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.
Research Overview
Research Output Trend
Figures are computed from collected data and may differ slightly.
Selected Papers
15The 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
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.
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
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
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
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
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
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
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- 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. -
Research Areas
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