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Interview with Professor Kyung-Rok Yoo, Animal Biotechnology major, selected for National R&D Excellence Award

2024-01-12l Hit 311

 The study "Development of Primate Disease Models Using Gene Editing Technology" by the Animal Cell Engineering Research Team led by Professor Kyung-Rok Yoo, an animal biotechnology major in the College of Agricultural and Life Sciences at Seoul National University, has been selected as one of the 100 Best National Research and Development Achievements in 2023 by the Ministry of Science and ICT. We met with Professor Kyungrok Yoo, an animal biotechnology major, to learn more about the research.

Q. What are your thoughts on being selected as one of the Top 100 National R&D Excellence Awards in 2023?

A. I know that the National R&D Excellence 100 is a project that selects 100 outstanding achievements across science and technology, summarises them in a simple way, and delivers them to the general public. It is a great honour for me personally that my research was selected as one of the 100, and I would like to express my gratitude to the many people who helped me. In 2019, I was selected as one of the 30 R&D Excellences by the Ministry of Health and Welfare, and it seems that the Ministry of Health and Welfare has positively evaluated the research I have been doing since then on disease model development and treatment development.

Q. Please briefly describe your research on "Development of primate disease models using gene editing technology," which was selected as one of the top 100 research projects.

A. The research "Development of primate disease models using gene editing technology" selected this time is about developing "disease models" by isolating hematopoietic stem cells from primates, editing their genes using CRISPR/Cas9 technology, and transplanting them into bone marrow to study their characteristics by expressing diseases found in humans in primates. I have been studying stem cells, particularly haematopoietic stem cells, which make all the blood and immune cells in our bodies. In understanding human diseases and finding treatments, it is often difficult to conduct clinical trials directly on humans, so we create models that 'mimic' human diseases in animals to conduct preclinical trials.This experiment laid the groundwork to improve our understanding of disease through disease models so that we can move towards treating human disease. It drew on my research experience studying the preclinical characteristics of primate bone marrow transplantation, noting in particular that primates have similar haematopoietic and immune system characteristics to humans. The target of this research is a phenomenon called 'clonal haematopoiesis': three mutations commonly found in this phenomenon, DNMT3A, TET2 and ASXL1, were delivered to primate haematopoietic stem cells using CRISPR Cas9 technology and bone marrow transplants were performed to establish a disease model carrying the mutations.

Q.How did you choose this research topic?

A. Clonal haematopoiesis is a phenomenon that was first reported in a cohort study in 2014 and refers to the development and accumulation of mutations in the blood of normal people as they age. One in 10 adults over the age of 60 has this condition, and it is of interest because people with this condition are more likely to develop blood cancers or cardiovascular diseases in the future. However, because clonal hematopoiesis alone has no clinical symptoms, i.e. it is not a disease, it is difficult to directly treat humans or conduct invasive experiments such as bone marrow harvesting. Therefore, we created a model of clonal hematopoiesis in primates, which are known to be most similar to humans, and proposed an effective targeted disease experiment method to explore this condition instead of humans.In addition, there is little interest in haematology research, including hematopoietic stem cell research, in Korea, and relatively little research is being conducted. I personally heard the first report of clonal haematopoiesis while conducting haematology research in the United States, and it came as a great shock to researchers in the haematology community, including myself. Mutations in the blood do not suddenly arise, and humans only discovered clonal haematopoiesis in 2014. There must be many phenomena that have already occurred in vivo that humans have yet to discover or understand.After the first report of clonal haematopoiesis in 2014, I quickly started working on related research to properly study the field and explore potential phenomena.

Q.Were there any challenges in your research?

A. Firstly, the very subtle nature of haematopoietic stem cells made gene editing and engraftment challenging.Haematopoietic stem cells have a very high stem cell capacity because they can be transplanted into the body and live semi-permanently, but if there is even the slightest mistake in the manipulation, they lose their engraftment (the ability to be transplanted and live). This means that gene editing with CRISPR/Cas9 is difficult: you have to cut and manipulate a piece of DNA, create the conditions for successful engraftment, and then increase the efficiency of engraftment. It took a long time to optimise this process. Second, there were limitations to the primate research setting. Lastly, there are the inherent challenges of experimenting with primates. Primates live for 30-40 years and use the same instruments and antibodies to harvest and manipulate bone marrow that we use in humans, making research with them more complex than with other animals. We compensate for this by conducting joint research with the United States, which has a long history of primate research. In addition to this, it is difficult to set up primate bone marrow transplantation studies in Korea, especially during the COVID-19 outbreak in 2020, when all primates were used for COVID-19 research and it was impossible to import primates for a while. Fortunately, the supply and demand is now improving, so we are continuing to discuss with the Korea Biotechnology Institute to create a research environment where we can conduct experiments on primates in Korea.

