Research focus
A ~2 meter-long linear genome is folded and entangled to fit in a tiny size of an individual nucleus. The 3-dimensional structure of the genome is formed during the compaction process.
a.k.a. 3D genome folding
The 3D genome folding, mediated by the structural proteins (e.g., CTCF, cohesin) and complex epigenetic networks, is involved in transcription regulation of the genes that determine the key characteristics of the cells.
The technical advancement of molecular technology combined with next-generation sequencing has enabled the unraveling of the detailed structures of 3D genome folding onto 2-dimensional heatmaps (example below).
3D genome folding is involved in critical mechanisms of disease development (e.g. leukemia, medulloblastoma, schizophrenia, fragile X syndrome, immune responses, metabolic changes, etc) and key biological phenomena (e.g. cell development).
Our lab focuses on
1) investigate how 3D genome folding affects disease development and what epigenetic and cell biological mechanisms are dynamically involved, and
2) develop technologies to engineer 3D genome folding and manipulate its function to the target gene expression and, ultimately, the cell identity.
Some of the currently active running projects are as follows:
Project 1 : Unstable genome structures in cancer and its implication in 3D genome
Environments (e.g., infection, nuclear instability, etc) affect somatic variations of the genome structures (e.g., SNPs, CNV, SV, etc.) that are among the leading causes of cancers. Although those genomic variations are directly connected to the changes in 3D genome networks and epigenetic landscapes, their driving molecular mechanisms have not been fully understood. To answer this question, we create the 3D genome folding maps of the cancer samples with unstable genome structures and investigate their key mechanisms and clinical implications.
Project 2 : Dynamics and functions of the genome during immune responses
The immune system is critical to the defense of our body from lots of diseases, from external infections to internal disease cells. For effective immune responses, the immune cells differentiate into numerous types of cells with distinct functions. Although the structural changes during the differentiation have been extensively reported, the mechanisms behind these changes and their functions have not been well understood. We identify the critical changes in the genome structures during the differentiation and investigate their unknown mechanisms and potential targets to reprogram the immune cells.
Project 3 : Engineering 3D genome folding
3D genome is highly organized in a hierarchical order : from loop, TAD, compartment, and chromosome. The loop extrusion model has been widely accepted to explain how loops are formed (see below left video). Still, its cause-effect mechanism between loops, transcription, and other epigenetic features has not been fully understood. Moreover, the forming mechanisms of the domain structures of the 3D genome are still elusive. Our lab is developing a new technology capable of reshaping the 3D genome folding domains and investigating its functions to target genes.
