한빛사 인터뷰
1. Can you please briefly summarize the paper?
Natural killer (NK) cells, as "off-the-shelf" immune effectors capable of antigen-independent activation, represent promising candidates for treating solid tumors and refractory cancers. However, their therapeutic potential is limited by short lifespan and restricted proliferation within the complex tumor microenvironment. While exogenous DNA can trigger innate immune responses in immune cells, persistent activation of cytosolic DNA sensing pathways impairs the cytotoxic efficacy of NK cells. Targeting DNA sensing may thus overcome key limitations in NK cell therapy.
This study focuses on modulating the STING pathway for cancer immunotherapy. By validating the function of Poxin?a cGAMP-specific nuclease?we engineered Poxin-expressing NK cells. Results demonstrate that Poxin expression blocks DNA-driven innate immune activation and significantly suppresses apoptosis in activated NK cells. Furthermore, Poxin enhances cytotoxicity by upregulating perforin/GZMB expression, granule release, and activating receptor levels. We also confirmed improved anti-tumor efficacy of Poxin-modified NK/CAR-NK cells in vivo. Collectively, our work elucidates how inhibiting cytosolic DNA sensing promotes NK cell function and proposes STING pathway suppression as a novel strategy of cancer immunotherapies. The innovative use of Poxin to selectively disrupt DNA sensing offers significant translational potential.
Poxin transgene enhances NK cell activity through DNA sensing inhibition
2. Can you please tell us the main difficulties you had in the laboratory work and how you overcame them?
Initially, I struggled with refining research logic and conducting in-depth problem analysis. Blindly repeating experiments drained my motivation and led to self-doubt. Dr. Kim's mentorship was instrumental in navigating these challenges?through regular discussions and extensive literature review, I gradually developed a clear research direction.
A second challenge involved language barriers during collaborations. Complex projects demanded seamless teamwork: colleagues facilitated external equipment access and sample processing; enabled transcriptomic analyses through technical support; and ensured precision in in vivo experiments with their expertise. This study's success truly reflects our team's collective dedication.
3. Please introduce your laboratory, university or organization to bio-researchers in Korea.
I conduct research at the Gene and Cell Therapy Center of the Korea Research Institute of Bioscience and Biotechnology (KRIBB) under Professor Kim's guidance. Since October 2022, our lab has operated specialized teams (Cell Therapy and RNA Research) with English as the meeting language. Over three years, we've established a mature gene & cell therapy platform.
Annually in late December, Dr. Kim hosts an open house where his family warmly welcomes us for dinner and games. This culminates in year-end reviews and new-year planning by our "Recognition Conference", held in early January, deepens mutual understanding of each member's research focus.
2024년12월27일
4. Please tell us your experiences and your thoughts related to research activities abroad.
Adapting to cultural and linguistic differences was challenging initially. I'm grateful to colleagues who assisted me with administrative tasks, travel logistics, and lab procurement.
Professor Kim profoundly shaped my doctoral journey:
1. Scientifically, his rigorous approach-from cloning techniques to research logic-built my foundational skills.
2. Professionally, he leads by example in both research and work.
3. His mantra "finishing well" emphasized responsibility: whether before extended leave or graduation, proper closure respects others and oneself.
5. Can you provide some advice for younger scientists who have plans to study abroad?
First, prioritize language proficiency to accelerate cultural integration, absorb knowledge from academic talks, and facilitate scholarly discussions. Second, safeguard mental/physical well-being?develop sustainable stress-relief habits early.
6. Future plan?
Professor Kim’s RNA course ignited my interest in this field. The rapid advancement of mRNA vaccines also prompted my exploration of circular RNA and RNA sensing. With AI now enabling cost-effective investigation of RNA complexity-and given my doctoral focus on gene therapy-I aspire to deepen my work in RNA research.
7. Do you have anything else that you would like to tell Korean scientists and students?
As an ancient Chinese poet Qu Yuan wrote: "The road ahead is long; I shall search tirelessly." Research plateaus are inevitable, yet they test our resolve. Remember: true success lies in dedicating your life to what you love. Stay passionate, stay purposeful.
#Gratitude
# diligence
# health
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