases have been addressed; and it has been properly tested in the real world. It also reflects the importance of the representativeness of data that will affect the accuracy of the AI applications.
“By being transparent and demonstrating the steps taken to check that the AI is reliable, researchers and developers can help give people confidence about providing their data,” the guide states.
For this guide, the KPC4IR and its collaborators collected data after working with numerous experts from the Graduate School of AI at KAIST, the Science and Technology Policy Institute in Korea, Asan Medical Center in Seoul, Seoul National University Bundang Hospital, and AI solution companies.
2021.08.17 View 5460 -
A Study Reveals What Triggers Lung Damage during COVID-19
A longitudinal study of macrophages from SARS-CoV-2 infected lungs offers new insights into dynamic immunological changes
A KAIST immunology research team found that a specific subtype of macrophages that originated from blood monocytes plays a key role in the hyper-inflammatory response in SARS-CoV-2 infected lungs, by performing single-cell RNA sequencing of bronchoalveolar lavage fluid cells. This study provides new insights for understanding dynamic changes in immune responses to COVID-19.
In the early phase of COVID-19, SARS-CoV-2 infected lung tissue and the immediate defense system is activated. This early and fast response is called ‘innate immunity,’ provided by immune cells residing in lungs. Macrophages are major cell types of the innate immune system of the lungs, and newly differentiated macrophages originating from the bloodstream also contribute to early defenses against viruses.
Professor Su-Hyung Park and his collaborators investigated the quantitative and qualitative evaluation of immune responses in the lungs of SARS-CoV-2 infected ferrets. To overcome the limitations of research using patient-originated specimens, the researchers used a ferret infection model to obtain SARS-CoV-2 infected lungs sequentially with a defined time interval.
The researchers analyzed the 10 subtypes of macrophages during the five-day course of SARS-CoV-2 infection, and found that infiltrating macrophages originating from activated monocytes in the blood were key players for viral clearance as well as damaged lung tissue. Moreover, they found that the differentiation process of these inflammatory macrophages resembled the immune responses in the lung tissue of severe COVID-19 patients.
Currently, the research team is conducting a follow-up study to identify the dynamic changes in immune responses during the use of immunosuppressive agents to control hyper-inflammatory response called ‘cytokine storm’ in patients with COVID-19.
Dr. Jeong Seok Lee, the chief medical officer at Genome Insight Inc., explained, “Our analysis will enhance the understanding of the early features of COVID-19 immunity and provide a scientific background for the more precise use of immunosuppressive agents targeting specific macrophage subtypes.”
“This study is the first longitudinal study using sequentially obtained immune cells originating from SARS-CoV-2 infected lungs. The research describes the innate immune response to COVID-19 using single cell transcriptome data and enhances our understanding of the two phases of inflammatory responses,” Professor Park said.
This work was supported by the Ministry of Health and Welfare and KAIST, and was published in Nature Communications on July 28.
-PublicationSu-Hyung Park, Jeong Seok Lee, Su-Hyung Park et al. “Single-cell transcriptome of bronchoalverolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets” Nature Communications (https://doi.org/10.1038/s41467-021-24807-0)
-ProfileProfessor Su-Hyung ParkLaboratory of Translational Immunology and Vaccinologyhttps://ltiv.kaist.ac.kr/
Graduate School of Medical Science and EngineeringKAIST
2021.08.04 View 9566 -
KPC4IR Helping to Create Global Standards for Virtual Transactions
KPC4IR will join the task force for the Global Implementation of Travel Rule Standards
The KAIST Policy Center for the Fourth Industrial Revolution (KPC4IR) will participate in a global initiative to create global standards for virtual asset transactions. As a member of the GI-TRUST (Global Implementation of Travel Rule Standards) task force, the KPC4IR will develop technical standards and relevant policies that support the global implementation of the travel rule for virtual assets in compliance with the recommendations of the Financial Action Task Force’s (FATF).
