My research focuses on leveraging integrative omics and patient derived model to develop precision therapy for rare pediatric glioma. I seek to optimize the application of next generation omics to tailor novel therapeutic strategy in the context of drug discovery and drug development for rare pediatric glioma patients. The heterogenous nature of pediatric glioma tumors, even in the same subtype, combined with the lack of known mechanism and actionable target called for more study to tailor therapeutic strategy for each glioma subtype or even each patient. In addition, the plethora of next generation omics enable us to choose the right tools to dissect molecular mechanism at different cellular level including genomic, transcriptomic, proteomic, and beyond. As an example, my project started with a patient who was diagnosed with anaplastic pleomorphic xanthoastrocytoma (APXA), a rare pediatric glioma with WHO grade III. To study about this disease, we developed patient derived xenograft and xenoline from donated tumor tissue of this patient. We then characterized our model with DNA-seq, RNA-seq and proteomic sequencing. We identified MAPK pathway as potential target and tested several different strategies of targeting MAPK including vertical combination and horizontal combination therapy. Therapeutic efficacy was evaluated by integrative omics at the transcriptomic, proteomic, and post translational modification level. Since this model harbor distinct molecular signature, a CDC42SE2-BRAF gene fusion and CDKN2A/B loss, we then question whether our strategy for this model can be adopted in APXA patient who harbor different type of BRAF genomic landscape, BRAFV600E and BRAF-WT. Further we want to answer whether precision medicine is required for each patient of APXA due to their molecular heterogeneity, or precision therapy can be applied in sub-group of this disease by using BRAF as stratification marker. For our long term goal, we want to expand our research to other rare high grade pediatric glioma which currently do not have standard management therapy.
Post-doctoral Fellowship - Indiana University School of Medicine, Indianapolis, IN 2021
Ph.D. - Purdue University, West Lafayette, IN 2016