Research in Wang Lab

Dr. Charles Wang's current research focuses on substance use disorders using prenatal exposure animal models to understand the genomic and epigenomic mechanisms underlying maternal drug exposure-induced abnormal brain development.

The overall goal of the study is to investigate the genomic and epigenomic mechanisms underlying abnormal brain development caused by prenatal e-cigarette exposure. Maternal smoking is a well-recognized public health concern associated with increased neurodevelopmental disorders and other health risks in offspring. Substantial evidence indicates various adverse effects of maternal smoking or prenatal nicotine exposure on neonatal brain development, e.g., hyperactivity, reduced cognitive performance, increased anxiety and depression, and increased susceptibility to brain injury. Growing evidence suggests that maternal e-cig use affects brain development, resulting in abnormal cortical neuronal morphology and aberrant neuro-behaviors in offspring.

Wang research Loma Linda

Using a rat prenatal e-cig exposure model and single-nucleus sequencing, we recently found that prenatal e-cig exposure disrupted excitatory-inhibitory (E/I) balance, ratio of excitatory/ inhibitory neurons, in the neonatal brain. E/I balance is crucial for normal brain development and functions, and its disruption has been postulated to underlie the pathogenesis of many neurodevelopmental disorders, including autism spectrum disorders, ADHD, and other psychiatric disorders. However, the underlying genomic and epigenomic mechanisms are still not known. This investigation seeks to fill this knowledge gap.

Wang research Loma Linda

Our hypothesis is that prenatal e-cig exposure induces epigenomic reprogramming and genomic alterations in the developing brain, which cause an E/I imbalance and consequently an increased risk for neurodevelopmental disorders. Exploiting the prenatal e-cig exposure model developed, we intend to achieve three objectives. Aim 1 is to determine the spatial-temporal effects of prenatal e-cig exposure on brain development and progression of E/I imbalance using spatial genomics and single-cell sequencing techniques. Aim 2 is to determine the epigenomic mechanisms regulating the prenatal e-cig induced E/I imbalance. Aim 3 is to investigate whether prenatal e-cig causes genomic alterations (i.e., SNVs and CNVs) that are involved in E/I imbalance. This project is funded by NIH under the NIDA Animal Genomics Consortium. Many cutting-edge genomic and epigenomic technologies are exploited in our studies, including spatial genomics, single-nucleus RNA-seq and chromatin accessibility (snATAC-seq), and state-of-the-art bioinformatics tools. We expect that this study will provide valuable new insights into the effects of e-cig on the early central nervous system development, which will help explore promising molecular and cellular therapeutic targets for treating e-cig vaping-induced brain damage.

There are many other projects currently supported by Loma Linda University School of Medicine's Center for Genomics involving in genomics, epigenomics, single-cell sequencing and bioinformatics in collaborating with many different investigators at Loma Linda University, including cancer genomics and clinical genomics.