2025 G-LAMP-의생명과학연구소 국제심포지엄

의생명과학연구소

초록집

∘ 일 시: 2025년 12월 19일(금) 오전 10시 ∘ 장 소: 강원대학교 의생명과학관 B-501호 ∘ 주 관/주최: 강원대학교 G-LAMP 사업단, 의생명과학대학

2025 G-LAMP -의생명과학연구소 국제심포지엄

2025.12.19(금) 오전10시 강원대학교의생명과학관B동501호 program

Opening Session (09:50–10:00) • Opening Remark: Seo Su Ryeon (Chief, KIBB)

• Congratulatory Remark: Sun Shim Choi (Dean, College of Biomedical Science)

SESSION I – Intramural speakers (10:00–10:50) • Prof. Sunyoung Park (Department of Biomedical Technology, KNU): Next-Generation Exosome Platforms for Precision Medicine: From Diagnosis to Regenerative Therapy • Prof. Jung-Shin Lee (Department of Molecular Bioscience, KNU): Functional Modulation of Set1-COMPASS in H3K4 Methylation and Transcriptional Regulation Coffee Break SESSION II – International speakers (11:00–12:30) • Dr. Haaglim Cho (Max Planck Institute for Heart and Lung Research, Germany): Endothelial insulin resistance induced by adrenomedullin mediates obesity-associated diabetes • Prof. SeYeon Chung (Department of Biological Sciences, Lousiana State University, USA): Shaping Organs: Cytoskeleton, Cell Cycle, and Apical ECM During Tubular Organ Morphogenesis in Drosophila Lunch (Catering)

주관/주최: 강원대학교G-LAMP사업단, 의생명과학대학, 의생명과학연구소

2025 G-LAMP- 의생명과학연구소 국제심포지엄

■ 일시 : 2025 년 12 월 19 일금 ( ) 오전 10 시 ■ 장소강원대학교 의생명과학관 동

PROGRAM

B 501 호

Opening remark: Su Ryeon Seo (Chief, KIBB) Congratulatory remark: Sun Shim Choi (Dean, College of Biomedical Science)

9:50-10:00

Session Ⅰ

Intramural speakers Chair: Prof. Su Ryeon Seo (Kangwon National University)

Next-Generation Exosome Platforms for Precision Medicine: From Diagnosis to Regenerative 10:00-10:25 Therapy Prof. Sunyoung Park (College of Biomedical Science, KNU)

Functional Modulation of Set1-COMPASS in H3K4 Methylation andTranscriptional Regulation

10:25-10:50

10:50-11:00

Session Ⅱ

Coffee break

Prof. Jung-Shin Lee (College of Biomedical Science, KNU)

International speakers Chair: Prof. Sun Shim Choi (Kangwon National University)

Endothelial insulin resistance induced by adrenomedullin mediates obesity-associated diabetes

11:00-12:00

Dr. Haaglim Cho (Max Planck Institute for Heart and Lung Research, Germany)

Shaping Organs: Cytoskeleton, Cell Cycle, and Apical ECM During Tubular Organ 12:00-12:30 Morphogenesis in Drosophila Prof. SeYeon Chung (Lousiana State University, USA)

12:30-13:30

■ 주관주최 / : 강원대학교 G-LAMP 사업단의생명과학대학의생명과학연구소

Lunch (Catering)

CONTACT INFORMATION 강원대학교 의생명과학연구소 E-mail kibb@kangwon.ac.kr Tel 033-250-7262

Session Ⅰ: Intramural speakers

좌장 : 서수련 소장 (강원대학교 의생명과학연구소)

■ Next-Generation Exosome Platforms for Precision Medicine: From Diagnosis to Regenerative Therapy

Prof. Sunyoung Park (Department of Biomedical Technology, KNU)

■ Functional Modulation of Set1-COMPASS in H3K4 Methylation and Transcriptional Regulation

Prof. Jung-Shin Lee (Department of Molecular Bioscience, KNU)

박선영 교수 (강원대학교 의생명융합학부 의생명공학전공)

