The research areas in our lab are computational genomics and bioinformatics, with a strong focus on mining large-scale high-throughput genomic data. We develop and apply computational techniques for integrating data from comparative genomics, functional genomics and epigenomics to better understand structure, transcription, regulation, and evolution of the human genome, and to investigate how these functions change during developments, diseases and cancers. While we apply similar bioinformatics approaches to the developments of various tissues and organs, we especially focus on genomic functions involved in the development, specification, maturation, and maintenance of human neural system and heart. Our goal is to better understand the genetic base of neuronal and heart development, neuropsychiatric disorders, and other brain diseases. We expect to identify new therapeutic targets such as specific genes whose regulation is disrupted during the early development of patient brains. Applying the same bioinformatics and genomics strategies to mouse models, we also have a strong research program studying the genetic networks and molecular base of cogenital heart diseases, including single cell analysis.
In collaboration with other experimentalist experts, we grow human neurons in dish by induced pluripotent stem cell (iPSC) technology in order to model human neuronal development and differentiation. We begin by developing iPSC lines from both patients and matching controls, differentiate them to neurons, then use RNA-seq and other deep sequencing technology to identify differentially regulate genes by comparing the transcriptomes between patient-derived neurons and controls. By using advanced experimental technology and computational methods like iPSC technology, deep sequencing (e.g, RNA-seq, scRNA-seq and ChIP-seq), and systems biology approaches for our research, we have identified many novel long non-coding RNA genes that are involved in embryonic neurogenesis and potentially neuropsychiatric disorders. We also find that many genes show allele-biased gene expression in different brain regions, including some that have been implicated in Schizophrenia and Autism Spectrum Disorders, which may help explain some aspects of parent-of-origin effects, twin discordance and reduced penetrance.