The FATF is an intergovernmental organization founded in 1989 by the G7 to develop policies to combat money laundering. In June 2019, the FATF extended its Recommendation 16, commonly known as the “travel rule,” to virtual asset services providers (VASPs), requiring both financial institutions and VASPs to aggregate information on the senders and recipients of wire transfers and exchange this information between parties to create a suitable audit trail.
According to the FATF’s recommendation and the G20’s support, jurisdictions, especially G20 member countries, have now applied the travel rule to their respective local laws. Korea also amended the Act on Reporting and Using Specified Financial Transaction Information in March 2020 to include virtual assets in their regulatory scope by March 2022.
The GI-TRUST task force will collaborate with global and local organizations developing travel rule technologies and offer a neutral assessment of proposed solutions. Their activities are aimed at standardizing related authentication protocols and security technologies that help VASPs comply with the travel rule.
The task force will also aid in the pilot testing of travel rule solutions for certain VASPs in Korea. Afterwards, the task force will report on the performance and reliability of the tested travel rule solutions for actual virtual asset transactions, in compliance with the FATF’s guidance.
Besides the KPC4IR, the GI-TRUST task force includes the Global Blockchain Business Council (GBBC), International Digital Asset Exchange Association (IDAXA), and Korea Blockchain Association (KBCA).
Director of the KPC4IR Professor So Young Kim will co-chair the task force. Professor Kim said their approach should be prudential in dealing with the regulations that rely on secure real-name data on top of the opposing governance style of pseudonymization, distribution, and recombination.
She explained, “KAIST has designed the co-evolution of technologies and institutions in conjunction with the global leaders’ groups such as the World Economic Forum and the EC Joint Research Center.”
She expects KAIST’s interdisciplinary, global cooperation to untie the entangled problem between regulations and technologies that obstruct future pathways.
2021.07.30 View 5973 -
Repurposed Drugs Present New Strategy for Treating COVID-19
Virtual screening of 6,218 drugs and cell-based assays identifies best therapeutic medication candidates
A joint research group from KAIST and Institut Pasteur Korea has identified repurposed drugs for COVID-19 treatment through virtual screening and cell-based assays. The research team suggested the strategy for virtual screening with greatly reduced false positives by incorporating pre-docking filtering based on shape similarity and post-docking filtering based on interaction similarity. This strategy will help develop therapeutic medications for COVID-19 and other antiviral diseases more rapidly. This study was reported at the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
Researchers screened 6,218 drugs from a collection of FDA-approved drugs or those under clinical trial and identified 38 potential repurposed drugs for COVID-19 with this strategy. Among them, seven compounds inhibited SARS-CoV-2 replication in Vero cells. Three of these drugs, emodin, omipalisib, and tipifarnib, showed anti-SARS-CoV-2 activity in human lung cells, Calu-3.
Drug repurposing is a practical strategy for developing antiviral drugs in a short period of time, especially during a global pandemic. In many instances, drug repurposing starts with the virtual screening of approved drugs. However, the actual hit rate of virtual screening is low and most of the predicted drug candidates are false positives.
The research group developed effective filtering algorithms before and after the docking simulations to improve the hit rates. In the pre-docking filtering process, compounds with similar shapes to the known active compounds for each target protein were selected and used for docking simulations. In the post-docking filtering process, the chemicals identified through their docking simulations were evaluated considering the docking energy and the similarity of the protein-ligand interactions with the known active compounds.
The experimental results showed that the virtual screening strategy reached a high hit rate of 18.4%, leading to the identification of seven potential drugs out of the 38 drugs initially selected.
“We plan to conduct further preclinical trials for optimizing drug concentrations as one of the three candidates didn’t resolve the toxicity issues in preclinical trials,” said Woo Dae Jang, one of the researchers from KAIST.
“The most important part of this research is that we developed a platform technology that can rapidly identify novel compounds for COVID-19 treatment. If we use this technology, we will be able to quickly respond to new infectious diseases as well as variants of the coronavirus,” said Distinguished Professor Sang Yup Lee.
