Zhexing Wen, PhD
Office: Department of Psychiatry and Behavioral Sciences
447 Whitehead Rsch Bldg
Atlanta, GA 30322
The research of our laboratory centers on understanding the basic molecular mechanisms underlying psychiatric disorders. Severe psychiatric illnesses, such as schizophrenia, major depression and autism spectrum disorder, are chronic and complex neurological diseases that affect a large portion of the world's population and have devastating consequence for the sufferers, their families and for the society as a whole. However, the causes of these mental disorders are still poorly understood, and the currently available treatments are very limited and only partially effective. A deeper understanding of the underlying disease biology is essential to improve diagnoses and therapies. Induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells of healthy subjects and patients which capture identical risk alleles as the donor individual and provide a renewable source of previously inaccessible, disease-relevant human cell types, offer an unprecedented opportunity to recapitulate both normal and pathologic human development, thereby enabling a new approach for understanding human disease mechanisms and for drug discovery with higher predictability of their effects in humans. By establishing in vitro 2-D and 3-D cellular models with patient-specific iPSCs, our primary research interest is to understand the pathogenesis of psychiatric disorders at the molecular, cellular and circuitry levels, and to translate such knowledge into therapeutic targets for developing novel treatment strategies.
Three major research areas are being pursued in our lab:
- To understand the biological functions of risk genes in psychiatric disorders, and to identify pathological processes that may contribute to the pathogenesis of these complex diseases by differentiating human iPSCs into disease-relevant cell types such as cortical glutamatergic neurons, GABAergic neurons, and astrocytes.
- To identify the core signature of psychiatric disorders and potential therapeutic targets by systematically comparisons of gene/protein expression profiles and cellular phenotypes from cohorts of patients with different genetic origins.
- To establish novel screening platforms using human iPSC-derived specific cell types such as neurons and astrocytes for drug development based on understanding of the relevant disease mechanisms.
To achieve these goals, our research employs a combination of cutting edge technologies, including human non-integrated iPSCs generation, genome editing, specific cell type differentiation, brain-region-specific 3-D organoids generation, as well as molecular biology, biochemistry, molecular/cellular imaging, electrophysiology, deep sequencing and bioinformatics, and high-throughput screening. It is our hope that our studies will bring novel mechanistic insight into these disorders and provide new therapeutic strategies for these devastating diseases that affect millions of people worldwide.
- View publications on Pubmed