Professor, Department of Cell Biology
Ullmann Bldg., Room 903
HUMAN EMBRYONIC STEM CELLS, EPIGENETICS AND REPROGRAMMING
Epigenetic is the study of mitotically or meiotically heritable changes in gene function not associated with changes in DNA sequence. Epigenetic regulations are mediated by changes in chromatin structure that alter access of transcription factors to their cognate binding sites, and therefore, expression levels of genes and transgenes. Understanding these regulations is critical for gene therapy, cancer therapy and generally to gain a greater ability to modify mammalian genomes. The main focus of my lab is to understand the molecular bases of some of these epigenetic regulations. We are particularly interested in using massively parallel sequencing technologies to understand the mechanisms of establishment, maintenance, and inheritance of chromatin structures. We have recently developed a method termed TimEX to determine the timing of DNA replication genome-wide. We are using TimEX in conjunction with Chip-Seq and RNA-seq to study epigenome organization.
The second major focus of the lab is to use the epigenetic information obtained above to improve the reprogramming of somatic cells into induced pluripotent stem cells and to develop methods to reprogram somatic cells into other stem or progenitor cells by over-expression of transcription factors without reverting to an embryonic state.
Finally, we are currently developing a system to produce normal human red blood cells with embryonic, fetal or adult characteristics by forced differentiation of human ES cells using a genetic approach. The goal is to generate large amount of genetically homogenous, genetically modifiable normal erythroid cells at different stages of differentiation. This system could allow us to produce red cells for transfusion medicine, to study the silencing of the gamma-globin gene, to develop silencing resistant gene therapy cassettes that will be useful to cure the hemoglobinopathies, and to generally study the establishment and maintenance of epigenetic signals directly in untransformed human cells. We also have active research projects on the role of DNA methylation, DNA replication, histone modification, linker histones, and transcriptional interferences in the determination of expression levels.