Research Focus

(See an interview of Dr. Zhao about our lab research:)

The research in our laboratory focuses on understanding the molecular mechanisms that regulate neural stem cells and neuronal development, with the goal of developing better treatment for neurodevelopmental and neurological
disorders.

We use transgenic mice, human and rodent neural stem cells (NSC), and human pluripotent stem cells (iPSC, ESC), as well as CRISPR gene-edited stem cells as model systems. We employ a combination of cutting edge methods in genetics, genomics, proteomics, imaging, and behavior to interrogate the roles of genes, epigenetic regulators, RNAs, and proteins in neuronal development and their implications in neurodevelopmental disorders. Our projects are continuously evolving with our current research effort directed towards several central questions:

 

1. We investigate the functions of specific genes and epigenetic regulators in neuronal development and how theirmutations lead to neurodevelopmental disorder.Epigenetic mechanisms, acting through DNA methylation and chromatin remodeling, have profound regulatory roles in mammalian gene expression. We have been studying how mutations in epigenetic regulators MeCP2 and MBD1 lead to altered gene expression and impaired neuronal development in the context of Rett syndrome and autism. Post-transcriptional gene regulations are mediated by complex mechanisms,
including noncoding RNAs such as microRNAs (e.g. miR-137, miR-184) and RNA-binding proteins (e.g. FMRP, FXR1P, FXR2P). One major area of our study is
to investigate the function of FMRP in neuronal development and pathogenesis of
fragile X syndrome.  

 

2. We interrogate the complex relationships between gene expression, neuronal plasticity, neural circuit, and behavior.

Identification of the gene regulatory networks in responses to environmental signals, comparison among these gene networks, and construction of predictive models of global circuit behavior from these networks are among the biggest questions of modern neuroscience. We hypothesize that the genetic or epigenetic mediators of Gene X Environment interaction are likely cell type-specific and brain circuit-specific.  Together with my collaborators, we use cutting edge single cell and cell type specific genetics, imaging, and network modeling methods to achieve our goals.