The research in my laboratory is to understand how epigenetic events determine stem cell self-renewal and differentiation. The establishment of pluripotency or differentiation of pluripotent inner cell mass or embryonic stem (ES) cells is accompanied with extensive changes to the epigenetic modifications of DNA and histones that regulate DNA access in cell nuclei. Therefore, regulatory factors that control chromatin architecture are potential key proteins for maintaining the pluripotent state or directing differentiation of early embryonic cells into distinct cell types.

Such factors include ATP-dependent chromatin remodeling complexes which hydrolyze ATP to non-covalently restructure, mobilize, or eject nucleosomes in order to modulate transcription factor access to chromosomal DNA. Among the various members of the ATP-dependent chromatin remodeling superfamily is the SWI/SNF subfamily, consisting of two closely related SWI/SNF remodeling complexes BAF and PBAF in mammalian cells. We will define the epigenetic mechanisms mediated by SWI/SNF complexes in the self-renewal and differentiation of ES and cardiac progenitor cells using an integrated strategy combining genetics, cell biology, molecular biology, and biochemistry.

Many serious medical conditions, such as birth defects, are due to defective differentiation of stem cells into various human tissues. Understanding the epigenetic events mediated by ATP-dependent chromatin remodeling in ES and cardiac progenitor cells is crucial for revealing the etiology of related pediatric diseases and may provide clues to develop modern medical treatments such as small molecule drugs, gene or stem cell/progenitor cell therapies against these diseases.

Recent Publications

Wang, Z., Zhai, W., Richardson, J.A., Olson, E.N., Meneses, J.J., Firpo, M.T., Kang, C., Skarnes, W.C., and Tjian, R. Polybromo protein BAF180 functions in mammalian cardiac chamber maturation. 2004; Genes Dev. 18:3106-3116.

Martin-Puig, S., Wang, Z., and Chien, K.R. Lives of a Heart Cell: Tracing the origins of cardiac progenitors. 2008; Cell Stem Cell. 2:320-331.

Gao, X., Tate, P., Hu, P., Tjian, R., Skarnes, W.C., and Wang, Z. ES cell pluripotency and germ layer formation require the SWI/SNF chromatin remodeling component BAF250a. 2008; Proc Natl Acad Sci U S A. 105:6656-6661.

*Yan, Z., *Wang, Z., *Sharova, L., Sharov, A.A., Ling, C., Piao, Y., Aiba, K. , Matoba, R., Wang, W., and Ko, M.S.H. The BAF250b-associated SWI/SNF chromatin-remodeling complex is required for the maintenance of undifferentiated mouse embryonic stem cells. 2008; Stem Cells. 26:1155-1165. *These authors contributed equally to this work.

Huang, X., Gao, X., Trelles, R., Ruiz-Lozano, P., and Wang, Z. Coronary development is regulated by ATP-dependent chromatin remodeling component BAF180. 2008; Dev Biol. 319:258-266