RESEARCH KEYWORDS
1. Extracellular vesicles (EVs; e.g., exosomes, microvesicles)
2. DNA repairs & gene therapy
3. Molecular bioimaging
4. Pharmacokinetics
We create and apply new technologies to explore biological phenomena!
Always learning, always exploring.
Research Theme I
Molecular Bioimaging & Extracellular Vesicles
Extracellular vesicles (EVs) are lipid bilayer–enclosed nanoparticles spanning a wide size range, from ~30 nm exosomes to microvesicles that can exceed several micrometers in diameter. In contrast, bionanoparticles such as exomeres and supermeres are typically <50 nm and lack a surrounding membrane. Both EVs and these non-membranous particles transport bioactive molecules—including lipids, nucleic acids, and proteins—thereby shaping fundamental biological processes and contributing to disease pathogenesis, most notably in cancer. The Lai Lab is advancing next-generation EV imaging technologies aimed at mapping vesicle networks with high spatiotemporal resolution while simultaneously enabling integrated molecular analyses.
Multi-resolution imaging and biodistribution analysis of EVs. PalmGRET, a bioluminescence resonance energy transfer-based reporter, was developed to allow pan-bionanoparticle labeling and multi-resolution imaging of EVs in vivo and in vitro. (Wu et al., Advanced Science, 2020)
Live-cell confocal microscopy of EV exchange between multiple cell populations. 293T cells stably expressing either PalmGRET (293T-PalmGRET) or PalmtdTomato (293T-PalmtdTomato) were co-cultured and imaged under confocal microscopy to visualized released EVs. (Wu et al., Advanced Science, 2020)
Super-resolution, live-cell imaging of 293T-PalmGRET ad EVs. 293T-PalmGRET cells and released EVs were imaged under epifluorescence microscope or super-resolution fluctuation radial fluctuation nanoscopy (SRRF). (Wu et al., Advanced Science, 2020)
In vivo imaging of intravenously administered EVs. EVs derived from liver cancer HCA1 cells stably expressing PalmGRET were administered via the tail vein, and visualized under in vivo imaging system (IVIS). (Wu et al., Advanced Science, 2020)
Biodistribution analysis of liver cancer-derived EVs. Liver cancer HCA1 released EVs showed a robust lung and liver tropism. (Wu et al., Advanced Science, 2020)
Research Theme II
DNA Repairs & Gene Therapy
The Lai Lab is developing tools to watch how cells repair DNA damage — a process essential for protecting us from cancer and aging. Every day, our DNA suffers trillions of small errors that must be fixed to keep genomes stable. To study this, the team created the Bioluminescent DNA Repair Reporter (BLRR), a system that uses light signals to track DNA repair in real time, without invasive methods. This breakthrough could reveal why patients respond differently to treatments like chemotherapy or CRISPR and help guide safer, more effective therapies.
A multiplexed bioluminescent DNA repair reporter (BLRR) enables sensitive and non-invasive monitoring of double-strand break (DSB) repair dynamics both in vitro and in vivo. In BLRR cells, DSBs can be repaired by two major pathways: non-homologous end joining (NHEJ) or homology-directed repair (HDR). The BLRR system can serve as a high-throughput screening platform for identifying compounds that modulate DSB repair. It can also be applied to evaluate repair dynamics across diverse cell types, including cancer cells. Furthermore, the BLRR is a versatile tool for studying and optimizing genome-editing technologies, such as novel Cas proteins, guide RNAs, and improved delivery strategies. (Chien et al., Nucleic Acids Research, 2020; Nature Protocols, 2021)
Institute of Atomic and Molecular Sciences, Academia Sinica
No. 1, Roosevelt Rd., Sec. 4, Taipei, 106319, Taiwan