E-mail: sunyoungpark@kangwon.ac.kr

연세대학교 임상병리학과 박사 Ø 학위논문: Potential prognosis of miR-944 and its association with ΔNp63 in cervical cancer (연관 분야-암생물학, 분자진단학, 생물정보학)

PROFESSIONAL EXPERIENCE

연세대학교 임상병리학과 학사

강원대학교 의생명융합학부 의생명공학전공, 조교수

연세대학교 공과대학 기계공학부, 연구교수

㈜더다봄, 연구소장

연세대학교 공과대학 기계공학부, 박사후 연구원

㈜옵티팜, 연구원

국문 제목: 정밀의료를 위한 차세대 엑소좀 플랫폼: 진단에서 재생치료까지

영문 제목: Next-Generation Exosome Platforms for Precision Medicine: From Diagnosis to Regenerative Therapy

초록

발표자: Sunyoung Park (Kangwon National University)

Exosomes are nanoscale lipid-bilayer vesicles that mediate intercellular communication by transporting bioactive molecules such as nucleic acids and proteins, and they have emerged as promising candidates for regenerative medicine. Among them, salivary gland epithelial stem cell-derived exosomes (SGESC-Exos) exert antifibrotic effects in salivary gland injury models through the delivery of microRNAs, including miR-1290 and miR-3162. However, their clinical application remains limited by low production yield and particle heterogeneity. To overcome these barriers, we developed exosome-mimetic nanoparticles (ENPS) using a microfluidic platform integrated with a reverse-Tesla micromixer. This platform enables efficient mixing and self-assembly of lipid and aqueous phases, generating uniform nanoparticles with high nucleic acid encapsulation efficiency. The resulting ENPS exhibit physicochemical properties comparable to natural exosomes while displaying improved homogeneity. Functionally, ENPS demonstrated markedly enhanced therapeutic efficacy, with approximately 21-fold higher cellular uptake and a two-fold faster wound closure rate compared to SGESC-Exos. These findings highlight the potential of microfluidics-based bottom-up synthesis as a robust strategy for engineering exosomeinspired therapeutics, paving the way for clinical translation in regenerative medicine.

E-mail: jungshinlee@kangwon.ac.kr

PROFESSIONAL EXPERIENCE

2012-현재

2025-현재

2025-현재

2021-현재

2015-현재

2014-현재

이정신 교수 (강원대학교 분자생명과학과)

이학박사, 서울대학교 생명과학부

이학석사, 서울대학교 미생물학과

이학사, 서울대학교 미생물학과

강원대학교 조교수, 부교수, 교수

국립강원전문과학관 비상임이사

한국유전체학회 이사

Molecules and Cells 편집위원

Journal of Microbiology 편집위원

Journal of Microbiology and Biotechnology 편집위원

한국분자세포생물학회 운영위원장

Functional Modulation of Set1-COMPASS in H3K4 Methylation

and Transcriptional Regulation

Jung-Shin Lee

Department of Molecular Bioscience, Kangwon National University, Chuncheon 24341, Korea

Histone H3 lysine 4 methylation (H3K4me) is a well-established marker of active transcription and is primarily catalyzed by the Set1-COMPASS complex. In this seminar, I will present findings from three related studies that uncover how specific components of Set1-COMPASS regulate H3K4 methylation and contribute to gene expression control, using Saccharomyces cerevisiae and Candida albicans as model organisms.

In S. cerevisiae, we found that H2B monoubiquitination (H2Bub1) by the E2 enzyme Rad6 is critical for H3K4 di- and trimethylation. Our CHIP-seq analysis revealed that the recruitment of Set1-COMPASS—particularly the Swd2 subunit—to chromatin depends on H2Bub1, enabling proper localization to gene promoters and accurate H3K4 methylation. Furthermore, we discovered that N-terminal acetylation, mediated by the NatA acetyltransferase, modulates Set1-COMPASS activity. Loss of NatA leads to a global reduction in H3K4me3 and redistribution of H3K4me2, highlighting the role of protein

acetylation in fine-tuning histone methylation. In C. albicans, deletion of Set1 results in premature activation of inducible genes even without external signals. Interestingly, early transcriptional activation is primarily driven by H3K4 acetylation, with H3K4 methylation accumulating later to stabilize expression. This

temporal switch from acetylation to methylation underscores the dynamic role of Set1-COMPASS in regulating inducible gene expression. Together, these studies highlight the multifaceted roles of Set1-COMPASS components in chromatin regulation and demonstrate how histone modifications are integrated to orchestrate precise transcriptional responses.

