Dong-Xin Liu

I received a PhD degree in Cell Biology at 2011. Since then, I kept doing research in Dr. Yu-Hua Chen's laboratory at China Medical University, China. The research is mainly focused on the pathogenesis of neonatal bacterial meningitis. We identified Caspr1 expressed in the brain endothelium, as a novel host receptor for E. coli virulence factor IbeA to facilitate BBB penetration. Blocking IbeA-Caspr1 interaction effectively prevented E. coli penetration into the brain during experimental meningitis (Nat Commun. 2018). In 2019, I as a research fellow, came to Dr. Chung lab at New York Medical College to study the mechanism of schizophrenia (SCZ), utilizing homogeneous populations of developing cortical interneurons (cINs) and glutamatergic neurons derived from healthy control vs SCZ iPSCs. We identified SCZ risk loci genes that are differentially expressed (DE) genes in developing SCZ cINs and found that they converge on the PKC pathway. Knockout of these genes results in PKC hyperactivity in developing cINs, leading to arborization deficits and compromised inhibitory synapse formation. We also identified SCZ GWAS risk genes that are dysregulated in developing glutamatergic neurons (GNs), another population with enriched SCZ heritability. GN-specific SCZ GWAS loci DE genes converge at the ion transporter pathway, distinct from those for cINs. Disruption of the pathway gene CACNA1D resulted in deficits of Ca2+ currents in developing GNs. This study illustrates cell type-specific and developmental stage-specific mechanisms of SCZ risk gene function and may provide novel therapeutic targets (Molecular Pyschiatry, 2022).