Y I L A B O R A T O R Y
We learn and grow together
Our main research interest is understanding
the molecular mechanisms behind extrachromosomal DNA (ecDNA) behaviors in cancers
EcDNAs (labeled with two-color probes) in a patient-derived glioblastoma neurosphere cell
EcDNA frequency across primary cancers
EcDNA, a DNA circle found outside the chromosomes, often contains major oncogenes and regulatory elements. This oncogenic circular DNA is frequently amplified in solid cancer derived from multiple organs, including the brain, breast, gastric, etc. While the clinical importance of ecDNA has been demonstrated for the past few years, the behavior and biological roles of ecDNA need to be clarified.
Eunhee’s previous research focused on establishing a live-cell ecDNA tracking method (aka ecTag) and revealed that ecDNA creates multiple layers of intratumoral heterogeneity:
1) Acentromeric ecDNAs are unevenly segregated to daughter cells during cancer cell division. And this creates intratumoral heterogeneity at the genomic level within a few cell cycles.
2) ecDNA molecules tend to create hubs where transcriptional machinery is recruited, and oncogenes on the ecDNA get transcribed much higher. Thus, ecDNA can create another layer of intratumoral heterogeneity at the transcriptional level via ecDNA hub formation.
To learn more about the live-cell ecDNA tracking method, visit the ecTag website!
Along with this discovery, recent efforts from ecDNA researchers have collected many fascinating phenomena related to ecDNA in cancer progression, such as its role as a mobile super-enhancer, its contribution to drug resistance, etc. [More stories about ecDNA].
Although the improved understanding of ecDNA with a significant growth of research tools and models, the molecular mechanisms that control ecDNA’s behaviors have not been discovered.
Yi Laboratory will put our effort into making a clear answer to these specific questions:
Stress Resistance
1) How do ecDNA-harboring cancer cells outcompete other cells with different focal amplification modes (linear amplification, often referred to as a homogeneously staining region, HSR.) under different cellular stresses?
Drug Resistance
2) How do ecDNAs integrate into the chromosome and facilitate cancer cell survival upon drug treatment?
Tumor Microenvironment
3) How do ecDNA-harboring cancer cells communicate with neighboring cells such as ecDNA-free cancer cells, immune cells, and other stromal cells?
We will leverage cutting-edge technologies (Live-cell imaging, High-throughput genetic screening, etc.) and fundamental molecular and cell biology lab techniques.