Session Ⅱ: International speakers

좌장 : 최선심 학장 (강원대학교 의생명과학대학)

■ Endothelial insulin resistance induced by adrenomedullin mediates obesity-associated diabetes

Dr. Haaglim Cho (Max Planck Institute for Heart and Lung Research, Germany)

■ Shaping Organs: Cytoskeleton, Cell Cycle, and Apical ECM During Tubular

Organ Morphogenesis in Drosophila

Prof. SeYeon Chung (Department of Biological Sciences, Lousiana State University, USA)

조학림 박사

(Max Planck Institute for Heart and Lung Research, Germany)

E-mail: Haaglim.Cho@mpi-bn.mpg.de

2022-present

PHD in Life Science School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Korea Supervisor: Prof. Darren Reece Williams

Master's in Medical and Biosciences Department of Medical and Biosciences, Kangwon National University (KNU), Korea Supervisor: Prof. Cheol Ahn

RESEARCH AND PROFESSIONAL EXPERIENCE

Senior and Principal Research Scientist Department of Pharmacology/Max-Planck Institute for Heart and Lung Research, W. G. Kerckhoff Institute, Germany

Postdoctoral Research Scientist Department of Pharmacology/Max-Planck Institute for Heart and 2019 - 2022 Lung Research, W. G. Kerckhoff Institute, Germany Supervisor: Prof. Stefan Offermanns

Postdoctoral Research Scientist School of Life Sciences, Gwangju Institute of Science and Tech (GIST), Korea Supervisor: Prof. Darren Reece Williams and Prof. Da-Woon Jung

METABOLISM

Endothelial insulin resistance induced by adrenomedullin mediates obesity-associated diabetes.

Haaglim Cho1,7, Chien-Cheng Lai1, Rémy Bonnavion1, Wessam Alnouri1, ShengPeng Wang2, Kenneth Roquid1, Hruya Kawase1, Diana Campos3, Min Chen4, Lee S. Weinstein4, Alfredo

Martínez5, Mario Looso6,7, Miloslav Sanda3, and Stefan Offermanns1,2,7,8,9

1Max Planck Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany. 2Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China. 3Max Planck Institute for Heart and Lung 4Metabolic Disease Research, Biomolecular Mass Spectrometry, Bad Nauheim, Germany. Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. 5Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain. 6Max Planck Institute for Heart and Lung Research, Bioinformatics, Bad Nauheim, Germany. 7Cardiopulmonary Institute (CPI), Bad Nauheim, Germany. 8Center forMolecular Medicine, Goethe University Frankfurt, Frankfurt, Germany. 9German Center for Cardiovascular Research (DZHK), partner site Frankfurt/Rhine-Main, Bad Nauheim, Germany.

Insulin resistance is a hallmark of obesity-associated type 2 diabetes and has classically been attributed to defects within metabolic target organs such as liver, skeletal muscle, and white adipose tissue. However, insulin must also act on the vascular endothelium to promote insulin

transport, endothelial nitric oxide synthase (ENOS) activation, nitric oxide (NO)–mediated vasodilation, and perfusion of insulin target tissues. Here, we identify endothelial adrenomedullin/Gs signaling as a critical negative regulator of endothelial and systemic insulin sensitivity. Plasma adrenomedullin levels were increased in obese humans and mice. In human umbilical vein endothelial cells, activation of Gs-coupled receptors inhibited, whereas knockdown of the Gαs subunit enhanced, insulin signaling. We identified the adrenomedullin

receptor Calcrl, a Gs-coupled GPCR, as a key mediator of this inhibitory effect. Adrenomedullin–Calcrl–Gs signaling increased proteintyrosine phosphatase 1B activity in a protein kinase A–dependent manner, leading to dephosphorylation of the insulin receptor, impaired ENOS activation, and reduced NO formation. Mice with inducible, endotheliumspecific deficiency of Gαs, Calcrl, or adrenomedullin displayed improved glucose tolerance, whole-body

