1. Research Goal
Schematic Overview of Theranostic Biomolecular Intelligence Platforms in Our Lab
We aim to develop theranostic biomolecular intelligence platforms using exosomes, proteins, aptamers, nanomaterials and their hybrids for targeting the following:
- Cancers (breast, lung, liver, brain, etc)
- Inflammatory & metabolic diseases (inflammatory bowel disease, CNS autoimmune diseases, skin inflammation, MASH, etc)
By implementing these platform technologies, we address fundamental questions across three key areas:
1) Precision Diagnostics & Therapeutics: Developing exosome (EV)-based theranostics, bioluminescence-induced dynamic therapy, CRISPR diagnostics, aptamer-guided biosensing/imaging, and smart protein delivery systems.
2) Biomarker Discovery: Identifying novel cell- and EV-surface biomarkers through proximity labeling technology.
3) Inter-organ & Intercellular Communications: Elucidating the gut–liver and gut–brain axes, as well as cell-to-cell communication networks via EVs and metabolites.
2. Research Field
The above objectives will be contributing to one or more of the following multidisciplinary areas:
2-1. Biomedicine/Nanomedicine
In vitro diagnosis and in vivo imaging of cancer/disease biomarkers with sensitively designed probes
Targeted therapy through multimodal delivery systems into cells/tissues
2-2. Biological Sciences
Library screening of aptamers/peptides/proteins/antibodies to study cell-to-cell communications and dynamics
Physiological functions related to various diseases
2-3. Bionanotechnology
Engineering biomolecules (EVs/aptamers/proteins) for disease theranostics
Designing biologic carriers for the delivery of cargos (proteins, drugs, or RNAs).
Keyword 1 (Field): Theranostics, Diagnostics, Delivery, Biosensor, Nanosensor, Bioimaging, Biomaterial
Keyword 2 (Material): Extracellular Vesicle, Exosome, Aptamer, Luciferase, Peroxidase, Therapeutic Protein
Keyword 2 (Method): Protein Delivery, Photodynamic Therapy, Proximity Labeling, BRET/FRET, ROS
3. Representative Research Achievements
3-1. Protein delivery and disease therapy using cyclized proteins and exosomes
(고리형 단백질과 엑소좀을 이용한 단백질 전달 및 질병치료 연구)
1) Overview
Despite the therapeutic potential of recombinant proteins, their cell permeabilities and stabilities remain significant challenges. Cyclized recombinant proteins can serve as universal payloads for stable and permeable delivery into cells, liposomes, and extracellular vesicles (EVs). Optimal combinatorial sequences and structures can be predicted using computation analysis or AI-guided modeling.
2) Scientific Specialty and Levels
Cyclization of proteins for delivery into cells, liposomes, and EVs
In silico simulation for membrane penetration
3) Expected Contributions & Future Direction
This strategy will be universally applicable to intercellular delivery of proteins and EVs for therapy
4) Related References
International Journal of Biological Macromolecules 2023, 252; 126520
International Journal of Molecular Sciences 2022, 23(3), 1605
3-2. Discovery of target-binding ssDNA aptamers for the development of bio(nano)sensors and molecular imaging
(바이오나노센서 및 분자이미징을 위한 표적 결합 ssDNA 압타머 발굴)
1) Overview
The traditional systematic evolution of ligands by exponential enrichment (SELEX) process is time-consuming and imperceptible
2) Scientific Specialty and Levels
Visual and straightforward monitoring platforms for the rapid discovery of small molecule-binding single-stranded DNA (ssDNA) aptamers: Gold nanoaprticle-facilitated assembly via supernatant transfer (GNP-FAST) and GNP-SELEX
A discovery platform of new aptamer ligands and surface biomarkers in live cells: FACS(or MACS)-Cell SELEX
3) Expected Contributions & Future Direction
A colorimetric SELEX platform will facilitate the rapid discovery of ssDNA aptamers against various targets and identify their wide applications in biosensing and bioassays
Cell-SELEX will elucidate developmental pathways and targeted therapy of various cell types
4) Related References
3-3. Biomarker discovery and targeted imaging of cells and EVs using surface proximity labeling technology
(막근접표지기술을 이용한 세포 및 EV의 바이오마커 발굴 및 표적 이미징)
1) Overview
To address the challenge of faint fluorescence (FL) in cell surface-targeted diagnostics, we propose an APEX2-driven proximity imaging technique and a ligand-driven enzyme-accelerated signal enhancement (L-EASE) technique to clearly visualize cancer cells or EVs.
2) Scientific Specialty and Levels
Cyclization of proteins for labeling and imaging in cells and EVs
Enzyme-mediated signal amplification
3) Expected Contributions & Future Direction
These methods will be useful as a universal visualization method with exceptional sensitivity and usability for detecting cancer cells and EVs.
4) Related References
3-4. BRET/FRET-based reporters and photodynamic therapy
(FRET or BRET 기반 리포터 개발 및 광역학 치료)
1) Overview
Fluorescence or bioluminescence resonance energy transfer (FRET or BRET) systems between biomolecules and/or nanoparticles bring new insight to detect biomolecular change with higher sensitivity and flexibility as well as light-inducible cell therapy
2) Scientific Specialty and Levels
We present bioluminescence (BL)–induced proteinaceous PDT (BLiP-PDT), through the combination of luciferase and a reactive oxygen species (ROS)–generating protein (Luc-RGP), which is self-luminescent and degradable.
Other designed probes include the sensing part (peptide substrate) and detection part (fluorescence, bioluminescence and/or their energy transferred couplers). Nanoparticles (gold, quantum dot, or polymer-based nanoparticles) have been combined with this system to enhance the sensitivity and other optical properties. This nanohybrid probe can serve as a biosensor and/or an imaging probe for targeting active proteases.
3) Expected Contributions & Future Direction
BLiP-PDT is immediately useful as a promising theranostic approach against various cancers
Protease activity profiling to address biological function of proteases in vitro and in vivo
4) Related References
3-5. Colorimetric Biosensors for determining small molecules, metabolites, and hormones in biological matrices
(생체시료내 저분자물질, 대사물질, 호르몬 측정용 비색 바이오센서)
1) Overview
Gold nanoparticle-based colorimetric biosensors for assaying enzyme activity
CRISPR-based diagnostics
FRET/BRET-based biosensors
ROS Biosensors using DNA-Protein interactions
2) Scientific Specialty and Levels
Complicate methods are formidable for the development of biosensors.
There is still a challenge in enhancing FRET/BRET efficiency to avoid high background noise signal.
Despite the implications of rapid influx and oxidation of free LMW biothiols in plasma, current methods are neither sufficiently convenient nor rapid enough to detect free LMW biothiols because free LMW biothiols are susceptible to rapid oxidation.
3) Expected Contributions & Future Directions
Colorimetric assays using gold nanoparticles (AuNPs) is valuable for determining the physiological roles of many protein activities in a rapid and simple way.
QD-FRET/BRET method is anticipated to facilitate applications for studying physiological functions of protein kinases in association with drug development.
We report a novel method for the rapid detection of plasma LMW biothiols using a bacterial redox-sensing transcription repressor protein and its operator DNA element.
4) Related References
Files & Links
Useful links
학생 사이트
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학부모 사이트
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학교 양식
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3-2. Bioluminescence-based photodynamic therapy
(생물발광 기반의 광역학 치료)