2024-01-12l Hit 1161
The study "Development of Primate Disease Models Using Gene Editing Technology" by the Animal Cell Engineering Research Team led by Professor Kyung-Rok Yu, 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 Yu, 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. The National R&D Excellence 100 program identifies and highlights 100 outstanding achievements in science and technology, presenting them in an accessible manner for the general public. I am deeply honored that my research has been recognized as one of the Top 100 achievements, and I extend my heartfelt gratitude to everyone who has supported me along the way.
In 2019, I was recognized as one of the 30 R&D Excellence recipients by the Ministry of Health and Welfare. It appears that the Ministry has continued to value my ongoing research in disease model development and therapeutic advancements since then.
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 project, “Development of Primate Disease Models Using Gene Editing Technology,” which was selected as one of the Top 100 National R&D Excellence Achievements in 2023, focuses on creating disease models by isolating hematopoietic stem cells from primates, editing their genes using CRISPR/Cas9 technology, and transplanting them into bone marrow. This approach allows us to study the characteristics of human diseases by replicating them in primates.
My research primarily centers on stem cells, particularly hematopoietic stem cells, which give rise to all blood and immune cells in the body. Conducting clinical trials directly on humans often presents significant ethical and practical challenges. Therefore, we develop animal models that mimic human diseases to conduct preclinical trials. This study establishes a foundational framework to enhance our understanding of disease mechanisms and advance therapeutic approaches for human diseases.
This research builds on my prior experience in studying the preclinical characteristics of primate bone marrow transplantation. It leverages the fact that primates share remarkable similarities with humans in their hematopoietic and immune systems. Specifically, the study targets a phenomenon called clonal hematopoiesis, which involves three commonly observed mutations: DNMT3A, TET2, and ASXL1. Using CRISPR/Cas9 technology, these mutations were introduced into primate hematopoietic stem cells, followed by bone marrow transplantation, to establish a disease model carrying these mutations.
Q. How did you choose this research topic?
A. Clonal hematopoiesis, first identified in a 2014 cohort study, refers to the accumulation of mutations in the blood of otherwise healthy individuals as they age. Approximately 10% of adults over 60 are affected, with an increased risk of developing blood cancers or cardiovascular diseases. However, as clonal hematopoiesis is asymptomatic and not classified as a disease, it is difficult to conduct direct clinical interventions or invasive experiments, such as bone marrow harvesting, in human subjects.
To address this, I developed a model of clonal hematopoiesis in primates, which are biologically similar to humans, enabling effective, targeted experiments without relying on human trials. Hematopoiesis and hematopoietic stem cell research remain relatively underexplored in Korea, with few researchers pursuing this field.
This discovery profoundly impacted the hematology research community, including myself, as it underscored that mutations in the blood do not arise suddenly but rather accumulate over time. Motivated by this realization, I began exploring clonal hematopoiesis and other phenomena that may similarly deepen our understanding of human biology.
Q.Were there any challenges in your research?
A. There were several challenges in my research. First, the subtle and delicate nature of hematopoietic stem cells made gene editing and engraftment particularly difficult. These cells have an exceptional capacity for self-renewal, allowing them to live semi-permanently after transplantation. However, even the slightest error during manipulation can cause them to lose their engraftment ability. This made CRISPR/Cas9 gene editing especially challenging, as it required precise DNA cutting, creating conditions to support engraftment, and improving engraftment efficiency—an optimization process that took considerable time.
Second, conducting primate research in Korea posed significant challenges. Primate studies are inherently complex due to their long lifespan (30–40 years) and the need for human-equivalent instruments and antibodies for bone marrow manipulation. Moreover, during the COVID-19 outbreak in 2020, primates were prioritized for pandemic-related research, which temporarily halted their availability for other studies in Korea. To overcome these difficulties, we collaborated with institutions in the United States, which have a long history and robust infrastructure for primate research. Additionally, we are actively working with the Korea Biotechnology Institute to establish a research environment that supports primate studies domestically.
Q. Under what conditions do you usually use primates in your experiments?
A. For our experiments, we typically use young adult primates aged 3–5 years. In humans, clonal hematopoiesis is observed in 10–20% of individuals over the age of 60. Since the age of primates can be roughly converted to human age by multiplying by 2.5, we analyzed blood samples from older primates aged 20 years or more, equivalent to 50–60 human years. Remarkably, we found that these older primates exhibited mutations in their blood similar to those observed in humans, marking the first confirmation that clonal hematopoiesis occurs in primates. This finding underscores the critical role of primates in modeling clonal hematopoiesis and advancing our understanding of this phenomenon.