insulin sensitivity, and insulin-induced signaling when fed a high-fat diet, without changes in body weight or food intake. These improvements were associated with enhanced insulin-induced ENOS activation, vasodilation, and perfusion of insulin target organs, including skeletal muscle. Conversely, adrenomedullin administration to mice mimicked the effects of obesity and induced endothelial and systemic insulin resistance, whereas endothelial loss or

blockade of the adrenomedullin receptor protected against obesity-induced insulin resistance. Thus, obesity-induced type 2 diabetes involves endothelial insulin resistance driven by the endothelial adrenomedullin/Calcrl–Gs–PTP1B axis, and inhibition of this pathway represents a potential therapeutic strategy to improve insulin sensitivity in obesity-associated type 2 diabetes

정세연 교수

(Department of Biological Sciences, Lousiana State University, USA)

E-mail: seyeonchung@lsu.edu

Feb 2006

Feb 2001

Feb 1999

Ph.D. in Biological Sciences Seoul National University, Seoul, Korea Advisor: Dr. Jeongbin Yim Thesis project: Roles of a novel gene target of wingless in the planar cell polarity and in patterning of the Drosophila wing M.S. in Biological Sciences Seoul National University, Seoul, Korea Advisor: Dr. Jeongbin Yim Thesis project: Identification and characterization of a novel gene functioning in the Notch pathway in Drosophila wing development

B.S. in Microbiology, Magma Cum Laude Seoul National University, Seoul, Korea

RESEARCH AND PROFESSIONAL EXPERIENCE

Associate Professor 08/2023 – Present Department of Biological Sciences, Louisiana State University, Baton Rouge, LA Assistant Professor 08/2017 – 08/2023 Department of Biological Sciences, Louisiana State University, Baton Rouge, LA

Research Associate (Non-tenure track faculty) Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 03/2013 – 08/2017 Advisor: Dr. Deborah J. Andrew Projects: Understanding how human disease genes act using Drosophila as a model system & how an epithelial sheet makes a three-dimensional tube Postdoctoral Fellow Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 10/2006 – 02/2013 Advisor: Dr. Deborah J. Andrew Projects: Transcriptional cascade and apical membrane dynamics during epithelial tube formation

Visiting Graduate Student Department of Biology, University of Virginia, Charlottesville, VA Advisor: Dr. Paul N. Adler Project: Characterization of a novel component in the planar cell polarity pathway Undergraduate Research Assistant Samsung medical center, Seoul, Korea Advisor: Dr. Jeho Lee Project: Cloning from human cancer tissues

Shaping Organs: Cytoskeleton, Cell Cycle, and Apical ECM During Tubular Organ Morphogenesis in Drosophila

SeYeon Chung

Department of Biological Sciences, Louisiana State University, Baton Rouge, LA, USA

Organ formation requires tight coordination between cell cycle regulation, cytoskeletal dynamics, and extracellular matrix organization. Using the Drosophila embryonic salivary gland (SG) as a model, we examine how these processes integrate to drive epithelial tube morphogenesis.

We first show how Rho1-dependent actomyosin contractility generates the forces for apical constriction during SG invagination. The GPCR Smog transduces the Folded gastrulation (Fog) signal to promote Rho kinase accumulation and myosin activation at the medioapical cortex. Beyond its Fog-dependent function, Smog also contributes to epithelial integrity and cortical actin organization, revealing distinct ligand-dependent roles in regulating myosin pools during morphogenesis.

Next, we define the role of the SP1/KLF transcription factor Huckebein (Hkb) in linking transcriptional control to cell cycle state. Loss of hkb disrupts the normal endoreplication program, causing aberrant cell division, apoptosis, and defects in SG size and positioning. Hkb represses key cell cycle and pro-apoptotic genes, and modulating cyclin E, CDK1, or fizzy-related partially rescues these defects, demonstrating Hkb’s central role in coordinating proliferation with tissue morphogenesis.