This work was supported by the KAIST Mobile Clinic Module Project funded by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF). The National Culture Collection for Pathogens in Korea provided the SARS-CoV-2 (NCCP43326).
-PublicationWoo Dae Jang, Sangeun Jeon, Seungtaek Kim, and Sang Yup Lee. Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay. Proc. Natl. Acad. Sci. U.S.A. (https://doi/org/10.1073/pnas.2024302118)
-ProfileDistinguished Professor Sang Yup LeeMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.kr
Department of Chemical and Biomolecular EngineeringKAIST
2021.07.08 View 9004 -
Study of T Cells from COVID-19 Convalescents Guides Vaccine Strategies
Researchers confirm that most COVID-19 patients in their convalescent stage carry stem cell-like memory T cells for months
A KAIST immunology research team found that most convalescent patients of COVID-19 develop and maintain T cell memory for over 10 months regardless of the severity of their symptoms. In addition, memory T cells proliferate rapidly after encountering their cognate antigen and accomplish their multifunctional roles. This study provides new insights for effective vaccine strategies against COVID-19, considering the self-renewal capacity and multipotency of memory T cells.
COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. When patients recover from COVID-19, SARS-CoV-2-specific adaptive immune memory is developed. The adaptive immune system consists of two principal components: B cells that produce antibodies and T cells that eliminate infected cells. The current results suggest that the protective immune function of memory T cells will be implemented upon re-exposure to SARS-CoV-2.
Recently, the role of memory T cells against SARS-CoV-2 has been gaining attention as neutralizing antibodies wane after recovery. Although memory T cells cannot prevent the infection itself, they play a central role in preventing the severe progression of COVID-19. However, the longevity and functional maintenance of SARS-CoV-2-specific memory T cells remain unknown.
Professor Eui-Cheol Shin and his collaborators investigated the characteristics and functions of stem cell-like memory T cells, which are expected to play a crucial role in long-term immunity. Researchers analyzed the generation of stem cell-like memory T cells and multi-cytokine producing polyfunctional memory T cells, using cutting-edge immunological techniques.
This research is significant in that revealing the long-term immunity of COVID-19 convalescent patients provides an indicator regarding the long-term persistence of T cell immunity, one of the main goals of future vaccine development, as well as evaluating the long-term efficacy of currently available COVID-19 vaccines.
The research team is presently conducting a follow-up study to identify the memory T cell formation and functional characteristics of those who received COVID-19 vaccines, and to understand the immunological effect of COVID-19 vaccines by comparing the characteristics of memory T cells from vaccinated individuals with those of COVID-19 convalescent patients.
PhD candidate Jae Hyung Jung and Dr. Min-Seok Rha, a clinical fellow at Yonsei Severance Hospital, who led the study together explained, “Our analysis will enhance the understanding of COVID-19 immunity and establish an index for COVID-19 vaccine-induced memory T cells.”
“This study is the world’s longest longitudinal study on differentiation and functions of memory T cells among COVID-19 convalescent patients. The research on the temporal dynamics of immune responses has laid the groundwork for building a strategy for next-generation vaccine development,” Professor Shin added. This work was supported by the Samsung Science and Technology Foundation and KAIST, and was published in Nature Communications on June 30.
-Publication:
Jung, J.H., Rha, MS., Sa, M. et al. SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells. Nat Communications 12, 4043 (2021). https://doi.org/10.1038/s41467-021-24377-1
-Profile:
Professor Eui-Cheol Shin
Laboratory of Immunology & Infectious Diseases (http://liid.kaist.ac.kr/)
Graduate School of Medical Science and Engineering
KAIST
2021.07.05 View 8875 -
KAIST-SM Entertainment Joint Research for Metaverse
“Culture scientist will play a role in the future of the entertainment industry”
KAIST President Kwang Hyung Lee and SM Entertainment Founder and Chief Executive Producer Soo-Man Lee signed an MOU on joint research of the metaverse on June 23 at the Daejeon campus. SM Entertainment is the powerhouse of K-pop and Lee is a pioneering figure who helped Korean pop culture emerge into a global phenomenon.
