Single-cell Epigenetics
Epigenetic alterations caused by interaction between transcription factors (TFs) and chromatin regulators control cell state transitions by activating or suppressing specific sets of genes. We defined the cell states in rhabdomyosarcoma, and other solid tumors, with the cell state transition dynamics unsolved. We propose that a perturbation of gene regulatory elements, or specific TFs or chromatin regulators, could direct cells towards a specific cell state.
Fusion oncogenes in pediatric solid tumors
A handful of fusion oncogenes were well studied in leukemia, Ewing sarcoma, and rhabdomyosarcomas. Yet thousands of fusion genes have been discovered across pediatric solid tumors, though less frequent, but always associated with a worse prognosis in patients. Family members who have had kids die of rare tumors that bear these fusions are desperate to know more. Yet, such research is rarely funded. We hope to first generate a list of putative fusions, then model these fusion genes in lab models, and finally understand the mechanism of it by comprehensive profiling.
Modeling of rare tumors
Contingent to the second research topic, any other type of oncogene could be introduced simultaneously. We will employ transgenic zebrafish, mouse models, or in vitro stem cell culture to model such rare tumors for detailed mechanism studies. Then patient-derived samples, either frozen or formalin-fixed paraffin-embedded, or primary cell culture, patient-derived xenograft, or even organoids to validate our bench findings. This ensures the translational value of our hard work on bench.