Finally, we identify the sulfation enzyme Papss as a critical regulator of apical extracellular matrix (AECM) organization and lumen expansion. Papss mutants display a condensed AECM, disrupted apical membranes, and traXicking defects. Papss activity is required for proper localization of the ZP-domain proteins Piopio and Dumpy, whose loss leads to luminal constrictions and irregular tube shape.

Together, these findings reveal how GPCR signaling, transcriptional regulation, and sulfation-dependent AECM assembly converge to control the mechanical and structural events that drive tubular organ formation.

■ Development and Optimization of Lyophilized FGF Formulation via Design of Experiment (DOE): Formulation Strategy for Stability

유혜원 (바이오헬스융합학과)

■ Development of Genetically Engineered Feeder Cells Expressing Ecto-Calreticulin for NK Cell Expansion 홍혜진 (분자의생명융합학과)

■ Effect of direct cell to cell communication between mesodermal lineage cell and mesenchymal stem cell on the immunomodulation and regeneration 김지섭 (시스템면역과학과)

■ Local Gene Silencing with ROS-Responsive Verteporfin Nanoparticles to Promote Scarless Chronic Wound Healing

Khanh Linh Thi Nguyen (의생명과학과)

■ Polycomb-targeted transcription factor genes remain active despite promoter hypermethylation in colorectal cancer

권민경 (분자의생명융합학과)

■ RCAN1 as a Key Regulator of RIPK1–RIPK3–MLKL-Mediated Necroptosis

김희수 (분자의생명융합학과)

■ Re-Evaluating the Synthetic Intermediate 5-Hydroxy-4-methoxy-2-nitrobenzoic Acid (HMN) for Its Anti-Inflammatory Potentia

임대현 (분자생명융합학과)

■ Swd2/Cps35 determines H3K4 tri-methylation via interactions with Set1 and Rad6

김동현 (의생명과학과 분자생명과학전공)

■ Therapeutic Potential of Peiminine as a Natural STING Antagonist Against Neuroinflammatory Disordersy

김선숙 (생명과학연구소)

유혜원 (석사4, 바이오헬스융합학과)

Development and Optimization of Lyophilized FGF Formulation via Design of Experiment (DOE): Formulation Strategy for Stability

Yu Hye – Won

Department of Bio-Health Convergence Graduate School, Kangwon National University

Abstract

The aim of this study was to improve the storage stability of Fibroblast Growth Factor-1 (FGF1), a member of the FGF family with inherent instability, by developing a lyophilized formulation and optimizing the combination of stabilizing excipients. To achieve this, a stepwise Design of Experiments (DOE) strategy was employed. In the screening phase, a Plackett–Burman design (PBD) was used to identify excipients that significantly affected the post-lyophilization content recovery of FGF1 (Y₁, %); trehalose (Tre), Tween 80 (Twe), and mannitol (Man) were selected as critical factors. In the subsequent optimization phase, a Box–Behnken design (BBD) was applied to define the design space and to propose an optimal stabilizer composition. The initially suggested optimal point recommended mannitol at 1%, but practical evaluation of the lyophilized cakes showed that at least 6% mannitol was required to ensure acceptable physical stability. After re-optimization with this experimental constraint, formulation F6 (7% mannitol, 4.2% trehalose, 0.2% Tween 80) was selected; although its composite desirability was slightly lower than the theoretical optimum, it was more appropriate in terms of cake integrity and handling. Model verification showed excellent agreement between predicted and experimental values, with prediction accuracies of 99.4% for content recovery and 97.2% for reconstitution time. ELISA and cell-proliferation assays further confirmed that antigen-binding capacity and mitogenic activity were preserved after lyophilization of the F6 formulation. Stability testing at 25 ± 5 °C for 0, 14, and 28 days demonstrated that F6 maintained higher content recovery and binding affinity than the liquid control, the lyophilized control without stabilizers, and the non-optimized formulation. Collectively, these results indicate that the lyophilized formulation developed in this study is an effective strategy to maintain the biological activity of FGF1, and that a DOE-based multi-response optimization approach can be extended to other FGFS and protein therapeutics that are sensitive to moisture and heat.