The KAIST-SM metaverse partnership will bring out new culture technology that will lead the virtual entertainment industry by creating more dynamic and vivid digital technologies. KAIST will utilize its AI, robot, and network technologies, while SM will provide its content production expertise for this metaverse research.
President Lee said, “SM artists have mesmerized global audiences and opened new markets for K-Pop. Combining the creativity and cultural imagination of SM with technologies from KAIST, together we will make significant contributions to the advancement of virtual reality as well as the global entertainment industry.”
The Graduate School of Culture Technology has been engaging in a variety of creative projects incorporating science and technology for decades and will now actively participate in this metaverse project with SM.
CEP Lee explained, “The power of celebrities and avatars will rule the future entertainment industry. SM will make a leap forward to be a ‘first mover’ in the digital entertainment industry with this partnership with KAIST. This partnership will shape the new digital future of the entertainment industry boosted by cutting-edge technologies.”
CEP Lee also delivered a special lecture for the KAIST community via Zoom. Saying that producers in the future will be ‘culture scientists’, he stressed the importance of technology converging with culture.
“The key factor for K-pop’s success lies in the impressive technology of Korea. SM places a high priority on developing cultural technology and creating new artists and products combining this technology,” added Lee, citing the hologram contents of Beyond Live concerts and the new 4+4 girl group composed of four girls and four avatars called ‘Aespa.’
2021.06.25 View 4923 -
Ultrafast, on-Chip PCR Could Speed Up Diagnoses during Pandemics
A rapid point-of-care diagnostic plasmofluidic chip can deliver result in only 8 minutes
Reverse transcription-polymerase chain reaction (RT-PCR) has been the gold standard for diagnosis during the COVID-19 pandemic. However, the PCR portion of the test requires bulky, expensive machines and takes about an hour to complete, making it difficult to quickly diagnose someone at a testing site. Now, researchers at KAIST have developed a plasmofluidic chip that can perform PCR in only about 8 minutes, which could speed up diagnoses during current and future pandemics.
The rapid diagnosis of COVID-19 and other highly contagious viral diseases is important for timely medical care, quarantining and contact tracing. Currently, RT-PCR uses enzymes to reverse transcribe tiny amounts of viral RNA to DNA, and then amplifies the DNA so that it can be detected by a fluorescent probe. It is the most sensitive and reliable diagnostic method.
But because the PCR portion of the test requires 30-40 cycles of heating and cooling in special machines, it takes about an hour to perform, and samples must typically be sent away to a lab, meaning that a patient usually has to wait a day or two to receive their diagnosis.
Professor Ki-Hun Jeong at the Department of Bio and Brain Engineering and his colleagues wanted to develop a plasmofluidic PCR chip that could quickly heat and cool miniscule volumes of liquids, allowing accurate point-of-care diagnoses in a fraction of the time. The research was reported in ACS Nano on May 19.
The researchers devised a postage stamp-sized polydimethylsiloxane chip with a microchamber array for the PCR reactions. When a drop of a sample is added to the chip, a vacuum pulls the liquid into the microchambers, which are positioned above glass nanopillars with gold nanoislands. Any microbubbles, which could interfere with the PCR reaction, diffuse out through an air-permeable wall. When a white LED is turned on beneath the chip, the gold nanoislands on the nanopillars quickly convert light to heat, and then rapidly cool when the light is switched off.
The researchers tested the device on a piece of DNA containing a SARS-CoV-2 gene, accomplishing 40 heating and cooling cycles and fluorescence detection in only 5 minutes, with an additional 3 minutes for sample loading. The amplification efficiency was 91%, whereas a comparable conventional PCR process has an efficiency of 98%. With the reverse transcriptase step added prior to sample loading, the entire testing time with the new method could take 10-13 minutes, as opposed to about an hour for typical RT-PCR testing. The new device could provide many opportunities for rapid point-of-care diagnostics during a pandemic, the researchers say.
