Current Research
In recent years, the Ahn lab has focused on the following areas: the detection of low-frequency mutations on a genome-wide level using a novel deep sequencing technology termed Duplex Sequencing (DS); and the regulation of cell function by microenvironments such as extracellular matrix (ECM)-biomimetic nanotopography. We have applied these cutting-edge experimental approaches to study genomic changes and migratory phenotypes of breast cancer and glioblastoma. The ultimate goals of the Ahn lab’s current and future research projects are to identify biomarkers for the early detection of therapy resistance and tumor recurrence using cutting-edge deep sequencing and ECM-biomimetics technologies, and to develop a novel strategy for preclinical screening of anti-migratory chemotherapeutic agents.
Ongoing Projects
Mutagenesis and migration in glioblastoma cells
Glioblastoma, the most aggressive brain cancer, invariably reoccurs after surgery and rapidly develops resistance to radiation therapy and chemotherapy. The invasive nature of glioblastoma is a major cause of therapeutic failure. Furthermore, the study of glioblastoma invasion is particularly challenging due to the lack of good experimental models that recapitulate the tumor microenvironment.
For genetic characterization of tumors, most studies have investigated clonal (high-frequency) mutations and have not analyzed sub-clonal (low-frequency) mutations due to the high error rates (10-1 to 10-3) of DNA sequencing methods. Therefore, little is known about genetic variations and heterogeneities that can determine the evolution of invasive and therapy-resistant subpopulations of glioblastoma cells.
To recapitulate in vivo 3D tumor microenvironments, we have applied nanotopographically defined extracellular matrix (ECM)-mimetic culture platforms. To accurately detect subclonal mutations as well as clonal mutations, we have employed Duplex Sequencing (10-8 to 5×10-8), which is >10,000-fold more accurate than other high-throughput sequencing methods.
Genome-wide profiling of mutations in glioblastoma (GBM)
To maximize the scope and impact of this relatively large project, we collaborate with multiple laboratories (Drs. Lawrence A. Loeb, Ray Monnat, Tom Walsh, and Suleyman Gulsuner at the University of Washington and Dr. Charles Cobbs at Swedish Neuroscience Institute).
Genomic variations during transformation of breast stem cells into tumorigenic cells
Genome sequencing studies have investigated high-frequency (clonal) mutations and have not explored low-frequency (subclonal and rare) mutations due to high error rates of conventional sequencing methods. We perform a comprehensive mutation analysis of the whole exome and the selected genes in a human breast stem cell-derived carcinogenesis model.
Other Emerging Projects
- Defining the transcriptomic basis for glioblastoma cell invasiveness
- Changes of mitochondrial subclonal mutations and mitochondrial protein expressions in breast normal cell senescence
Recently Completed Projects
- Regulation of breast cancer stem cell migration by nanotopographical cues
- Mutational characterization of the whole mitochondrial genome in immortalization of different breast epithelial cell types
- Detection of low-frequency mutations and identification of heat-induced artifactual mutations
- Ultra-accurate genome-wide analysis of mitochondrial DNA mutations during breast stem cells into tumorigenic cells
- Detection of ultra-rare mitochondrial mutations in breast stem cells
- Regulation of sphingosine-induced apoptosis by MYCN in PAX3-FOXO1-positive alveolar rhabdomyosarcoma
- The expression changes of DNA-repair related genes during breast stem cell tumorigenesis