□keywords

FGF, Lyophilization, Stability, Stabilizer, DOE, Optimization

홍혜진 (석사3, 분자의생명융합학과)

Development of Genetically Engineered Feeder Cells Expressing Ecto-Calreticulin for NK Cell Expansion

NK cells, offering intrinsic cytotoxicity and unique mechanisms distinct from T cells, are used in adoptive cell therapy as a promising strategy for cancer treatment. Nevertheless, their limited in vivo frequency and the difficulty of achieving large-scale, efficient ex vivo expansion remain major challenges. During the NK cell expansion process, feeder cells promote NK cell activation and proliferation through surface receptor–ligand interactions, and alterations in these ligands may influence expansion efficiency. However, this aspect has not

been sufficiently investigated. Therefore, This study aimed to identify key factors involved in NK cell expansion using feeder cells to promote more efficient proliferation. To this end, K562 feeder cells were subjected to irradiation, chemotherapeutic drug treatment, or heat shock to induce cellular stress, and then co-cultured with PBMCS. As a result, NK cells were selectively expanded under all three conditions. Analysis of stress ligand expression in K562 feeder cells

revealed a consistent increase in calreticulin expression, which showed a significant correlation with NK cell proliferation. These findings suggest that utilizing K562 feeder cells expressing calreticulin can effectively promote NK cell expansion and may contribute to the development of NK cell-based immunotherapies. Based on these results, we are developing K562 feeder cells overexpressing calreticulin to further enhance NK cell expansion efficiency.

김지섭 (통합6, 시스템면역과학과)

Effect of direct cell to cell communication between mesodermal lineage cell and mesenchymal stem cell on the immunomodulation and regeneration

Ji-Seob Kim1, Seo-Jeong Kim1, Min-Hee Moon1, Hae-Dam Park1, In-Sun

Hwang2 and Byung-Hyun Cha1, 2*

1Department of Systems Immunology, Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Korea, 2Institute of Bioscience & Biotechnology, Kangwon National University, Korea

Cell‐to‐cell communication is essential for tissue development, homeostasis, and the maintenance of cellular functions after injury. There are a variety of means by which cells communicate; these include exosomes, secreted microRNAs, tunneling nanotubes (TNTS) or gap junctions. We confirmed that cellular material exchange occurred through direct contact between mesenchymal stem cells (MSCS) and mesodermal lineage cells (MLCS) during a 48-hour co-culture time. We obtained MSC altered by microenvironment of MLC generated via a time-dependent co-culture method with green/red fluorescent cell trackers, and we termed microenvironment-MLC-transferred MSCS (mi-MLC-MSCS). we characterized the sorted mi-MLC-MSCS through flow cytometry, immunocytochemistry, and RNA-seq–based transcriptomic analysis. mi-MLC-MSCS exhibited dramatic genetic changes in just 48 hours, and increased expression of genes associated with anti-inflammatory activity and tissue regeneration. They also showed higher proliferative potential and wound healing capacity than conventional MSCS. These findings suggest that cellular material exchange occurred through direct contact of MSCS with MLCS positively influences tissue regeneration and may be harnessed for the development of novel therapeutic strategies.

Khanh Linh Thi Nguyen (석사1, 의생명과학과)

Local Gene Silencing with ROS-Responsive Verteporfin Nanoparticles to Promote Scarless Chronic Wound Healing

Khanh Linh Thi Nguyen1 , Hoai-Thuong Duc Bui1, Hyuk Sang Yoo1,2,3*

1Department of Medical Biomaterial Engineering, College of Biomedical Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea. 2Institute for Molecular Science and Fusion Technology, Kangwon National University 3Institute of Bioscience and Biotechnology, Kangwon National University . * corresponding author’s E-mail: hsyoo@kangwon.ac.kr

Delayed healing of chronic burn wounds is a severe complication in infected burn patients, primarily due to persistent infection and impared immune response. Specifically, overexpression of matrix metalloproteinases (MMPS) is a significant factor in the prolonged healing. Here, a nanoflatform is proposed for SIRNA delivery and wound healing via silencing MMP-9 expression and reducing

excessive scarring. Multiarmed poly(ethylene glycol) (PEG) is conjugated with linear poly(ethyleneimine) (LPEI), and verteporfin through a ROS-responsive linker (selenocystamine). These PEG conjugates self-assemble into nanoparticles and are subsequently complexed with SIRNA. After administration to the burn wounds, near infrared (NIR) light is applied to activate verteporfin and create a ROS-response release profile. The remaining complex continues to deliver SIRNA to the

target cells for MMP-9 silencing. We used PEGFP as a model gene for prelimentary investigation. Our LPEI-PEG-PEGFP complex at an ratio N/P of 10 showed efficient DNA condensation and high transfection efficiency on HEK293 after 24 h. Meanwhile, when treating LPEI-PEG-Ve with an oxidizing agent (H2O2), the drugs were gradually released from the conjugates over 2 h.