Q. Under what conditions do you usually use primates in your experiments?

A. For this experiment, we usually use young adult primates around 3-5 years old. In humans, clonal haematopoiesis is 10-20% active in people over 60 years of age. To see if this phenomenon also occurs in primates as they age, we collected blood from 50 to 60 older primates over the age of 20. We found that older primates had mutations in their blood similar to humans, which was the first confirmation that clonal haematopoiesis occurs in primates. This result reinforced the importance of using primates to model clonal haematopoiesis.

Q. Please tell us a little bit about the other topics you are currently working on in your lab.

A. As I mentioned, I'm interested in creating animal models, and I'm also interested in research related to livestock such as cattle, pigs, and chickens, which is part of my major in animal biotechnology. In particular, I'm interested in organoids, which are cultures of cattle, pig, and chicken organs in vitro to mimic the characteristics of the organs in the body as much as possible, and to study how these organoids can be used to make livestock healthier and grow better in terms of nutrition, physiology, and disease resistance.Alongside this, I'm also interested in studying extracellular vesicles called 'exosomes'.Almost all cells secrete vesicles, or exosomes, outside of the cell that have properties similar to those of the parent cell, and these exosomes have recently gained interest in the scientific community due to the discovery that they contain substances that mirror the properties of the parent cell.The functions of exosomes are 1) disease diagnosis and 2) treatment using stem cells and immune cell exosomes.I am focusing on the therapeutic area. I am conducting research to improve the efficacy of treatment by manipulating stem cells or immune cells, and to treat diseases by enhancing exosome secretion.

Q. What are your future research directions and goals?

A. My personal goal is to actually incorporate the keyword 'convergence' into my research. My current research goals are to build and research convergent concepts by integrating my ongoing haematology research, immunology research that goes hand in hand with haematology research, and biotechnology such as organoids, exosomes, and CRISPR Cas9. In the long term, I aim to accumulate achievements and establish a platform to implement "One Health," where people, the environment, and animals pursue health in harmony. I hope to contribute to creating a future where animals and humans can lead healthy lives together.

It is also important that the graduate students under my guidance in the lab become good researchers. In my opinion, a good researcher requires not only excellent research skills, but also logical thinking skills that can objectively summarise existing research to formulate hypotheses and find complementary points, and the ability to continue research according to their research background and their own research colours. Of course, it is not easy to be perfect in every process, but I think it is most important to become a hexagonal person who is not biased towards any one area and can do everything independently even if it takes time. I hope that our graduate students will go through this process and become researchers who think, plan, and execute independently.

Q. You were elected as a member of the Younger Generation Academy of Science and Technology (Y-KAST) in recognition of your outstanding academic achievements, do you have any goals you would like to achieve as a young scientist?

A. First of all, I think it is a great honour to be elected as a member of the Y-KAST. As a young scientist, I will not rest on this honour, but will continue to actively challenge new environments or new technologies. Previously, when I was in the US, I had the opportunity to participate in an award where 10 young haematologists from across the US and Europe gathered for a year to discuss haematology research in depth. The intense research over the course of a year was stressful at times, but I think there is a lot to be gained from actively throwing yourself into new learning opportunities like this experience. The older you get, the more you can develop a comfort zone - a comfortable environment and a comfortable way of thinking - and I think the willingness to step out of this comfort zone and do new things is a key attitude to progress, both research-wise and personally. I aim to make the active pursuit of newness a life-long attitude.

Q. Do you have any advice for students of CALS who aspire to become outstanding researchers like you?

A.The world is changing rapidly, and individual values are also changing, so respect for each other is required. I try to keep up with the changes and understand the values and needs of students.

Q. Any final thoughts you'd like to share?

A. I'm currently serving as the Dean of Students at my college, and I'm getting to know the ins and outs of the school in ways that I didn't as a professor. First, I'd like to share with you a story about a parent I recently met. There was a student, Hyungjoo Na, who entered the program as a freshman in 2009 and was killed in an accident during a practicum. His father wanted the accident to be remembered by many students and professors, so he donated his life insurance proceeds to scholarships, and many students have continued their education in his honor. When I met with him recently, he shared with me how he still misses his son as if it were yesterday, even after 14 years. As an instructor at the school, it gave me a lot to think about, and I hope that students reading this article will remember him as well.

In addition to curricular programs, there are various non-curricular programs at the school, such as the headquarters, the Career Development Center, each college, and the Human Rights Center. I recommend that students actively explore non-curricular programs and get to know new people and knowledge to energize their university life. As you move on with your life, you may look back on your college experience as something that changed you. It's a short four years, so be proactive in planning your own development.