One of the major goals of our lab is to understand the principles and mechanisms of genome organization. The mammalian genome is spatially organized in the nucleus to enable cell type-specific gene expression. Investigating how chromatin organization determines this specificity remains a big challenge due to the high-scale complexity of the genome: various kinds of chromatin regulators, different types of functional DNA elements, and sophisticated interactions between the two. We are developing high-throughput approaches – both experimental and computational – to discover functional DNA elements and novel genome regulators. Coupling with traditional genomic, molecular, and biochemical approaches, we aim to understand the fundamental principles and molecular mechanisms of genome organization across the tree of life. We further investigate how genome regulation goes awry in diseases, and how we can manipulate, restore, and de novo synthesize chromatin organization to develop new therapeutics.

Some immediate questions/projects that we are working on:

• What factors define TAD boundaries in the genome? CTCF protein itself is NOT sufficient.

• How to categorize chromatin interaction types, and what factors can define them?

• What is a more fundamental and conserved mechanism in shaping 3D genome organization, even in species where CTCF are not conserved?

• How to design and synthesize a new TAD structure? Can we evolve new principles of chromatin organization beyond nature?