-Publication
Ultrafast and Real-Time Nanoplasmonic On-Chip Polymerase Chain Reaction for Rapid and Quantitative Molecular Diagnostics
ACS Nano (https://doi.org/10.1021/acsnano.1c02154)
-Professor
Ki-Hun Jeong
Biophotonics Laboratory
https://biophotonics.kaist.ac.kr/
Department of Bio and Brain Engineeinrg
KAIST
2021.06.08 View 7099 -
KAIST to join Deep Space Exploration Project
KAIST agreed to launch the Deep Space Exploration Research Consortium with two key leading aerospace research institutes, the Korea Aerospace Research Institute (KARI) and the Korea Astronomy and Space Science Institute (KASI) during a recent meeting at the KAIST campus. President Kwang Hyung Lee, KARI President Sang-Yool Lee, KASI President Young-Deuk Park, and Vice Minister of Science and ICT Hong-taek Yong attended the meeting to discuss medium- and long-term deep space exploration plans and collaborations.
The three entities have cooperated in scientific research for the last 30 years during which Korea has been developing its space exploration expertise. They signed the MoU for Cooperation for R&D and Industrialization on Deep Space Exploration’ last December. The research consortium will share and discuss research plans for space science research and exploration technology, and contribute to planning the nation’s deep space exploration.
At the meeting, KAIST reported its plans to return KITSAT-1 to Earth, Korea’s first satellite using local technology, and to explore the radiation belt (the Van Allen belt) around Earth. KAIST launched Korea’s first satellite KITSAT-1 in 1992. Meanwhile, KARI shared their plans to launch a lunar landing module using a Korean Space Launch Vehicle by 2030 and explained the current technologies and research related to a lunar landing and space exploration. Based on the payload technology it has been building on for the last 20 years, KASI emphasized the importance of research for deep space exploration in relation to the formation of the universe and the origin of mankind.
Vice Minister of Science and Technology Yong also stressed that “to enhance Korea’s capabilities for space research after launching our space launch vehicle, Nuri, in October, there must be continued efforts and preparation for higher level space research, including space exploration planning. The various experts’ opinions discussed in today’s meeting will be taken into consideration for governmental policies related to the ‘National Space Exploration Roadmap’ to be established in the latter half of this year.”
2021.06.07 View 5519 -
Identification of How Chemotherapy Drug Works Could Deliver Personalized Cancer Treatment
The chemotherapy drug decitabine is commonly used to treat patients with blood cancers, but its response rate is somewhat low. Researchers have now identified why this is the case, opening the door to more personalized cancer therapies for those with these types of cancers, and perhaps further afield.
Researchers have identified the genetic and molecular mechanisms within cells that make the chemotherapy drug decitabine—used to treat patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) —work for some patients but not others. The findings should assist clinicians in developing more patient-specific treatment strategies.
The findings were published in the Proceedings of the National Academies of Science on March 30.
The chemotherapy drug decitabine, also known by its brand name Dacogen, works by modifying our DNA that in turn switches on genes that stop the cancer cells from growing and replicating. However, decitabine’s response rate is somewhat low (showing improvement in just 30-35% of patients), which leaves something of a mystery as to why it works well for some patients but not for others. To find out why this happens, researchers from the KAIST investigated the molecular mediators that are involved with regulating the effects of the drug.
Decitabine works to activate the production of endogenous retroviruses (ERVs), which in turn induces an immune response. ERVs are viruses that long ago inserted dormant copies of themselves into the human genome. Decitabine in essence, ‘reactivates’ these viral elements and produces double-stranded RNAs (dsRNAs) that the immune system views as a foreign body.
“However, the mechanisms involved in this process, in particular how production and transport of these ERV dsRNAs were regulated within the cell were understudied,” said corresponding author Yoosik Kim, professor in the Department of Chemical and Biomolecular Engineering at KAIST.
“So to explain why decitabine works in some patients but not others, we investigated what these molecular mechanisms were,” added Kim.
