종양후생유전학연구실

The recent discovery of TET (Ten-eleven-translocation) enzyme functions has led to a paradigm shift in our understanding of how imbalances in DNA methylation-demethylation dynamics are coupled to cancers. The TET proteins (TET1, TET2 and TET3) alter DNA methylation status by sequentially oxidizing 5-methylcytosine. The resulting oxidized methylcytosines function as intermediates in DNA demethylation as well as independent epigenetic marks. Because DNA methylation and hydroxymethylation are highly aberrant in cancers, leading to abnormal gene expression and genomic instability, we will take the DNA methylation-demethylation cycles as a starting point of our research, with an emphasis on understanding the role of TET proteins in normal and oncogenic hematopoiesis. Global epigenomic alterations common in cancers represent an attractive target for cancer therapy because epigenetic marks are generated and erased in a highly dynamic and reversible manner. Loss of TET function is generally associated with malignant transformation. Thus, we are exploring whether manipulation of methylcytosine oxidation status by targeting TET enzymes displays clinical efficacy in cancer patients. To this aim, we will identify proteins or small molecules that physically or functionally interact with TET enzymes, then molecular basis of their action and therapeutic effects will be rigorously tested alone or in combination with conventional therapy. The intricate interplay between genetic and epigenetic pathways assumes pivotal roles in governing both normal and malignant cellular development and function. Then, how do alterations in the epigenetic landscape disturb the barrier between normal and malignant states, ultimately leading to the development of diseases such as cancers? How can we transl