Cellular heterogeneity within a tumor plays an important role in tumor progression and drug resistance by driving phenotypic diversity. Tumor-initiating cells have been implicated as one of the determining factors that contribute to intratumor heterogeneity. Thus, a key to successful cancer therapy is to identify the critical nodes in the oncogenic network that shapes cellular heterogeneity and alters malignant potential of tumor-initiating cells and to target them to reverse cancer phenotypes.
Our research has been focusing on identification and characterization of epigenetic factors for targeted cancer therapy. A series of our recent findings have demonstrated an essential role of a protein arginine methyltransferase and a transcriptional coactivator/phosphatase in the maintenance, chemoresistance, and tumorigenesis of neuroblastoma tumor-initiating cells.
We have also initiated exploring the therapeutic potential of small molecule compounds that selectively disrupt the activity of this regulatory axis. We are leveraging various technologies to understand the molecular mechanisms underlying the oncogenicity of this protein complex. By utilizing multiple model systems, we propose to identify key molecular targets that are critical to a relevant biological phenotype and to develop novel strategies for effective cancer therapy.