Technological advances have provided opportunities that allow genetic variants in the whole genome to be analyzed in association studies, thus giving unique opportunity for identifying moderate risk alleles without prior knowledge of etiology. This genome-wide association studies (GWAS) have been successful in identifying the genetic component of predisposition to many human complex diseases. By applying novel and precise analytical methods, current research focuses on exploring the biological mechanisms underlying susceptibility loci known as causal variants. In three of our recent studies, based on the data of GWASs, we have demonstrated the molecular basis of important causal variants associated with breast cancer progression and hyperlipidemia with an emphasis on using post-GWAS analysis and experiments to gain insight into etiology. A series of experimental approaches, including the use of bioinformatic databases (such as eQTL and ENCODE), cell-based analyses and CRISPR/Cas9 genome-editing system, were used and identified specific transcription factors, which were able to discriminately bind to the specific alleles of these genetic variants. These studies demonstrate how post-GWAS studies can be conducted to generate useful information of translation relevance.
Our lab is also interested in breast cancer stem cell. We have identified specific marker, which is a long-non-coding RNA, that can be specifically identified estrogen-receptor-positive breast cancer stem cell. In addition, we have highlighted a microRNA-mediated suppression of CXCR4/p-Akt signaling and thereby affected mesenchymal stem-cell genesis, indicating its potential as a therapeutic target for invasive breast cancer.
Finally, we have introduced new approaches to explore possible contribution of histone overexpression, histone modification and DNA repair affecting breast cancer progression.