To do so, the researchers used image-based RNA interference (RNAi) screening. This is a relatively new technique in which specific sequences within a genome are knocked out of action or “downregulated.” Large-scale screening, which can be performed in cultured cells or within live organisms, works to investigate the function of different genes. The KAIST researchers collaborated with the Institut Pasteur Korea to analyze the effect of downregulating genes that recognize ERV dsRNAs and could be involved in the cellular response to decitabine.
From these initial screening results, they performed an even more detailed downregulation screening analysis. Through the screening, they were able to identify two particular gene sequences involved in the production of an RNA-binding protein called Staufen1 and the production of a strand of RNA that does not in turn produce any proteins called TINCR that play a key regulatory role in response to the drug. Staufen1 binds directly to dsRNAs and stabilizes them in concert with the TINCR.
If a patient is not producing sufficient Staufen1 and TINCR, then the dsRNA viral mimics quickly degrade before the immune system can spot them. And, crucially for cancer therapy, this means that patients with lower expression (activation) of these sequences will show inferior response to decitabine. Indeed, the researchers confirmed that MDS/AML patients with low Staufen1 and TINCR expression did not benefit from decitabine therapy.
“We can now isolate patients who will not benefit from the therapy and direct them to a different type of therapy,” said first author Yongsuk Ku. “This serves as an important step toward developing a patient-specific treatment cancer strategy.”
As the researchers used patient samples taken from bone marrow, the next step will be to try to develop a testing method that can identify the problem from just blood samples, which are much easier to acquire from patients.
The team plans to investigate if the analysis can be extended to patients with solid tumors in addition to those with blood cancers.
-Profile
Professor Yoosik Kim
https://qcbio.kaist.ac.kr/
Department of Chemical and Biomolecular Engineering
KAIST
-Publication
Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs, PNAS
2021.05.24 View 7057 -
Mobile Clinic Module Wins Red Dot and iF Design Awards
The Mobile Clinic Module (MCM), an inflatable negative pressure ward building system developed by the Korea Aid for Respiratory Epidemic (KARE) initiative at KAIST, gained international acclaim by winning the prestigious Red Dot Design Award and iF Design Award.
The MCM was recognized as one of the Red Dot Product Designs of the Year. It also won four iF Design Awards in communication design, interior architecture, user interface, and user experience. Winning the two most influential design awards demonstrates how product design can make a valuable contribution to help contain pandemics and reflects new consumer trends for dealing with pandemics.
Designed to be patient friendly, even in the extreme medical situations such as pandemics or triage, the MCM is the result of collaborations among researchers in a variety of fields including mechanical engineering, computing, industrial and systems engineering, medical hospitals, and engineering companies. The research team was led by Professor Tek-Jin Nam from the Department of Industrial Design.
The MCM is expandable, moveable, and easy to store through a combination of negative pressure frames, air tents, and multi-functional panels. Positive air pressure devices supply fresh air from outside the tent. An air pump and controller maintain air beam pressure, while filtering exhausted air from inside. An internal air information monitoring system efficiently controls inside air pressure and purifies the air. It requires only one-fourth of the volume of existing wards and takes up approximately 40% of their weight. The unit can be transported in a 40-foot container truck.
MCMs are now located at the Korea Institute of Radiological & Medical Sciences and Jeju Vaccine Center and expect to be used at many other facilities. KARE is developing antiviral solutions and devices such as protective gear, sterilizers, and test kits to promptly respond to the pandemic. More than 100 researchers at KAIST are collaborating with industry and clinical hospitals to develop antiviral technologies that will improve preventive measures, diagnoses, and treatments.
Professor Nam said, “Our designers will continue to identify the most challenging issues, and try to resolve them by realizing user-friendly functions. We believe this will significantly contribute to relieving the drastic need for negative pressure beds and provide a place for monitoring patients with moderate symptoms. We look forward to the MCM upgrading epidemic management resources around the globe.”
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2021.04.21 View 6282