Polycomb-targeted transcription factor genes remain active despite promoter hypermethylation in colorectal cancer

Min-Kyeong Kwon1, Goeun Park1, Dayoung Go1, and Sun Shim Choi1*

권민경 (석사3, 분자의생명융합학과)

1Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, Korea *Corresponding author: schoi@kangwon.ac.kr

DNA methylation is a key epigenetic regulator often disrupted in cancer, yet how promoter methylation dynamics translate into transcriptional changes during cancer progression remains incompletely understood. Here, we employed targeted bisulfite sequencing and RNA-seq on paired tumor and non-tumor tissues from 80 Korean colorectal cancer (CRC) patients to map promoter methylation and gene expression dynamics. Promoters with high baseline methylation in non-tumor tissues tended to become hypomethylated in tumors, while those with low baseline methylation underwent partial hypermethylation. However, these changes did not consistently correlate with gene silencing or activation. Strikingly, promoters marked by Polycomb (PCG⁺) in non-tumor tissue were prone to hypermethylation yet often remained transcriptionally active in tumors, a paradox most prominent in transcription factor (TF) genes. In contrast, hypermethylation in PCG⁻ promoters was more consistently associated with transcriptional repression. Our findings suggest that epigenetic plasticity at PCG⁺ TF gene promoters can override the typically repressive effects of DNA methylation, potentially enabling tumors to maintain or enhance the expression of key regulatory genes. This highlights the importance of PCG occupancy in shaping the functional consequences of methylation changes during colorectal tumorigenesis, warranting deeper investigation into how these epigenetic adaptations drive cancer progression.

김희수 (석사4, 분자의생명융합학부)

RCAN1 as a Key Regulator of RIPK1–RIPK3–MLKL-Mediated Necroptosis

Necroptosis is a caspase-independent form of programmed cell death initiated by tumor necrosis factor-α (TNF-α) signaling under conditions of caspase inhibition and mediated by the RIPK1–RIPK3–MLKL axis. Activation of this pathway leads to MLKL phosphorylation and

oligomerization, plasma membrane disruption, and the release of pro-inflammatory mediators, thereby contributing to excessive inflammation in various pathological contexts. However, endogenous regulatory mechanisms that fine-tune necroptotic signaling remain incompletely defined. Regulator of calcineurin 1 (RCAN1) is an intrinsic modulator of calcineurin activity that is dynamically regulated under stress conditions, but its role in necroptosis has not been elucidated. In this study, we investigated whether RCAN1

functions as a regulatory factor in necroptosis based on preliminary evidence suggesting a potential interaction between RCAN1 and RIPK1. Using mouse embryonic fibroblasts (MEFS) with distinct RCAN1 genotypes, we found that Rcan1-deficient cells exhibited enhanced

phosphorylation of RIPK1, RIPK3, and MLKL, along with increased MLKL oligomerization and heightened necroptotic cell death. In contrast, RCAN1-transgenic cells showed attenuated signaling activation and reduced sensitivity to necroptosis under the same conditions. Pharmacological inhibition of calcineurin partially reproduced the hyperactivation phenotype observed in RCAN1-deficient cells, suggesting that RCAN1-mediated regulation of necroptosis is linked to calcineurin signaling. Together, these findings identify RCAN1 as an

endogenous suppressor of the RIPK1–RIPK3–MLKL pathway and reveal a previously unrecognized role of the RCAN1–calcineurin axis in the regulation of necroptosis.

