Jun Yang Lab

In our work on histone modifiers, we explore the possibility that the modifiers work in conjunction with oncogenic transcription factors to drive tumorigenesis. We focus on epigenetic modifiers with an eye toward finding an alternative way to block tumorigenesis. Our lab has found that the histone lysine demethylases controls the “undruggable” MYC and PAX3-FOXO1 expression—a finding that holds promise for targeting these oncoproteins in treatment. 

In collaboration with the Department of Chemical Biology and Therapeutics, we now develop small molecules to target lysine demethylases in neuroblastoma and rhabdomyosarcoma. Our preclinical model using patient-derived xenografts and cell lines has shown promising results that we hope to bring to clinical trial.

Our disease modeling work focuses on the MYC oncogene in solid tumors, such as neuroblastoma and hepatoblastoma, and how these diseases initiate, progress, and metastasize. Understanding these factors and mapping the oncogenic pathways in models may allow for the future development of novel treatments and therapeutic targets. As an example, we employed genome-wide CRISPR screening and discovered multiple novel genetic modifiers that may synergize or antagonize the effect of the chemotherapeutic agent doxorubicin. Based on those results, we developed a combination therapy that shows to be more effective than doxorubicin alone in cell line, patient-derived xenografts and transgenic models. Exploiting newly established transgenic cell lines, we are now extending our research in this area to identify new therapeutic agents by high-throughput drug screening. 

In our work, our laboratory hopes to advance the understanding of how genetic abnormalities couple with epigenetic alterations in tumorigenesis and disease progression. Advancements in these foundational aspects will help develop precise treatments for children with high-risk solid tumors.