Assistant Professor of Genetics
200 Longwood Ave
Warren Alpert 149G
Boston, MA 02115
Lab Size: Between 10-15
The genomes of eukaryotic cells are organized by chromatin. Chromatin is subject to a variety of covalent modifications in both histones and DNA. These covalent modifications play essential roles in regulate chromatin structures and consequently impact chromatin functions, include transcription, development, cell fate reprogramming and differentiation. Deregulation of chromatin modifications contribute to the development of various diseases including neurological diseases and cancers. Our long-term goal is to apply what we have learned in basic research to the study of human diseases.
Over the past decade, the Zhang lab has identified and characterized several classes of chromatin modifying enzymes that include (1) the ATP-dependent nucleosome-remodeling and histone deacetylase complex NuRD; (2) histone methyltransferases (eg. EZH2 and hDOT1L); (3) the JmjC-family histone demethylases; (4) histone H2A ubiquitin E3 ligase PRC1; and (5) the Ten Eleven Translocation (Tet) family of 5-methylcytosine dioxygenases. Build upon the success of biochemical approaches, the lab has also developed the capabilities of mouse genetics, high-throughput genomics and epigenomics, single-cell transcriptomics, DNA methylome, CRISPR-based screen and imaging, etc. The lab is currently focused on understanding the mechanism of preimplantation development, somatic cell nuclear transfer reprogramming, reward-related learning and memory, and cancer development, with a particular emphasis on the role of dynamic chromatin modifications in the above processes.
Lu, F., Liu, Y., Inoue, A., Suzuki, T., Zhao, K., and Zhang, Y. (2016). Establishing chromatin regulatory landscape during mouse preimplantation development. Cell 165, 1375-1388.
Chung, Y.G., Matoba, S., Liu, Y., Eum, J.H., Lu, F., Jiang, W., Lee, J.E., Sepilian, V., Cha, K.Y., Lee, D.R., and Zhang, Y. (2015). Histone demethylase expression enhances human somatic cell nuclear transfer efficiency and promotes derivation of pluripotent stem cells. Cell Stem Cell 17, 758-766.
Wu, H., Wu, X., Shen, L., and Zhang, Y. (2014). Single-base resolution analysis of active DNA demethylation using methylase-assisted bisulfite sequencing. Nature Biotech. 32, 1231-40.
Matoba, S., Liu, Y., Lu, F., Iwabuchi, K.A., Shen, L., Inoue, A., and Zhang, Y. (2014). Embryonic development following somatic cell nuclear transfer impeded by persisting histone methylation. Cell 159, 884-895.
Inoue, A., and Zhang, Y. (2014). Nucleosome assembly is required for nuclear pore complex assembly in mouse zygotes. Nature SMB 21, 609-16.