Q. Please tell us a little bit about the other topics you are currently working on in your lab.
A. As I mentioned earlier, my research interests include creating animal models and studying livestock, such as cattle, pigs, and chickens, which align with my expertise in animal biotechnology. A key focus is on organoids—cultures of cattle, pig, and chicken organs grown in vitro to mimic the characteristics of their in vivo counterparts. These organoids allow us to study ways to improve livestock health, growth, nutrition, physiology, and disease resistance.
In addition, I am researching extracellular vesicles known as exosomes. Nearly all cells secrete exosomes, which carry properties and substances reflective of their parent cells. These vesicles have garnered significant attention for their potential in disease diagnosis and treatment. My work focuses on the therapeutic potential of exosomes, particularly those derived from stem cells and immune cells. I am exploring ways to enhance exosome secretion and manipulate these cells to improve treatment efficacy for various diseases.
Q. What are your future research directions and goals?
A. My future research directions and goals are centered on incorporating the concept of "convergence" into my work. My immediate goal is to integrate my ongoing hematology research with related fields such as immunology and cutting-edge biotechnologies, including organoids, exosomes, and CRISPR/Cas9, to build a multidisciplinary research framework. In the long term, I aim to establish a platform for implementing the "One Health" approach, which seeks to achieve harmonious health for people, animals, and the environment. Ultimately, I hope my work contributes to a future where humans and animals can lead healthier lives together.
In addition to my research, I believe that fostering capable researchers is a vital part of my role. A good researcher, in my view, must possess not only strong technical and experimental skills but also the ability to think logically, objectively summarize existing studies, formulate hypotheses, and identify ways to improve upon prior research. They should also be able to continue their research independently, bringing their unique perspective and creativity to the field. While it is challenging to excel in all aspects of research, my aim is to guide my graduate students to become well-rounded "hexagonal" researchers—those who are versatile and balanced in their abilities. I hope they will develop the skills to think critically, plan effectively, and execute their research independently, ultimately becoming leaders in their respective fields.
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 and foremost, I consider it a tremendous honor to be elected as a member of the Younger Generation Academy of Science and Technology (Y-KAST). As a young scientist, I see this recognition not as a culmination but as a starting point to continue challenging myself in new environments and embracing emerging technologies.
During my time in the United States, I had the privilege of participating in the Translational Research Training in Hematology (TRTH) program, where 10 young hematologists from across the U.S. and Europe came together for a year to deeply explore hematology research. While the program’s intensity was occasionally stressful, it offered immense opportunities for growth, fostering a collaborative and innovative research environment. This experience underscored the value of actively engaging in new learning opportunities and stepping outside of familiar surroundings.
As scientists, the older we get, the easier it becomes to settle into comfortable ways of thinking and working. However, I firmly believe that progress—both in research and personal development—requires the willingness to leave our comfort zones and embrace new challenges. My goal is to make the active pursuit of new ideas, environments, and technologies a lifelong attitude, continually driving innovation in my research and contributing meaningfully to the scientific community.
Q. Do you have any advice for students of CALS who aspire to become outstanding researchers like you?
A. The world is changing at an unprecedented pace, and with it, individual values and perspectives are evolving. My advice to students of CALS who aspire to become outstanding researchers is to cultivate respect for one another, recognizing and appreciating diverse ideas and approaches. Science thrives in an environment of collaboration and mutual understanding, and respecting the values and needs of others is essential for building such an environment.
Personally, I strive to keep up with these changes and make a conscious effort to understand the unique values, goals, and aspirations of students. By doing so, I believe we can foster a more inclusive and innovative academic community. Aspiring researchers should not only focus on technical and scientific excellence but also develop a mindset of adaptability and empathy to navigate the challenges and opportunities of our rapidly changing world.
Q. Any final thoughts you'd like to share?
A. As the current Dean of Students at my college, I have come to understand the institution in ways I hadn’t before as a professor. I’d like to share a meaningful story that has deeply impacted me. Recently, I met the father of a student, Hyungjoo Na, who tragically passed away in an accident during a practicum in 2009, just after entering as a freshman. In his memory, Hyungjoo’s father donated the proceeds from his life insurance to establish scholarships, enabling many students to continue their education in his honor. When I spoke with him recently, he shared how he still feels his son’s absence as if it were yesterday, even after 14 years. This conversation reminded me of the weight of responsibility we have as educators and mentors. I hope that students reading this article will also take a moment to remember him and the legacy he has left behind.
Beyond academics, I encourage students to actively engage with the wide range of non-curricular programs offered at the university, such as those run by the Career Development Center, individual colleges, the Human Rights Center, and other campus organizations. These opportunities allow students to meet new people, gain fresh perspectives, and energize their university experience.
College life is a transformative time that can shape who you become in the years ahead. As you move forward in life, you may look back on these four years as one of the most pivotal periods of growth and self-discovery. It is a brief chapter, so I urge you to be proactive in exploring opportunities, setting goals, and planning your personal development. Make the most of it.