임대현 (석사2, 분자의생명융합학과)

Re-Evaluating the Synthetic Intermediate 5-Hydroxy-4-methoxy-2-nitrobenzoic Acid (HMN) for Its Anti-Inflammatory Potential

Inflammation serves as a fundamental host defense mechanism that promotes tissue repair and restores physiological balance following pathogenic invasion or tissue damage. While this response is typically self-limited, inadequate resolution can drive the transition to chronic inflammation, which is

closely associated with the development and progression of various diseases, including cancer, metabolic dysfunction, and neurodegenerative disorders. Accordingly, elucidating the regulatory pathways governing inflammatory responses and identifying agents capable of modulating these pathways are of growing therapeutic importance.

In the present study, we examined the anti-inflammatory potential of 5-Hydroxy-4-methoxy-2-nitrobenzoic acid (HMN), a compound widely recognized as an intermediate in the synthetic route of gefitinib. Considering that chemical intermediates used in drug synthesis may

harbor uncharacterized biological activities, we applied a repurposing-driven approach to evaluate HMN as a bioactive molecule. Using LPS-stimulated RAW264.7 macrophages, we found that HMN markedly attenuated the expression of pro-inflammatory mediators, including COX-2, INOS, TNF-α, pro-IL-1β, and IL-6 at the transcriptional level. HMN also suppressed nuclear translocation of NF-κB p65, accompanied by reduced protein levels of COX-2, INOS, and pro-IL-1β, demonstrating its

inhibitory capacity on inflammatory signaling.

Collectively, our findings reveal that HMN possesses intrinsic anti-inflammatory properties and may represent a promising candidate for therapeutic development. This work emphasizes that synthetic intermediates, beyond their traditional chemical roles, can exhibit distinct pharmacological activities

offering new opportunities for intermediate-based drug discovery and repurposing strategies.

김동현 (박사2, 의생명과학과 분자생명과학전공)

Swd2/Cps35 determines H3K4 tri-methylation via interactions with Set1 and Rad6

Histone H3K4 trimethylation (H3K4me3) is a hallmark of active transcription, established by the Set1/COMPASS complex through a mechanism that requires prior histone H2B monoubiquitination (H2Bub). While Swd2 is known to bridge these two epigenetic marks, the functional interplay between Rad6, Set1, and Swd2 remains to be fully elucidated. This study utilized genome-wide occupancy profiling to investigate how Rad6 and Set1 dictate the spatial distribution of Swd2. Our

results reveal that Swd2 typically occupies both the 5' and 3' regions of genes, associating with Set1 and the cleavage and polyadenylation factor (CPF), respectively. Notably, the loss of Rad6-mediated H2Bub completely abolished Swd2’s chromatin binding across the genome. Furthermore, in the absence of Set1, Swd2 failed to localize at the 5' region and instead showed increased enrichment at the 3' region. These findings demonstrate that Rad6 is indispensable for

the initial recruitment of Swd2 to transcribed genes, while Set1 functions to redistribute Swd2 toward the 5' region to facilitate site-specific H3K4me3.

김선숙 (연구교수, 의생명과학연구소)

Therapeutic Potential of Peiminine as a Natural STING Antagonist Against Neuroinflammatory Disorders

SoJin Cha1,Seon Sook Kim2and Su Ryeon Seo1,3*

1 Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon, 24341, Republic of Korea 2 Institute of Life Science, Kangwon National University, Chuncheon, 24341, Republic of Korea 3 Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, 24341, Republic of Korea

Abstract: Aberrant STING signaling is closely linked to neuroinflammation and the progression of neurodegeneration. Here, we identify peiminine, a natural component of Fritillaria thunbergii, as a novel modulator of the STING pathway. We found that peiminine effectively inhibits the activation of downstream effectors, including TBK1, IRF3, and NF-κB, in activated microglia. This inhibition leads to a marked reduction in inflammatory mediators and facilitates a shift towards the neuroprotective M2 microglial phenotype. Furthermore, in a murine model of neuroinflammation, peiminine treatment successfully attenuated brain inflammation and prevented neurotoxicity induced by microglial activation. These data highlight the capacity of peiminine to dampen pathological STING activation, positioning it as a promising candidate for the treatment of STING-associated neurodegenerative pathologies.