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Chang Han Lee

Seoul National University · Medicine

About the Lab

Professor Chang Han Lee's research lab specializes in the rational design of therapeutic proteins and RNA-based therapeutics, with a focus on enhancing pharmacokinetics, improving target specificity, and minimizing off-target effects. The lab develops engineered antibody Fc variants with optimized pH-dependent binding to the neonatal Fc receptor (FcRn) for prolonged half-life, explores synthetic kringle domains as targeted protein therapeutics for cancer, and pioneers novel siRNA structures (asiRNA) to overcome limitations of conventional RNAi. The lab also investigates chaperone-substrate interactions and immune responses to SARS-CoV-2, integrating structural biology, synthetic biology, and translational immunology.

protein engineeringRNAi therapeuticsFc receptor bindingkringle domainantibody half-life

Research Overview

Papers
121
Total Citations
1,557
Papers (5y)
36
Primary Field
Medicine

Research Output Trend

Figures are computed from collected data and may differ slightly.

Publications per year (5y)
36total
2022
2023
2024
2025
2026
Citations per year (5y)
179total
20222023202420252026

Selected Papers

15
1
Article|150 citations·2017
IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions
Chang‐Han Lee, Gabrielle Romain, Wupeng Yan, Makiko Watanabe, Wissam Charab, Biliana Todorova, Jiwon Lee, Kendra Triplett, Moses Donkor, Oana I. Lungu, Anja Lux, Nicholas Marshall
SJR Q1Nature ImmunologyOA
Radiology, Nuclear Medicine and ImagingMedicine
2
Article|94 citations·2019
An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence
Chang‐Han Lee, Tae Hyun Kang, Ophélie Godon, Makiko Watanabe, George Delidakis, Caitlin M. Gillis, Delphine Sterlin, David Hardy, Michel Cogné, Lynn E. Macdonald, Andrew Murphy, Naxin Tu
SJR Q1Nature CommunicationsOA

The pharmacokinetic properties of antibodies are largely dictated by the pH-dependent binding of the IgG fragment crystallizable (Fc) domain to the human neonatal Fc receptor (hFcRn). Engineered Fc domains that confer a longer circulation half-life by virtue of more favorable pH-dependent binding to hFcRn are of great therapeutic interest. Here we developed a pH Toggle switch Fc variant containing the L309D/Q311H/N434S (DHS) substitutions, which exhibits markedly improved pharmacokinetics relati

Radiology, Nuclear Medicine and ImagingMedicine
3
Article|43 citations·2010
Engineering of a human kringle domain into agonistic and antagonistic binding proteins functioning in vitro and in vivo
Chang‐Han Lee, Kyung-Jin Park, Eun-Sil Sung, Aeyung Kim, Jida Choi, Jeong‐Sun Kim, Soohyun Kim, Myung‐Hee Kwon, Yong‐Sung Kim
SJR Q1Proceedings of the National Academy of Sciences

Here, we report the development of target-specific binding proteins based on the kringle domain (KD) ( approximately 80 residues), a ubiquitous modular structural unit occurring across eukaryotic species. By exploiting the highly conserved backbone folding by core residues, but using extensive sequence variations in the seven loop regions of naturally occurring human KDs, we generated a synthetic KD library on the yeast cell surface by randomizing 45 residues in the loops of a human KD template.

Radiology, Nuclear Medicine and ImagingMedicine
4
Article|17 citations·2009
Expression of soluble and functional human neonatal Fc receptor in Pichia pastoris
Chang‐Han Lee, Dong-Ki Choi, Hye‐Ji Choi, Moo-Young Song, Yong‐Sung Kim
SJR Q3Protein Expression and Purification
Radiology, Nuclear Medicine and ImagingMedicine
5
Article|16 citations·2018
Electrostatic interactions are important for chaperone–client interaction in vivo
Chang‐Han Lee, Hyunhee Kim, James C.A. Bardwell
SJR Q2Microbiology

It has long been thought that chaperones are primarily attracted to their clients through the hydrophobic effect. However, in in vitro studies on the interaction between the chaperone Spy and its substrate Im7, we recently showed that long-range electrostatic interactions also play a key role. Spy functions in the periplasm of Gram-negative bacteria, which is surrounded by a permeable outer membrane. The ionic conditions in the periplasm therefore closely mimic those in the media, which allowed

Molecular BiologyBiochemistry, Genetics and Molecular Biology
6
Article|15 citations·2011
Generation of Bivalent and Bispecific Kringle Single Domains by Loop Grafting as Potent Agonists against Death Receptors 4 and 5
Chang‐Han Lee, Kyung-Jin Park, Sang Jick Kim, Ohsuk Kwon, Ki Jun Jeong, Ayeung Kim, Yong‐Sung Kim
SJR Q1Journal of Molecular Biology
Radiology, Nuclear Medicine and ImagingMedicine
7
Article|14 citations·2022
Distinct Immune Response at 1 Year Post-COVID-19 According to Disease Severity
Chang Kyung Kang, Minji Kim, Jisu Hong, Gwanghun Kim, Soojin Lee, Euijin Chang, Pyoeng Gyun Choe, Nam Joong Kim, Ik Soo Kim, Jun-Young Seo, Daesub Song, Dong‐Sup Lee
SJR Q1Frontiers in ImmunologyOA

