Our research focus is the epigenetic mechanisms of X chromosome regulation. Mammalian females have two X chromosomes and males have only one X and a gene-poor Y. The phenotypic effects of chromosomal imbalance in mammals are deleterious and haplo-insufficiency for a whole chromosome is not tolerated. Thus dosage compensation has evolved to restore equal expression between the X and autosomes by doubling X-linked gene expression (X up-regulation) and between the sexes by silencing one X in females (X inactivation). We are investigating how mammalian X-linked genes are up-regulated at transcriptional and posttranscriptional levels and how abnormal copy number changes of dosage sensitive X-linked genes attribute to abnormal phenotypes observed in diseases such as X aneuploidy disorders and cancer. To study X-linked gene dosage regulation and effects during early development and in the specific cell lineages such as neuronal cell and cardiomyocytes, we mainly use mouse and human stem cells (embryonic stem cells or induced pluripotent stem cells) and in vitro differentiation for functional analyses including global analyses of gene expression, histone modifications, protein binding and chromatin conformation.