2.1 Invent epigenomic editing tools will be based on Argonaute (AGO) 1-4:RNA complex.
2.2 To use the epigenomic editing tool to study to study the biological roles of epigenetic modification of repetitive sequences, including Alu, LINE-1 and ononucleotide A repeats. Moreover, this epigenetic editing will be epigenetic therapy models for cancer, SLE and aging by reversing Alu or LINE-1 hypomethylation by AGO4-Alu or LINE-1 RNA.
2.3 We will combine computational biology and genetic engineering techniques to test if engineered AGO:RNA complex can regulate gene expression.
2.4 To study genomic instability, we will combine AGO4-Alu RNA with HMGB1 to evaluate the role of phy-RIND-EDSBs in preventing genomic instability in cancer and in aging process.
2.5 To invent 2.5 to invent highly sensitive and effective cancer screening approaches based on
2.5.1 Epigenetic and protein alteration in WBC due paracrine action of cancer.
2.5.2 Epithelial and tissue specific DNA methylation in circulation.