Research

Exploring the Wonder of Life Sciences with Nanotechnology

Research

Visual Antibody-omics from a Blood Drop

We are developing a visual antibody-omics platform for direct, real-time visualization of the polyclonal antibody landscape. Using negative-stain electron microscopy (nsEM), we capture snapshots of antibody responses following vaccination or infection, generating semi-quantitative maps of epitopic diversity against defined immunogens. In SARS-CoV-2 studies, this approach reveals how antibodies targeting conformational non-RBD regions drive broad cross-neutralization across variants, while in influenza HA research, it uncovers how cross-reactive antibodies to conserved HA epitopes are shaped by pre-existing exposure. We are currently refining sample-preparation workflows and developing antibody subtype–specific analyses, advancing toward a more comprehensive and visual understanding of humoral immunity.

Mechanistic Insights into Antibody Multivalent Binding

Traditional structural studies have focused on single-Fab footprints to explain antibody potency, breadth, and mechanisms of neutralization. Yet in vivo, antibodies act as full, IgG molecules—bivalent by design, gaining not only epitope-mapping capacity from each Fab arm but also greater avidity and enhanced neutralization through multivalent binding. Understanding this multivalency is essential to uncovering how antibodies truly operate at the viral surface. We combine molecular-dynamics simulations, functional neutralization and binding assays, and cryo-EM to reveal how IgG multivalency—via antigen clustering and higher-order binding geometry—empowers even low-affinity antibodies to achieve potent neutralization and drives variant-specific differences in antibody efficacy. To further dissect this spatial dimension, we are developing DNA-based nanostructure “scaffolds” that precisely control antigen spacing at the nanoscale, offering a unique platform to probe how antigen organization governs antibody engagement and viral neutralization.

DNA Matrix as a Universal Platform for Subunit Vaccines

The DNA Matrix is a dynamic supramolecular adjuvant assembled from five short, unmodified DNA strands. Its right-handed colloidal architecture prolongs antigen retention and enhances lymphatic transport, thereby eliciting strong antibody responses through the TLR9–MyD88 pathway. This safe and multifunctional platform provides potent protection against both viral and bacterial infections, offering a promising strategy for next-generation vaccine design. We are currently optimizing DNA hydrogel sequences to understand how material properties influence immune activation, employing near-infrared (NIR) imaging to systematically evaluate the in vivo behavior of hydrogels with different sequence motifs (e.g., CpG vs. non-CpG) and physical characteristics (e.g., gel strength). These studies aim to elucidate the intrinsic link between antigen dynamics and carrier behavior, ultimately guiding the rational design of DNA hydrogel-based vaccines with enhanced immunogenicity and controlled antigen delivery.

DNA Nanotags for Multiplex EM-Based Imaging

We are developing DNA nanostructure–based nanotags as versatile tools for electron microscopy (EM) imaging. Owing to their precise programmability, defined geometries, biomolecular conjugation capacity, and compatibility with cryogenic sample preparation, these nanotags hold great promise for multiplexed EM visualization of complex biological systems. In parallel, we are designing DNA origami scaffolds integrated with site-specific incorporation of unnatural amino acids (UAA) to precisely define the orientation and spatial arrangement of antigen display. This programmable approach enables systematic investigation of multivalent antigen–antibody interactions and provides structural insights into viral assemblies such as dengue and HIV.