Our laboratory is interested in understanding how the nuclear lamina regulates cellular functions in development, homeostasis and aging. Lamins are the major structural components of the nuclear lamina that is associated with chromatin in the nucleus and connected to the cytoskeleton via nuclear membrane proteins. Since genetic mutations of lamins cause a list of human diseases such as premature aging, muscular dystrophy, and lipodystrophy, the study of lamins has taken a central stage not only in basic cell biology but also in clinical applications. Furthermore, recent studies show that physiological alteration of the nuclear lamina is involved in the development of age-associated tissue degeneration and metabolic disorders. Our research projects involve a wide range of experimental approaches, including genetics in model organisms, cell culture, biochemistry, and genomics.

Characterization of lamin-associated tissue dysfunctions

We have established various lamin knock out (KO) mice and mouse embryonic stem cells (mESC), including lamin-B1, -B2 and -A triple KO mESCs. Using various KO mouse and cell culture models, we are currently exploring the precise role of lamins in tissue functions and their implication in human diseases. We are also interested in examining the role of lamins in normal aging and development of metabolic disorders.

The mechanisms in which lamins regulate gene expression

Gene expression model is an attractive hypothesis to explain lamin-mediated tissue dysfunctions, which proposes that alteration of lamin expression or lamina structure causes changes in 3D genome organization and gene expression. We have shown the fundamental role of lamins in 3D genome organization using lamin TKO mESCs. Based on the principal acquired from mESCs, we will focus on elucidating the mechanism in which lamins regulate chromatin interactions and gene expression upon aging and metabolic imbalances.

Improvement of Hi-C technique and its application

Chromosome conformation capture (3C) technique and its derivatives such as Hi-C have provided high resolution 3D chromatin interaction maps and insights on genome organization and its function in gene expression. However, Hi-C analysis and other 3C-based techniques are limited to in vitro cultured cell lines mainly due to their requirements for massive amounts of samples. We are developing an efficient Hi-C technique that enables to map small number of cells, which might allow mapping 3D chromatin interactions from rare in vivo cell types.