Background: Despite the fact of ongoing worldwide vaccination programs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding longevity, breadth, and type of immune response to coronavirus disease-19 (COVID-19) is still important to optimize the vaccination strategy and estimate the risk of reinfection. Therefore, we performed thorough immunological assessments 1 year post-COVID-19 with different severity. Methods: We analyzed peripheral blood mononuclear cells and plasm

Infectious DiseasesMedicine
8
Article|8 citations·2011
Selection and Optimization of Asymmetric siRNA Targeting the Human c-MET Gene
Seul-gi Jo, Sun Woo Hong, Jae Wook Yoo, Chang‐Han Lee, Sera Kim, Soyoun Kim, Dong-ki Lee
SJR Q1Molecules and CellsOA

The silencing of specific oncogenes via RNA interference (RNAi) holds great promise for the future of cancer therapy. RNAi is commonly carried out using small interfering RNA (siRNA) composed of a 19 bp duplex region with a 2-nucleotide overhang at each 3' end. This classical siRNA structure, however, can trigger non-specific effects, which has hampered the development of specific and safe RNAi therapeutics. Previously, we developed a novel siRNA structure, called asymmetric shorter-duplex siRNA

Molecular BiologyBiochemistry, Genetics and Molecular Biology
9
Article|8 citations·2015
Ultrasonographic Diagnosis of Non-displaced Avulsion Fracture of the Acromion: A Case Report
Chang‐Han Lee, Young‐Ah Choi, Shi-Uk Lee
SJR Q1Annals of Rehabilitation MedicineOA

Avulsion fracture of the acromion is rare. It is difficult to diagnosis because there is little displacement and it occurs even without direct trauma. We experienced a case without direct trauma that was diagnosed with ultrasonography. A 55-year-old male patient visited our outpatient clinic with shoulder pain resulting from a significant stress at the trapezius muscle during lifting of a steel reinforcement. Simple radiography revealed a calcific deposit over the acromion rather than a fracture

EpidemiologyMedicine
10
Article|8 citations·2005
A study on the etiologic factors of early childhood caries in 18-month old infants
Chang‐Han Lee, Jae-Moon Kim, Shin Kim, Tae-Sung Jeong
THE JOURNAL OF THE KOREAN ACADEMY OF PEDTATRIC DENTISTRY

For the purpose of investigating the etiologic factors of early childhood caries in 18-month old infants which is an important period in pediatric dentistry, 234 infants of 18-month age and their first care-givers (mothers in most cases) who visited Ilsin Christian Hospital in Busan for the baby-care counseling and vaccination were examined. The oral examination was performed on the infants and their care-givers were individually interviewed about various items, and the data was statistically pr

Nutrition and DieteticsNursing
11
erratum|7 citations·2017
Erratum: Corrigendum: IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions
Chang‐Han Lee, Gabrielle Romain, Wupeng Yan, Makiko Watanabe, Wissam Charab, Biliana Todorova, Jiwon Lee, Kendra Triplett, Moses Donkor, Oana I. Lungu, Anja Lux, Nicholas Marshall
SJR Q1Nature ImmunologyOA
Radiology, Nuclear Medicine and ImagingMedicine
12
Article|6 citations·2021
Engineering IgG1 Fc Domains That Activate the Complement System
Chang‐Han Lee, George Delidakis
SJR Q4Methods in molecular biology
ImmunologyImmunology and Microbiology
13
Article|5 citations·2024
Novel FRET‐based Immunological Synapse Biosensor for the Prediction of Chimeric Antigen Receptor‐T Cell Function
Hae Nim Lee, Soojin Lee, Jisu Hong, Hyejin Yoo, Jiyun Jeong, Yong‐Woo Kim, Hyun Mu Shin, Mihue Jang, Chang‐Han Lee, Hang‐Rae Kim, Jihye Seong
SJR Q1Small MethodsOA

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment. CARs are activated at the immunological synapse (IS) when their single-chain variable fragment (scFv) domain engages with an antigen, allowing them to directly eliminate cancer cells. Here, an innovative IS biosensor based on fluorescence resonance energy transfer (FRET) for the real-time assessment of CAR-IS architecture and signaling competence is presented. Using this biosensor, scFv variants for mesothelin-ta

OncologyMedicine
14
erratum|5 citations·2019
Publisher Correction: An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence
Chang‐Han Lee, Tae Hyun Kang, Ophélie Godon, Makiko Watanabe, George Delidakis, Caitlin M. Gillis, Delphine Sterlin, David Hardy, Michel Cogné, Lynn E. Macdonald, Andrew Murphy, Naxin Tu
SJR Q1Nature CommunicationsOA

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BioengineeringChemical Engineering
15
Article|3 citations·2023
Exploring the impact of nucleic acids on protein stability in bacterial cell lysate
Soojeong Ham, Chang‐Han Lee
SJR Q2Biochimica et Biophysica Acta (BBA) - General SubjectsOA

- Addition of salt enhanced thermal stability of model substrate proteins by reducing electrostatic repulsion between protein molecules. - However, the opposite effect was observed with bacterial cell lysate, indicating that certain molecules within the lysate could enhance protein stability via electrostatic interactions. - Such molecules present in cell lysate were found to be nucleic acids known to have a potent anti-aggregation activity toward proteins involving electrostatic interactions. -

EcologyEnvironmental Science

Research Areas

Radiology, Nuclear Medicine and ImagingMolecular BiologyInfectious DiseasesImmunologyBioengineeringInformation Systems

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